Alfatradiol (17α-estradiol) - Revision history

Dmitry Dzhagarov at 18:49, 14 March 2023

2023-03-14T18:49:37Z

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	[[File:17alpha-Estradiol.jpg\|thumb\|~~Alfatradiol (17α-estradiol)]]~~		[[File:17alpha-Estradiol.jpg\|thumb\|
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	! Alfatradiol (17α-estradiol)		! Alfatradiol (17α-estradiol)
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	\| Molar mass: 272.388 g·mol−1		\| Molar mass: 272.388 g·mol−1
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	Alfatradiol, also known as 17α-estradiol (17α-E2), is a naturally occurring enantiomer of 17β-estradiol which differs in stereochemistry at the 17th carbon atom. Unlike other exogenous estrogens, alfatradiol is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol.<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 ] </ref>		'''Alfatradiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol which differs in stereochemistry at the 17th carbon atom. Unlike other exogenous estrogens, alfatradiol is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol.<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 ] </ref>

	17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X.<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), [tel:3843-3850 3843-3850]. </ref> Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders.<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), [tel:10365-10381 10365-10381].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 </ref>		17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X.<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), [tel:3843-3850 3843-3850]. </ref> Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders.<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), [tel:10365-10381 10365-10381].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 </ref>
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	== References ==		== References ==

	~~[[Category:Drugs]]~~
	<references />		<references />
	[[Category:Main list]]		[[Category:Main list]]
			[[Category:Drugs]]

Andrea at 11:15, 27 December 2022

2022-12-27T11:15:53Z

← Older revision		Revision as of 11:15, 27 December 2022
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Andrea: category change

2022-12-27T09:36:17Z

category change

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	~~[[Category:Longevity]]~~

Andrea: /* Effects on health and lifespan */

2022-12-21T02:36:16Z

Effects on health and lifespan

← Older revision		Revision as of 02:36, 21 December 2022
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	Alfatradiol, also known as 17α-estradiol (17α-E2), is a naturally occurring enantiomer of 17β-estradiol which differs in stereochemistry at the 17th carbon atom. Unlike other exogenous estrogens, alfatradiol is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol.<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 ] </ref>		Alfatradiol, also known as 17α-estradiol (17α-E2), is a naturally occurring enantiomer of 17β-estradiol which differs in stereochemistry at the 17th carbon atom. Unlike other exogenous estrogens, alfatradiol is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol.<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 ] </ref>

	17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X.<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), 3843-3850. </ref> Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders.<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), 10365-10381.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 </ref>		17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X.<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), [tel:3843-3850 3843-3850]. </ref> Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders.<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), [tel:10365-10381 10365-10381].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 </ref>

	=== Mechanism of action ===		=== Mechanism of action ===
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	Aging is associated to an increase in visceral adiposity, [[Metabolic flexibility\|metabolic disorders]] and chronic inflammation. In this context, alfatradiol might be a useful therapeutic agent. Animal studies have shown that administration of 17α-E2 has anti-inflammatory effects and can reduce body weight,<ref name="Stout" /> leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance.<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101</ref>		Aging is associated to an increase in visceral adiposity, [[Metabolic flexibility\|metabolic disorders]] and chronic inflammation. In this context, alfatradiol might be a useful therapeutic agent. Animal studies have shown that administration of 17α-E2 has anti-inflammatory effects and can reduce body weight,<ref name="Stout" /> leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance.<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101</ref>

	Other studies have shown that alfatradiol leads to the production of hepatic insulin-like growth factor (IGF1) in male mice only, and can extend male lifespan by an average of 19% and a maximum of 7% when starting therapy from 16 months, but has no effect in the lifespan of females.<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135004 </ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013015 </ref><ref name=":0">Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052402 ] </ref><ref name=":1">Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087270 </ref> When administered to elderly male mice (but not females or neutered males), it improved physical performance and age-related sarcopenia by increasing muscle mass and improving motor coordination.<ref name=":2">Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413653</ref>		Other studies have shown that alfatradiol leads to the production of hepatic insulin-like growth factor (IGF1) in male mice only, and can extend male lifespan by an average of 7% and a maximum of 19% when starting therapy from 16 months, but has no effect in the lifespan of females.<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135004 </ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013015 </ref><ref name=":0">Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052402 ] </ref><ref name=":1">Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087270 </ref> When administered to elderly male mice (but not females or neutered males), it improved physical performance and age-related sarcopenia by increasing muscle mass and improving motor coordination.<ref name=":2">Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413653</ref>

	Topical treatment with 17α-estradiol was also found to reduce androgenic hair loss in women, though it does not seem to be effective for growing new hair and this is currently its only medical use.<ref>Orfanos, C.E., and L. Vogels. “Lokaltherapie Der Alopecia Androgenetica Mit 17α-Östradiol.” ''Dermatology'', vol. 161, no. 2, 1980, pp. 124–132., <nowiki>https://doi.org/10.1159/000250344</nowiki>. </ref>		Topical treatment with 17α-estradiol was also found to reduce androgenic hair loss in women, though it does not seem to be effective for growing new hair and this is currently its only medical use.<ref>Orfanos, C.E., and L. Vogels. “Lokaltherapie Der Alopecia Androgenetica Mit 17α-Östradiol.” ''Dermatology'', vol. 161, no. 2, 1980, pp. 124–132., <nowiki>https://doi.org/10.1159/000250344</nowiki>. </ref>

Andrea: Edited references, added context and organised content in paragraphs

2022-10-27T13:42:54Z

Edited references, added context and organised content in paragraphs

Show changes

Andrea: added to main category

2022-10-11T10:16:45Z

added to main category

← Older revision		Revision as of 10:16, 11 October 2022
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	[[Category:Drugs]]		[[Category:Drugs]]
			<references />
			[[Category:Longevity]]

Dmitry Dzhagarov at 18:51, 9 October 2022

2022-10-09T18:51:00Z

← Older revision		Revision as of 18:51, 9 October 2022
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	'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.{{PMID\|9071738}} https://doi.org/10.1016/s0039-128x(96)00242-5</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. {{PMID\|21111714}} [~~https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 PMC3048764] https~~://doi.org/10.1016/j.brainres.2010.11.058</ref>. 17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol~~: a brain-active estrogen?~~. ~~Endocrinology, 146(9), 3843-3850. {{PMID~~\|15947006}} https://doi.org/10.1210/en.2004-1616</ref>. Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (~~2021). Endolysosome localization of ERα is involved in the protective effect of~~ 17α-estradiol ~~against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50~~)~~, 10365-10381. {~~{~~PMID~~\|~~34764157}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 PMC8672688] https://doi.org/10.1523/JNEUROSCI.1475-21.2021</ref>.~~		[[File:17alpha-Estradiol.jpg\|thumb\|Alfatradiol (17α-estradiol)]]
			{\| class="wikitable"

	~~Animal studies have shown that administration of 17α~~-~~E2 rapidly reduces body weight and treats obesity<ref name="Stout">Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. P. G., Zhu, Y., Hawse, J. R., … & Kirkland, J. L.~~ (~~2017).~~ 17α-~~Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(1~~)~~, 3~~-~~15. {{PMID~~\|26809497}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155656 PMC5155656] https://doi.org/10.1093/gerona/glv309</ref>, leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance<ref name=~~"Mann">Mann~~, S~~. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal~~, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. {{PMID\|33289482}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101 PMC7744101] https://doi.org/10.7554/eLife.59616</ref>. In addition, ~~17α-E2 increases the production of insulin-like growth factor IGF1 in male mice, but does not affect the production of IGF1 in female mice, and therefore~~ '''~~apparently prolongs the life of males by an average of 19% and a maximum of 7% when starting therapy from 16 months~~'''~~, but does not affect on the life span of females<ref>Harrison, D. E., Strong,~~ R., ~~Reifsnyder~~, P., ~~Kumar~~, N., ~~Fernandez~~, E., ~~Flurkey~~, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328. {{PMID\|33788371}} [~~https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135004 PMC8135004~~] ~~https://doi.org/10.1111/acel.13328</ref><ref>Strong~~, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. {{PMID\|~~27312235}} [https~~:~~//www.ncbi.nlm.nih.gov/pmc/articles/PMC5013015 PMC5013015]~~ ~~https://doi.org/10.1111/acel.12496</ref><ref>Garratt~~, M., ~~Lagerborg~~, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. {{PMID\|~~29806096}} [https~~://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052402 PMC6052402] https://doi.org/10.1111/acel.12786</ref><ref>Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-~~Estradiol modulates IGF1 and hepatic gene expression in a sex~~-~~specific manner~~. ~~The Journals of Gerontology: Series A, 76(5), 778—785. {{PMID~~\|~~32857104~~}~~} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087270 PMC8087270] https://doi.org/10.1093/gerona/glaa215</ref>~~		\|-
			! Alfatradiol (17α-estradiol)
			\|-
			\| IUPAC_name = (8''R'',9''S'',13''S'',14''S'',17''R'')-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[''a'']phenanthrene-3,17-diol
			\|-
			\| tradename: Avicis, Avixis, Ell-Cranell Alpha, Pantostin
			\|-
			\| CAS number: 57-91-0
			\|-
			\| Molar mass 272.388 g·mol−1
			\|}

	~~When administered to elderly male mice~~ (~~but not females or neutered males~~), it ~~improved physical performance~~, ~~reducing age~~-~~related sarcopenia by increasing muscle mass~~ and ~~improving motor coordination~~<ref>~~Garratt~~, M., ~~Leander~~, D., ~~Pifer~~, K., ~~Bower~~, B., ~~Herrera~~, J. J., ~~Day~~, S. M., ... & ~~Miller~~, ~~R. A~~. (~~2019~~). ~~17‐α~~ estradiol ~~ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males~~. ~~Aging Cell~~, 18(2), ~~e12920~~. {{PMID\|~~30740872~~}} [https://www.ncbi.nlm.nih.gov/pmc/articles/~~PMC6413653 PMC6413653~~] ~~https://doi~~.~~org~~/10.~~1111/acel~~.~~12920~~</ref>		'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.{{PMID\|9071738}} {{DOI\|10.1016/s0039-128x(96)00242-5}}</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. {{PMID\|21111714}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 ] {{DOI\|10.1016/j.brainres.2010.11.058}}</ref>. 17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), 3843-3850. {{PMID\|15947006}} {{DOI\|10.1210/en.2004-1616}}</ref>. Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), 10365-10381. {{PMID\|34764157}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 ] {{DOI\|10.1523/JNEUROSCI.1475-21.2021}}</ref>.

	The beneficial effect of 17-α estradiol on male-specific life expectancy is associated with the fact that it suppresses the age-related increase in the activity of MAPK signaling pathways involved in male inflammation processes<ref name="Wink">Wink, L., Miller, R. A., & Garcia, G. G. (2022). '''Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways''' involved in intracellular signaling and inflammation. Immunity & Ageing, 19(Article number: 8), 1-20. {{PMID\|35105357}} [https://www.ncbi.nlm.nih.gov/pmc/articles/~~PMC8805398~~ PMC8805398] ~~https://doi.org/~~10.1186/s12979-022-00264-1</ref>.		Animal studies have shown that administration of 17α-E2 rapidly reduces body weight and treats obesity<ref name="Stout">Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. P. G., Zhu, Y., Hawse, J. R., … & Kirkland, J. L. (2017). 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(1), 3-15. {{PMID\|26809497}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155656 ] {{DOI\|10.1093/gerona/glv309}}</ref>, leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. {{PMID\|33289482}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101 ] {{DOI\|10.7554/eLife.59616}}</ref>. In addition, 17α-E2 increases the production of insulin-like growth factor IGF1 in male mice, but does not affect the production of IGF1 in female mice, and therefore '''apparently prolongs the life of males by an average of 19% and a maximum of 7% when starting therapy from 16 months''', but does not affect on the life span of females<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328. {{PMID\|33788371}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135004 ] {{DOI\|10.1111/acel.13328}}</ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. {{PMID\|27312235}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013015 ] {{DOI\|10.1111/acel.12496}}</ref><ref>Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. {{PMID\|29806096}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052402 ] {{DOI: 10.1111/acel.12786}}</ref><ref>Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. {{PMID\|32857104}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087270 ] {{DOI\|10.1093/gerona/glaa215}}</ref>
	In addition, 17α-estradiol appears to protect males from age-related neuroinflammation of the hypothalamus, caused by age-related changes in the activity of the sex gonads, since that neuroinflammation are partly reversible by gonadectomy<ref>Debarba, L. K., Jayarathne, H. S., Miller, R. A., Garratt, M., & Sadagurski, M. (2022). 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy. The Journals of Gerontology: Series A, 77(1), 66-74. {{PMID\|34309657}} [https://www.ncbi.nlm.nih.gov/pmc/articles/~~PMC8751796~~ PMC8751796] ~~https://doi.org/~~10.1093/gerona/glab216</ref> The study of this phenomenon is important for the fight for longevity, since the hypothalamic-pituitary-testicular (HPT) axis plays an important role in the mechanisms of exceptional longevity in men<ref>Aleksic, S., Desai, D., Ye, K., Duran, S., Gao, T., Crandall, J., ... & Milman, S. (2022). Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity. Aging cell, e13656. {{PMID\|35770332}} [https://www.ncbi.nlm.nih.gov/pmc/articles/~~PMC9381897~~ PMC9381897] ~~https://doi.org/~~10.1111/acel.13656</ref>. It should be noted that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice<ref>Isola, J. V., Veiga, G. B., de Brito, C. R., Alvarado-Rincón, J. A., Garcia, D. N., Zanini, B. M., ... & Stout, M. B. (2022). 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience, 1-12. {{PMID\|35689785}} ~~https://doi.org/~~10.1007/s11357-022-00601-8</ref>
			When administered to elderly male mice (but not females or neutered males), it improved physical performance, reducing age-related sarcopenia by increasing muscle mass and improving motor coordination<ref>Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. {{PMID\|30740872}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413653 ] {{DOI\|10.1111/acel.12920}}</ref>

			The beneficial effect of 17-α estradiol on male-specific life expectancy is associated with the fact that it suppresses the age-related increase in the activity of MAPK signaling pathways involved in male inflammation processes<ref name="Wink">Wink, L., Miller, R. A., & Garcia, G. G. (2022). '''Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways''' involved in intracellular signaling and inflammation. Immunity & Ageing, 19(Article number: 8), 1-20. {{PMID\|35105357}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805398 ] {{DOI\|10.1186/s12979-022-00264-1}}</ref>.
			In addition, 17α-estradiol appears to protect males from age-related neuroinflammation of the hypothalamus, caused by age-related changes in the activity of the sex gonads, since that neuroinflammation are partly reversible by gonadectomy<ref>Debarba, L. K., Jayarathne, H. S., Miller, R. A., Garratt, M., & Sadagurski, M. (2022). 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy. The Journals of Gerontology: Series A, 77(1), 66-74. {{PMID\|34309657}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751796 ] {{DOI\|10.1093/gerona/glab216}}</ref> The study of this phenomenon is important for the fight for longevity, since the hypothalamic-pituitary-testicular (HPT) axis plays an important role in the mechanisms of exceptional longevity in men<ref>Aleksic, S., Desai, D., Ye, K., Duran, S., Gao, T., Crandall, J., ... & Milman, S. (2022). Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity. Aging cell, e13656. {{PMID\|35770332}} https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381897 ] {{DOI\|10.1111/acel.13656}}</ref>. It should be noted that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice<ref>Isola, J. V., Veiga, G. B., de Brito, C. R., Alvarado-Rincón, J. A., Garcia, D. N., Zanini, B. M., ... & Stout, M. B. (2022). 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience, 1-12. {{PMID\|35689785}} {{DOI\|10.1007/s11357-022-00601-8}}</ref>

	17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair and this is currently its only medical use.		17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair and this is currently its only medical use.

Dmitry Dzhagarov at 17:18, 9 October 2022

2022-10-09T17:18:28Z

← Older revision		Revision as of 17:18, 9 October 2022
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	'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.{{PMID\|9071738}} ~~{{DOI\|~~10.1016/s0039-128x(96)00242-5}}</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. {{PMID\|21111714}} ~~{{PMC\|3048764}} {{DOI\|~~10.1016/j.brainres.2010.11.058}}</ref>. 17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), 3843-3850. {{PMID\|15947006}} ~~{{DOI\|~~10.1210/en.2004-1616}}</ref>. Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), 10365-10381. {{PMID\|34764157}} ~~{{PMC\|8672688}} {{DOI\|~~10.1523/JNEUROSCI.1475-21.2021}}</ref>.		'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.{{PMID\|9071738}} https://doi.org/10.1016/s0039-128x(96)00242-5</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. {{PMID\|21111714}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 PMC3048764] https://doi.org/10.1016/j.brainres.2010.11.058</ref>. 17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), 3843-3850. {{PMID\|15947006}} https://doi.org/10.1210/en.2004-1616</ref>. Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), 10365-10381. {{PMID\|34764157}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 PMC8672688] https://doi.org/10.1523/JNEUROSCI.1475-21.2021</ref>.

	Animal studies have shown that administration of 17α-E2 rapidly reduces body weight and treats obesity<ref name="Stout">Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. P. G., Zhu, Y., Hawse, J. R., … & Kirkland, J. L. (2017). 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(1), 3-15. {{PMID\|26809497}} ~~{{PMC\|5155656}} {{DOI\|~~10.1093/gerona/glv309}}</ref>, leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. {{PMID\|33289482}} ~~{{PMC\|7744101}} {{DOI\|~~10.7554/eLife.59616}}</ref>. In addition, 17α-E2 increases the production of insulin-like growth factor IGF1 in male mice, but does not affect the production of IGF1 in female mice, and therefore '''apparently prolongs the life of males by an average of 19% and a maximum of 7% when starting therapy from 16 months''', but does not affect on the life span of females<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328. {{PMID\|33788371}} ~~{{PMC\|8135004}} {{DOI\|~~10.1111/acel.13328}}</ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. {{PMID\|27312235}} ~~{{PMC\|5013015}} {{DOI\|~~10.1111/acel.12496}}</ref><ref>Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. {{PMID\|29806096}} ~~{{PMC\|6052402}} {{DOI~~: 10.1111/acel.12786}}</ref><ref>Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. {{PMID\|32857104}} ~~{{PMC\|8087270}} {{DOI\|~~10.1093/gerona/glaa215}}</ref>		Animal studies have shown that administration of 17α-E2 rapidly reduces body weight and treats obesity<ref name="Stout">Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. P. G., Zhu, Y., Hawse, J. R., … & Kirkland, J. L. (2017). 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(1), 3-15. {{PMID\|26809497}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155656 PMC5155656] https://doi.org/10.1093/gerona/glv309</ref>, leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. {{PMID\|33289482}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101 PMC7744101] https://doi.org/10.7554/eLife.59616</ref>. In addition, 17α-E2 increases the production of insulin-like growth factor IGF1 in male mice, but does not affect the production of IGF1 in female mice, and therefore '''apparently prolongs the life of males by an average of 19% and a maximum of 7% when starting therapy from 16 months''', but does not affect on the life span of females<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328. {{PMID\|33788371}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135004 PMC8135004] https://doi.org/10.1111/acel.13328</ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. {{PMID\|27312235}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013015 PMC5013015] https://doi.org/10.1111/acel.12496</ref><ref>Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. {{PMID\|29806096}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052402 PMC6052402] https://doi.org/10.1111/acel.12786</ref><ref>Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. {{PMID\|32857104}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087270 PMC8087270] https://doi.org/10.1093/gerona/glaa215</ref>

	When administered to elderly male mice (but not females or neutered males), it improved physical performance, reducing age-related sarcopenia by increasing muscle mass and improving motor coordination<ref>Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. {{PMID\|30740872}} ~~{{PMC\|6413653}} {{DOI\|~~10.1111/acel.12920}}</ref>		When administered to elderly male mice (but not females or neutered males), it improved physical performance, reducing age-related sarcopenia by increasing muscle mass and improving motor coordination<ref>Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. {{PMID\|30740872}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413653 PMC6413653] https://doi.org/10.1111/acel.12920</ref>

	The beneficial effect of 17-α estradiol on male-specific life expectancy is associated with the fact that it suppresses the age-related increase in the activity of MAPK signaling pathways involved in male inflammation processes<ref name="Wink">Wink, L., Miller, R. A., & Garcia, G. G. (2022). '''Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways''' involved in intracellular signaling and inflammation. Immunity & Ageing, 19(Article number: 8), 1-20. {{PMID\|35105357}} ~~{{PMC\|8805398}} {{DOI\|~~10.1186/s12979-022-00264-1}}</ref>.		The beneficial effect of 17-α estradiol on male-specific life expectancy is associated with the fact that it suppresses the age-related increase in the activity of MAPK signaling pathways involved in male inflammation processes<ref name="Wink">Wink, L., Miller, R. A., & Garcia, G. G. (2022). '''Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways''' involved in intracellular signaling and inflammation. Immunity & Ageing, 19(Article number: 8), 1-20. {{PMID\|35105357}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805398 PMC8805398] https://doi.org/10.1186/s12979-022-00264-1</ref>.
	In addition, 17α-estradiol appears to protect males from age-related neuroinflammation of the hypothalamus, caused by age-related changes in the activity of the sex gonads, since that neuroinflammation are partly reversible by gonadectomy<ref>Debarba, L. K., Jayarathne, H. S., Miller, R. A., Garratt, M., & Sadagurski, M. (2022). 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy. The Journals of Gerontology: Series A, 77(1), 66-74. {{PMID\|34309657}} ~~{{PMC\|8751796}} {{DOI\|~~10.1093/gerona/glab216}}</ref> The study of this phenomenon is important for the fight for longevity, since the hypothalamic-pituitary-testicular (HPT) axis plays an important role in the mechanisms of exceptional longevity in men<ref>Aleksic, S., Desai, D., Ye, K., Duran, S., Gao, T., Crandall, J., ... & Milman, S. (2022). Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity. Aging cell, e13656. {{PMID\|35770332}} ~~{{PMC\|9381897}} {{DOI\|~~10.1111/acel.13656}}</ref>. It should be noted that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice<ref>Isola, J. V., Veiga, G. B., de Brito, C. R., Alvarado-Rincón, J. A., Garcia, D. N., Zanini, B. M., ... & Stout, M. B. (2022). 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience, 1-12. {{PMID\|35689785}} ~~{{DOI\|~~10.1007/s11357-022-00601-8}}</ref>		In addition, 17α-estradiol appears to protect males from age-related neuroinflammation of the hypothalamus, caused by age-related changes in the activity of the sex gonads, since that neuroinflammation are partly reversible by gonadectomy<ref>Debarba, L. K., Jayarathne, H. S., Miller, R. A., Garratt, M., & Sadagurski, M. (2022). 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy. The Journals of Gerontology: Series A, 77(1), 66-74. {{PMID\|34309657}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751796 PMC8751796] https://doi.org/10.1093/gerona/glab216</ref> The study of this phenomenon is important for the fight for longevity, since the hypothalamic-pituitary-testicular (HPT) axis plays an important role in the mechanisms of exceptional longevity in men<ref>Aleksic, S., Desai, D., Ye, K., Duran, S., Gao, T., Crandall, J., ... & Milman, S. (2022). Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity. Aging cell, e13656. {{PMID\|35770332}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381897 PMC9381897] https://doi.org/10.1111/acel.13656</ref>. It should be noted that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice<ref>Isola, J. V., Veiga, G. B., de Brito, C. R., Alvarado-Rincón, J. A., Garcia, D. N., Zanini, B. M., ... & Stout, M. B. (2022). 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience, 1-12. {{PMID\|35689785}} https://doi.org/10.1007/s11357-022-00601-8</ref>

	17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair and this is currently its only medical use.		17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair and this is currently its only medical use.

Dmitry Dzhagarov: Created page with "'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiolAnstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinit..."

2022-10-09T14:58:40Z

Created page with "'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinit..."

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'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.{{PMID|9071738}} {{DOI|10.1016/s0039-128x(96)00242-5}}</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. {{PMID|21111714}} {{PMC|3048764}} {{DOI|10.1016/j.brainres.2010.11.058}}</ref>. 17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), 3843-3850. {{PMID|15947006}} {{DOI|10.1210/en.2004-1616}}</ref>. Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), 10365-10381. {{PMID|34764157}} {{PMC|8672688}} {{DOI|10.1523/JNEUROSCI.1475-21.2021}}</ref>.

Animal studies have shown that administration of 17α-E2 rapidly reduces body weight and treats obesity<ref name="Stout">Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. P. G., Zhu, Y., Hawse, J. R., … & Kirkland, J. L. (2017). 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(1), 3-15. {{PMID|26809497}} {{PMC|5155656}} {{DOI|10.1093/gerona/glv309}}</ref>, leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. {{PMID|33289482}} {{PMC|7744101}} {{DOI|10.7554/eLife.59616}}</ref>. In addition, 17α-E2 increases the production of insulin-like growth factor IGF1 in male mice, but does not affect the production of IGF1 in female mice, and therefore '''apparently prolongs the life of males by an average of 19% and a maximum of 7% when starting therapy from 16 months''', but does not affect on the life span of females<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328. {{PMID|33788371}} {{PMC|8135004}} {{DOI|10.1111/acel.13328}}</ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. {{PMID|27312235}} {{PMC|5013015}} {{DOI|10.1111/acel.12496}}</ref><ref>Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. {{PMID|29806096}} {{PMC|6052402}} {{DOI: 10.1111/acel.12786}}</ref><ref>Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. {{PMID|32857104}} {{PMC|8087270}} {{DOI|10.1093/gerona/glaa215}}</ref>

When administered to elderly male mice (but not females or neutered males), it improved physical performance, reducing age-related sarcopenia by increasing muscle mass and improving motor coordination<ref>Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. {{PMID|30740872}} {{PMC|6413653}} {{DOI|10.1111/acel.12920}}</ref>

The beneficial effect of 17-α estradiol on male-specific life expectancy is associated with the fact that it suppresses the age-related increase in the activity of MAPK signaling pathways involved in male inflammation processes<ref name="Wink">Wink, L., Miller, R. A., & Garcia, G. G. (2022). '''Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways''' involved in intracellular signaling and inflammation. Immunity & Ageing, 19(Article number: 8), 1-20. {{PMID|35105357}} {{PMC|8805398}} {{DOI|10.1186/s12979-022-00264-1}}</ref>.
In addition, 17α-estradiol appears to protect males from age-related neuroinflammation of the hypothalamus, caused by age-related changes in the activity of the sex gonads, since that neuroinflammation are partly reversible by gonadectomy<ref>Debarba, L. K., Jayarathne, H. S., Miller, R. A., Garratt, M., & Sadagurski, M. (2022). 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy. The Journals of Gerontology: Series A, 77(1), 66-74. {{PMID|34309657}} {{PMC|8751796}} {{DOI|10.1093/gerona/glab216}}</ref> The study of this phenomenon is important for the fight for longevity, since the hypothalamic-pituitary-testicular (HPT) axis plays an important role in the mechanisms of exceptional longevity in men<ref>Aleksic, S., Desai, D., Ye, K., Duran, S., Gao, T., Crandall, J., ... & Milman, S. (2022). Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity. Aging cell, e13656. {{PMID|35770332}} {{PMC|9381897}} {{DOI|10.1111/acel.13656}}</ref>. It should be noted that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice<ref>Isola, J. V., Veiga, G. B., de Brito, C. R., Alvarado-Rincón, J. A., Garcia, D. N., Zanini, B. M., ... & Stout, M. B. (2022). 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience, 1-12. {{PMID|35689785}} {{DOI|10.1007/s11357-022-00601-8}}</ref>

17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair and this is currently its only medical use.

== References ==

[[Category:Drugs]]

← Older revision		Revision as of 17:18, 9 October 2022
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	'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.{{PMID\|9071738}} ~~{{DOI\|~~10.1016/s0039-128x(96)00242-5}}</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. {{PMID\|21111714}} ~~{{PMC\|3048764}} {{DOI\|~~10.1016/j.brainres.2010.11.058}}</ref>. 17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), 3843-3850. {{PMID\|15947006}} ~~{{DOI\|~~10.1210/en.2004-1616}}</ref>. Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), 10365-10381. {{PMID\|34764157}} ~~{{PMC\|8672688}} {{DOI\|~~10.1523/JNEUROSCI.1475-21.2021}}</ref>.		'''Alpharadiol''', also known as '''17α-estradiol (17α-E2)''', is a naturally occurring enantiomer of 17β-estradiol differing in stereochemistry at the 17th carbon atom. It is considered a non-feminizing estrogen because it has a significantly reduced binding affinity for the estrogen receptors compared to 17β-estradiol<ref>Anstead, G. M., Carlson, K. E., & Katzenellenbogen, J. A. (1997). The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids, 62(3), 268—303.{{PMID\|9071738}} https://doi.org/10.1016/s0039-128x(96)00242-5</ref><ref name="Perez">Yi, K. D., Perez, E., Yang, S., Liu, R., Covey, D. F., & Simpkins, J. W. (2011). The assessment of non-feminizing estrogens for use in neuroprotection. Brain research, 1379, 61-70. {{PMID\|21111714}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048764 PMC3048764] https://doi.org/10.1016/j.brainres.2010.11.058</ref>. 17α-E2 is synthesized in the brain and has a higher binding affinity for the its brain receptor ER-X<ref>Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17α-Estradiol: a brain-active estrogen?. Endocrinology, 146(9), 3843-3850. {{PMID\|15947006}} https://doi.org/10.1210/en.2004-1616</ref>. Because 17α-E2 has neuroprotective properties, it is hypothesized that it could be used as a therapeutic agent for HIV-related neurocognitive disorders<ref>Datta, G., Miller, N. M., Du, W., Geiger, J. D., Chang, S., & Chen, X. (2021). Endolysosome localization of ERα is involved in the protective effect of 17α-estradiol against HIV-1 gp120-induced neuronal injury. Journal of Neuroscience, 41(50), 10365-10381. {{PMID\|34764157}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672688 PMC8672688] https://doi.org/10.1523/JNEUROSCI.1475-21.2021</ref>.

	Animal studies have shown that administration of 17α-E2 rapidly reduces body weight and treats obesity<ref name="Stout">Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. P. G., Zhu, Y., Hawse, J. R., … & Kirkland, J. L. (2017). 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(1), 3-15. {{PMID\|26809497}} ~~{{PMC\|5155656}} {{DOI\|~~10.1093/gerona/glv309}}</ref>, leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. {{PMID\|33289482}} ~~{{PMC\|7744101}} {{DOI\|~~10.7554/eLife.59616}}</ref>. In addition, 17α-E2 increases the production of insulin-like growth factor IGF1 in male mice, but does not affect the production of IGF1 in female mice, and therefore '''apparently prolongs the life of males by an average of 19% and a maximum of 7% when starting therapy from 16 months''', but does not affect on the life span of females<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328. {{PMID\|33788371}} ~~{{PMC\|8135004}} {{DOI\|~~10.1111/acel.13328}}</ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. {{PMID\|27312235}} ~~{{PMC\|5013015}} {{DOI\|~~10.1111/acel.12496}}</ref><ref>Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. {{PMID\|29806096}} ~~{{PMC\|6052402}} {{DOI~~: 10.1111/acel.12786}}</ref><ref>Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. {{PMID\|32857104}} ~~{{PMC\|8087270}} {{DOI\|~~10.1093/gerona/glaa215}}</ref>		Animal studies have shown that administration of 17α-E2 rapidly reduces body weight and treats obesity<ref name="Stout">Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. P. G., Zhu, Y., Hawse, J. R., … & Kirkland, J. L. (2017). 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(1), 3-15. {{PMID\|26809497}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155656 PMC5155656] https://doi.org/10.1093/gerona/glv309</ref>, leading to a significant improvement in fasting insulin levels, glycated hemoglobin HbA1C and glucose tolerance<ref name="Mann">Mann, S. N., Hadad, N., Holte, M. N., Rothman, A. R., Sathiaseelan, R., Mondal, S. A., … & Stout, M. B. (2020). Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α. Elife, 9, e59616. {{PMID\|33289482}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101 PMC7744101] https://doi.org/10.7554/eLife.59616</ref>. In addition, 17α-E2 increases the production of insulin-like growth factor IGF1 in male mice, but does not affect the production of IGF1 in female mice, and therefore '''apparently prolongs the life of males by an average of 19% and a maximum of 7% when starting therapy from 16 months''', but does not affect on the life span of females<ref>Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328. {{PMID\|33788371}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135004 PMC8135004] https://doi.org/10.1111/acel.13328</ref><ref>Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … & Harrison, D. E. (2016). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer. Aging cell, 15(5), 872—884. {{PMID\|27312235}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013015 PMC5013015] https://doi.org/10.1111/acel.12496</ref><ref>Garratt, M., Lagerborg, K. A., Tsai, Y. M., Galecki, A., Jain, M., & Miller, R. A. (2018). Male lifespan extension with 17‐α estradiol is linked to a sex‐specific metabolomic response modulated by gonadal hormones in mice. Aging Cell, 17(4), e12786. {{PMID\|29806096}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052402 PMC6052402] https://doi.org/10.1111/acel.12786</ref><ref>Sidhom, S., Schneider, A., Fang, Y., McFadden, S., Darcy, J., Sathiaseelan, R., … & Stout, M. B. (2021). 17α-Estradiol modulates IGF1 and hepatic gene expression in a sex-specific manner. The Journals of Gerontology: Series A, 76(5), 778—785. {{PMID\|32857104}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087270 PMC8087270] https://doi.org/10.1093/gerona/glaa215</ref>

	When administered to elderly male mice (but not females or neutered males), it improved physical performance, reducing age-related sarcopenia by increasing muscle mass and improving motor coordination<ref>Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. {{PMID\|30740872}} ~~{{PMC\|6413653}} {{DOI\|~~10.1111/acel.12920}}</ref>		When administered to elderly male mice (but not females or neutered males), it improved physical performance, reducing age-related sarcopenia by increasing muscle mass and improving motor coordination<ref>Garratt, M., Leander, D., Pifer, K., Bower, B., Herrera, J. J., Day, S. M., ... & Miller, R. A. (2019). 17‐α estradiol ameliorates age‐associated sarcopenia and improves late‐life physical function in male mice but not in females or castrated males. Aging Cell, 18(2), e12920. {{PMID\|30740872}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413653 PMC6413653] https://doi.org/10.1111/acel.12920</ref>

	The beneficial effect of 17-α estradiol on male-specific life expectancy is associated with the fact that it suppresses the age-related increase in the activity of MAPK signaling pathways involved in male inflammation processes<ref name="Wink">Wink, L., Miller, R. A., & Garcia, G. G. (2022). '''Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways''' involved in intracellular signaling and inflammation. Immunity & Ageing, 19(Article number: 8), 1-20. {{PMID\|35105357}} ~~{{PMC\|8805398}} {{DOI\|~~10.1186/s12979-022-00264-1}}</ref>.		The beneficial effect of 17-α estradiol on male-specific life expectancy is associated with the fact that it suppresses the age-related increase in the activity of MAPK signaling pathways involved in male inflammation processes<ref name="Wink">Wink, L., Miller, R. A., & Garcia, G. G. (2022). '''Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways''' involved in intracellular signaling and inflammation. Immunity & Ageing, 19(Article number: 8), 1-20. {{PMID\|35105357}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805398 PMC8805398] https://doi.org/10.1186/s12979-022-00264-1</ref>.
	In addition, 17α-estradiol appears to protect males from age-related neuroinflammation of the hypothalamus, caused by age-related changes in the activity of the sex gonads, since that neuroinflammation are partly reversible by gonadectomy<ref>Debarba, L. K., Jayarathne, H. S., Miller, R. A., Garratt, M., & Sadagurski, M. (2022). 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy. The Journals of Gerontology: Series A, 77(1), 66-74. {{PMID\|34309657}} ~~{{PMC\|8751796}} {{DOI\|~~10.1093/gerona/glab216}}</ref> The study of this phenomenon is important for the fight for longevity, since the hypothalamic-pituitary-testicular (HPT) axis plays an important role in the mechanisms of exceptional longevity in men<ref>Aleksic, S., Desai, D., Ye, K., Duran, S., Gao, T., Crandall, J., ... & Milman, S. (2022). Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity. Aging cell, e13656. {{PMID\|35770332}} ~~{{PMC\|9381897}} {{DOI\|~~10.1111/acel.13656}}</ref>. It should be noted that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice<ref>Isola, J. V., Veiga, G. B., de Brito, C. R., Alvarado-Rincón, J. A., Garcia, D. N., Zanini, B. M., ... & Stout, M. B. (2022). 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience, 1-12. {{PMID\|35689785}} ~~{{DOI\|~~10.1007/s11357-022-00601-8}}</ref>		In addition, 17α-estradiol appears to protect males from age-related neuroinflammation of the hypothalamus, caused by age-related changes in the activity of the sex gonads, since that neuroinflammation are partly reversible by gonadectomy<ref>Debarba, L. K., Jayarathne, H. S., Miller, R. A., Garratt, M., & Sadagurski, M. (2022). 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy. The Journals of Gerontology: Series A, 77(1), 66-74. {{PMID\|34309657}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751796 PMC8751796] https://doi.org/10.1093/gerona/glab216</ref> The study of this phenomenon is important for the fight for longevity, since the hypothalamic-pituitary-testicular (HPT) axis plays an important role in the mechanisms of exceptional longevity in men<ref>Aleksic, S., Desai, D., Ye, K., Duran, S., Gao, T., Crandall, J., ... & Milman, S. (2022). Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity. Aging cell, e13656. {{PMID\|35770332}} [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381897 PMC9381897] https://doi.org/10.1111/acel.13656</ref>. It should be noted that chronic treatment with 17α-E2 at the dose most commonly employed in aging research does not adversely affect reproductive fitness in male mice<ref>Isola, J. V., Veiga, G. B., de Brito, C. R., Alvarado-Rincón, J. A., Garcia, D. N., Zanini, B. M., ... & Stout, M. B. (2022). 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs. GeroScience, 1-12. {{PMID\|35689785}} https://doi.org/10.1007/s11357-022-00601-8</ref>

	17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair and this is currently its only medical use.		17α-estradiol was found to reduce androgenic hair loss, though it was not effective at growing new hair and this is currently its only medical use.