17α-Estradiol

17β-Estradiol 17α-estradiol as a hormone its use as a medication Alfatradiol vanc Alfatradiol skeletal.svg skin-invert-image 225px Estra-1,3,5(10)-triene-3,17α-diol (1R,3aS,3bR,9bS,11aS)-11a-Methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthrene-1,7-diol 17α-E2; Alpha-Estradiol; Alfatradiol; 17-Epiestradiol; β-Estradiol (obsolete, misleading)J. Elks The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA897 14 November 2014 Springer 978-1-4757-2085-3 897– 57-91-0 61840 17160 1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17-,18+/m1/s1 68570 3VQ38D63M7 Oc1ccc2[C@H]3CC[C@]4(C)[C@@]5(CC[C@H]4[C@@H]3CCc2c1).O5 18 24 2 17α-Estradiol (also known as 17α-E2, 17-epiestradiol, alfatradiol, or estra-1,3,5(10)-triene-3,17α-diol) is a minor and weak endogenous steroidal estrogen that is related to 17β-estradiol (better known simply as estradiol). It is the C17 epimer of estradiol. It has approximately 100-fold lower estrogenic potency than 17β-estradiol.Ralph M. Trüeb Won-Soo Lee Male Alopecia: Guide to Successful Management https://books.google.com/books?id=0ue5BAAAQBAJ&pg=PA93 13 February 2014 Springer Science & Business Media 978-3-319-03233-7 93– The compound shows preferential affinity for the ERα over the ERβ. Zhu BT, Han GZ, Shim JY, Wen Y, Jiang XR Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding Endocrinology 147 9 4132–50 2006 16728493 10.1210/en.2006-0113 Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta Endocrinology 138 3 863–70 1997 9048584 10.1210/endo.138.3.4979 free Although 17α-estradiol is far weaker than 17β-estradiol as an agonist of the nuclear estrogen receptors, it has been found to bind to and activate the brain-expressed ER-X with a greater potency than that of 17β-estradiol, suggesting that it may be the predominant endogenous ligand for the receptor. Toran-Allerand CD, Tinnikov AA, Singh RJ, Nethrapalli IS 17alpha-estradiol: a brain-active estrogen? Endocrinology 146 9 3843–50 2005 15947006 10.1210/en.2004-1616 free Biosynthesis 17α-Estradiol is produced from epitestosterone by aromatase at locations not fully characterized (known to include the brain). Where and how epitestosterone is made is not fully understood. Conversion between 17α-estradiol and estrone seems to occur, but the enzymes remain unidentified. Occurrence 17α-E2 is found in mice brain, regardless of age and sex, at concentrations much higher than 17β-E2. Gonadectomized and/or adrenalectomized mice continue to have high brain levels of 17α-E2. 17α-E2 poorly binds α-fetoprotein, unlike 17β-E2. 17α-E2 is excreted in urine. It was initially discovered in pregnant mare urine (see conjugated estrogens). In a 2022 study, all six tested human urine samples contained detectable amounts of 17α-E2.Tang Z Liu ZH Wang H Dang Z 17α-Estradiol, an ignored endogenous natural estrogen in human: Updated estrogen metabolism pathways and its environmental risk analysis. The Science of the Total Environment 10 July 2022 829 154693 10.1016/j.scitotenv.2022.154693 35318059 2022ScTEn.82954693T 247579981 Function As mentioned before, 17α-estradiol binds to ERα and ERβ with moderate affinity but very low activity. It binds to the brain-localized ER-X with significant activity and may play a neuroprotective role. In the uterus, 17α-estradiol causes smooth muscle relaxation via a nongenomic pathway, similarly to 17β-estradiol; the effect is weaker with no antagonization. It antagonizes the hypertrophic response of 17β-estradiol, probably by acting as an antiestrogen by virtue of its very low activity.Perusquía M Navarrete E Evidence that 17alpha-estradiol is biologically active in the uterine tissue: antiuterotonic and antiuterotrophic action. Reproductive Biology and Endocrinology 21 July 2005 3 30 10.1186/1477-7827-3-30 16042770 1201169 free Aging Supplementation of 17α-Estradiol increases the median lifespan of male mice by 19%, it has no effect on female lifespan. 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction and improves glucose tolerance in male mice, it does not lead to feminization of male mice.Stout Michael B. Steyn Frederik J. Jurczak Michael J. Camporez Joao-Paulo G. Zhu Yi Hawse John R. Jurk Diana Palmer Allyson K. Xu Ming Pirtskhalava Tamar Evans Glenda L. de Souza Santos Roberta Frank Aaron P. White Thomas A. Monroe David G. 2016-01-24 17α-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 72 1 3–15 10.1093/gerona/glv309 1079-5006 5155656 26809497Garratt Michael Bower Brian Garcia Gonzalo G. Miller Richard A. December 2017 Sex differences in lifespan extension with acarbose and 17-α estradiol: gonadal hormones underlie male-specific improvements in glucose tolerance and mTORC 2 signaling Aging Cell en 16 6 1256–1266 10.1111/acel.12656 free 1474-9718 5676051 28834262Strong Randy Miller Richard A. Antebi Adam Astle Clinton M. Bogue Molly Denzel Martin S. Fernandez Elizabeth Flurkey Kevin Hamilton Karyn L. Lamming Dudley W. Javors Martin A. Magalhães João Pedro Martinez Paul Anthony McCord Joe M. Miller Benjamin F. October 2016 Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer Aging Cell en 15 5 872–884 10.1111/acel.12496 free 1474-9718 5013015 27312235 The exact reason for this sex-specific increase in lifespan is unknown, however, the effect on male lifespan is not visible in castrated mice. This suggests that the metabolic response to 17α-Estradiol requires the presence of male gonadal hormones.Garratt Michael Lagerborg Kim A. Tsai Yi-Miau Galecki Andrzej Jain Mohit Miller Richard A. August 2018 Male lifespan extension with 17-α estradiol is linked to a sex-specific metabolomic response modulated by gonadal hormones in mice Aging Cell en 17 4 e12786 10.1111/acel.12786 free 6052402 29806096 The effect of 17α-Estradiol on humans is currently unknown. See also List of estrogens References Category:Secondary alcohols Category:Estranes Category:Estrogens Category:Hormones of the hypothalamus-pituitary-gonad axis Category:Sex hormones