{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:21:59Z","timestamp":1790832119688,"version":"4.1.0"},"reference-count":30,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Context: Dihydrotestosterone (DHT), the primary active androgen in peripheral target tissues, is metabolized by 3\u03b1-hydroxysteroid dehydrogenase type III (3\u03b1-HSD), encoded by the AKR1C2 gene, forming 5\u03b1-androstane-3\u03b1,17\u03b2-diol (3\u03b1-diol). 3\u03b1-HSD may play a role in the pathogenesis of hirsutism.<\/jats:p><jats:p>Objectives: Our objective was to evaluate the role of 3\u03b1-HSD in hirsutism by comparing 1) tissue levels of active androgens, 2) relative gene expression of AKR1C2, and 3) activity of 3\u03b1-HSD in genital skin from normal and hirsute women.<\/jats:p><jats:p>Design: Genital skin was obtained from normal and hirsute women. After homogenization, testosterone (T) and DHT levels were quantified by conventional RIA. From isolated RNA, relative expression of AKR1C2 was determined by real-time PCR. In addition, minced genital skin was incubated with [3H]DHT, and the product, [3H]3\u03b1-diol, was quantified by radio-HPLC.<\/jats:p><jats:p>Setting: The study took place at an inner-city hospital.<\/jats:p><jats:p>Patients: Patients included women undergoing posterior colporrhaphy.<\/jats:p><jats:p>Main Outcome Measures: We assessed 1) tissue levels of T, DHT, and 3\u03b1-diol; 2) relative expression of AKR1C2; and 3) conversion ratio of [3H]3\u03b1-diol to [3H]DHT.<\/jats:p><jats:p>Results: In genital skin, tissue DHT and T concentrations in hirsute women were 1.90-fold and 1.84-fold higher than in normal women (P =0 .002 and 0.03), and relative expression of AKR1C2 mRNA was reduced approximately 7-fold (P = 0.04). Genital skin from hirsute women showed less metabolism of [3H]DHT to [3H]3\u03b1-diol (conversion ratio, 0.24 \u00b1 0.19 vs. 0.85 \u00b1 0.55, P = 0.01).<\/jats:p><jats:p>Conclusions: In genital skin of hirsute women, reduced AKR1C2 gene expression and 3\u03b1-HSD activity results in decreased DHT metabolism and elevated tissue levels of DHT. Diminished DHT metabolism may play an important role in the pathogenesis of hirsutism.<\/jats:p>","DOI":"10.1210\/jc.2007-2708","type":"journal-article","created":{"date-parts":[[2008,2,6]],"date-time":"2008-02-06T02:08:51Z","timestamp":1202263731000},"page":"1298-1303","source":"Crossref","is-referenced-by-count":11,"title":["3\u03b1-Hydroxysteroid Dehydrogenase Type III Deficiency: A Novel Mechanism for Hirsutism"],"prefix":"10.1210","volume":"93","author":[{"given":"Anne Z.","family":"Steiner","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology (A.Z.S.), University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"Chang","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology (L.C., R.J.P., F.Z.S.), University of Southern California Keck School of Medicine, Los Angeles, California 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ji","sequence":"additional","affiliation":[{"name":"Medicine (Q.J., M.O., A.S.), University of Southern California Keck School of Medicine, Los Angeles, California 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murad","family":"Ookhtens","sequence":"additional","affiliation":[{"name":"Medicine (Q.J., M.O., A.S.), University of Southern California Keck School of Medicine, Los Angeles, California 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Stolz","sequence":"additional","affiliation":[{"name":"Medicine (Q.J., M.O., A.S.), University of Southern California Keck School of Medicine, Los Angeles, California 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Paulson","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology (L.C., R.J.P., F.Z.S.), University of Southern California Keck School of Medicine, Los Angeles, California 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Z.","family":"Stanczyk","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology (L.C., R.J.P., F.Z.S.), University of Southern California Keck School of Medicine, Los Angeles, California 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071618050776700_R1","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1210\/jcem-21-11-1440","article-title":"Clinical assessment of body hair growth in women.","volume":"21","author":"Ferriman","year":"1961","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618050776700_R2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0140-6736(64)92789-8","article-title":"The prevalence of \u201chirsutism\u201d in young women.","volume":"1","author":"McKnight","year":"1964","journal-title":"Lancet"},{"key":"2020071618050776700_R3","first-page":"3078","article-title":"Prevalence of the polycystic ovarian syndrome in unselected black and white women in the Southeastern United States: a prospective Study.","volume":"83","author":"Knochenhauer","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618050776700_R4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0300-595X(86)80028-7","article-title":"Hair follicles and associated glands as androgen targets.","volume":"15","author":"Ebling","year":"1986","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618050776700_R5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1365-2265.1994.tb02483.x","article-title":"Androgens and human hair growth.","volume":"40","author":"Randall","year":"1994","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071618050776700_R6","first-page":"354","article-title":"Should androgen levels be measured in hirsute women with normal menstrual cycles?","volume":"37","author":"Mehta","year":"1992","journal-title":"Int J Fertil"},{"key":"2020071618050776700_R7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0300-595X(86)80027-5","article-title":"Regulation of androgen receptor and 5\u03b1-reductase in skin of normal and hirsute women.","volume":"15","author":"Mauvis-Jarvis","year":"1986","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618050776700_R8","doi-asserted-by":"crossref","first-page":"16249","DOI":"10.1016\/S0021-9258(18)71614-1","article-title":"Expression cloning and regulation of steroid 5\u03b1-reductase, an enzyme essential for male sexual differentiation.","volume":"264","author":"Andersson","year":"1989","journal-title":"J Biol Chem"},{"key":"2020071618050776700_R9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1042\/bj3510067","article-title":"Human 3\u03b1-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto-reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones.","volume":"351","author":"Penning","year":"2000","journal-title":"Biochem J"},{"key":"2020071618050776700_R10","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mce.2003.11.006","article-title":"Structure-function of human 3\u03b1-hydroxysteroid dehydogenases: genes and proteins.","volume":"215","author":"Penning","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"2020071618050776700_R11","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/0002-9378(81)90746-8","article-title":"Hirsutism: Implications, etiology, and management.","volume":"140","author":"Hatch","year":"1981","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618050776700_R12","first-page":"165","author":"Goebelsmann","year":"1979"},{"key":"2020071618050776700_R13","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1210\/jcem-60-2-349","article-title":"5\u03b1-Reductase activity in the genital skin of hirsute women.","volume":"60","author":"Serafini","year":"1985","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618050776700_R14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/pros.10192","article-title":"Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism.","volume":"54","author":"Ji","year":"2003","journal-title":"Prostate"},{"key":"2020071618050776700_R15","doi-asserted-by":"crossref","first-page":"7610","DOI":"10.1158\/0008-5472.CAN-04-1608","article-title":"Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling.","volume":"64","author":"Ji","year":"2004","journal-title":"Cancer Res"},{"key":"2020071618050776700_R16","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1210\/endo.137.7.8770889","article-title":"Inhibition of 5\u03b1-reductase activity impairs the testosterone-dependent restoration of spermiogenesis in adult rats.","volume":"137","author":"O\u2019Donnell","year":"1996","journal-title":"Endocrinology"},{"key":"2020071618050776700_R17","first-page":"708","article-title":"Synthesis and metabolism of corticosteroids","author":"White","year":"2001","journal-title":"In: Becker KL, ed. Principles and practice of endocrinology and metabolism. 3rd ed. Philadelphia: Lippincott Williams, Wilkins;"},{"key":"2020071618050776700_R18","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1172\/JCI108402","article-title":"Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.","volume":"57","author":"Griffin","year":"1976","journal-title":"J Clin Invest"},{"key":"2020071618050776700_R19","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/0022-4731(81)90209-0","article-title":"Comparison of methyltrienolone and dihydrotestosterone binding and metabolism in human genital skin fibroblasts.","volume":"14","author":"Brown","year":"1981","journal-title":"J Steroid Biochem"},{"key":"2020071618050776700_R20","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1172\/JCI110558","article-title":"3\u03b1,17\u03b2-Androstanediol glucronide in plasma.","volume":"69","author":"Horton","year":"1982","journal-title":"J Clin Invest"},{"key":"2020071618050776700_R21","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1210\/jcem-65-4-711","article-title":"Production of 3\u03b1-androstanediol glucuronide in human genital skin.","volume":"65","author":"Lobo","year":"1987","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618050776700_R22","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0015-0282(16)57848-0","article-title":"Metabolism of dihydrotestosterone to 5\u03b1-androstane-3\u03b1,17\u03b2-diol glucuronide is greater in the peripheral compartment than in the splachnic compartment.","volume":"64","author":"Duffy","year":"1995","journal-title":"Fertil Steril"},{"key":"2020071618050776700_R23","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3109\/09513599509160449","article-title":"Time-dependent changes in serum 3\u03b1-androstanediol glucuronide correlate with hirsutism scores after ovarian suppression.","volume":"9","author":"Carmina","year":"1995","journal-title":"Gynecol Endocrinol"},{"key":"2020071618050776700_R24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1042\/bj3340399","article-title":"Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.","volume":"334","author":"Shiraishi","year":"1998","journal-title":"Biochem J"},{"key":"2020071618050776700_R25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0014-5793(84)80975-8","article-title":"Identification and purification of a 36 kDa bile acid binder in human hepatic cytosol.","volume":"177","author":"Stolz","year":"1984","journal-title":"FEBS Lett"},{"key":"2020071618050776700_R26","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1210\/en.2002-0032","article-title":"Human type 3 3\u03b1-hydroxysteroid dehydrogenase (AKR1C2) and androgen metabolism in prostate cells.","volume":"144","author":"Rizner","year":"2003","journal-title":"Endocrinology"},{"key":"2020071618050776700_R27","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0015-0282(16)48320-2","article-title":"Increased 5\u03b1-reductase activity in idiopathic hirsutism.","volume":"43","author":"Serafini","year":"1985","journal-title":"Fertil Steril"},{"key":"2020071618050776700_R28","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1365-2230.2006.02146.x","article-title":"Content of 5-\u03b1-redutase (type 1 and type 2) mRNA in dermal papillae from the lower abdominal region in women with hirsutism.","volume":"31","author":"Skalba","year":"2005","journal-title":"Exp Dermatol"},{"key":"2020071618050776700_R29","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1210\/jc.2006-0227","article-title":"Variants in the 5\u03b1-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women.","volume":"91","author":"Goodarzi","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618050776700_R30","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/S0015-0282(16)54290-3","article-title":"Serum androsterone conjugates differentiate between acne and hirsutism in hyperandrogenic women.","volume":"55","author":"Carmina","year":"1991","journal-title":"Fertil Steril"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/4\/1298\/9056679\/jcem1298.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/4\/1298\/9056679\/jcem1298.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T11:28:41Z","timestamp":1630668521000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/93\/4\/1298\/2826512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4,1]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2008,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2007-2708","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,1]]}}}