title: Genes and proteins of the alternative steroid backdoor pathway for dihydrotestosterone synthesis are expressed in the human ovary and seem enhanced in the polycystic ovary syndrome.
abstract: Recently, dihydrotestosterone biosynthesis through the backdoor pathway has been implicated for the human testis in addition to the classic pathway for testosterone (T) synthesis. In the human ovary, androgen precursors are crucial for estrogen synthesis and hyperandrogenism in pathologies such as the polycystic ovary syndrome is partially due to ovarian overproduction. However, a role for the backdoor pathway is only established for the testis and the adrenal, but not for the human ovary. To investigate whether the backdoor pathway exists in normal and PCOS ovaries, we performed specific gene and protein expression studies on ovarian tissues. We found aldo-keto reductases (AKR1C1-1C4), 5α-reductases (SRD5A1/2) and retinol dehydrogenase (RoDH) expressed in the human ovary, indicating that the ovary might produce dihydrotestosterone via the backdoor pathway. Immunohistochemical studies showed specific localization of these proteins to the theca cells. PCOS ovaries show enhanced expression, what may account for the hyperandrogenism.
authors.affiliation: Pediatric Endocrinology and Diabetology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Switzerland; Graduate School Bern, University of Bern, Switzerland.
authors.forename: Nesa
authors.initials: N
authors.lastname: Marti
authors.affiliation: Institute of Pathology, University of Bern, Switzerland.
authors.forename: José A
authors.initials: JA
authors.lastname: Galván
authors.affiliation: Pediatric Endocrinology and Diabetology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Amit V
authors.initials: AV
authors.lastname: Pandey
authors.affiliation: Institute of Pathology, University of Bern, Switzerland.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Trippel
authors.affiliation: Institute of Pathology, University of Bern, Switzerland.
authors.forename: Coya
authors.initials: C
authors.lastname: Tapia
authors.affiliation: Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Gynecology and Obstetrics, Inselspital, Bern University Hospital, University of Bern, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Müller
authors.affiliation: Institute of Pathology, University of Bern, Switzerland.
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.affiliation: Pediatric Endocrinology and Diabetology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, Inselspital, Bern University Hospital, University of Bern, Switzerland. Electronic address: christa.flueck@dkf.unibe.ch.
authors.forename: Christa E
authors.initials: CE
authors.lastname: Flück
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D053898:Biosynthetic Pathways / Q000235:genetics*; D002648:Child; D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D013737:Testis / Q000378:metabolism; D055815:Young Adult
chemical_list: D013196:Dihydrotestosterone
keywords: Adrenals; Androgen biosynthesis; Androgens; Classic and alternative backdoor pathway; Dihydrotestosterone; Human ovary; PCOS; Testis