5alpha-reductase activity in women with polycystic ovary syndrome.
The recent demonstration of high concentrations of 5alpha-androstane-3,17-dione in the follicular fluid of polycystic ovaries suggests a potential role for 5alpha-reduced androgens in the etiology of polycystic ovary syndrome (PCOS). The purpose of the present study was to determine whether there is increased 5alpha-reductase activity or messenger ribonucleic acid (mRNA) expression in polycystic ovaries. 5alpha-Reductase 1 and 5alpha-reductase 2 mRNAs were measured in thecal (TC) and granulosa (GC) cells from individual follicles of 18 women with PCOS and 26 regularly cycling control women. Both 5alpha-reductase 1 and 2 mRNA expression was higher in GC than in TC, and 5alpha-reductase 2 mRNA levels were approximately 3-fold higher than 5alpha-reductase 1 mRNA. 5alpha-Reductase 1 and 2 mRNA expression were similar in GC from PCOS and control women, but 5alpha-reductase mRNA was decreased in TC from PCOS follicles. In control women, 5alpha-reductase 2 mRNA was highest in GC from 3- to 5-mm follicles and decreased to undetectable levels in GC from 7-mm follicles. A similar pattern of expression was present in GC from PCOS follicles, but detectable levels of 5alpha-reductase 2 mRNA were present in GC from 7-mm follicles. 5alpha-Reductase activity was measured in whole follicles by measuring the conversion of radiolabeled testosterone to dihydrotestosterone. Kinetic analysis of total 5alpha-reductase activity at physiological pH revealed a Km of 1.46 micromol/L and a maximal velocity of 0.31 nmol/min x mg protein, indicating predominantly type 1 activity. The total 5alpha-reductase activity was approximately 4-fold higher in PCOS follicles than in control follicles. These data demonstrate elevated 5alpha-reductase activity in polycystic ovaries and support the hypothesis that 5alpha-reduced androgens may play a role in the pathogenesis of PCOS.
Department of Obstetrics and Gynecology, Second Clinic of Surgical Gynecology, University School of Medicine, Lublin, Poland.
A J
AJ
Jakimiuk
S R
SR
Weitsman
D A
DA
Magoffin
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006107:Granulosa Cells / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000378:metabolism; D013799:Theca Cells / Q000201:enzymology
D007527:Isoenzymes; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase