The recent demonstration of high concentrations of 5 alpha-androstane-3,17-
dione in the follicular fluid of polycystic ovaries suggests a potential ro
le for 5 alpha-reduced androgens in the etiology of polycystic ovary syndro
me (PCOS). The purpose of the present study was to determine whether there
is increased 5 alpha-reductase activity or messenger ribonucleic acid (mRNA
) expression in polycystic ovaries. 5 alpha-Reductase 1 and Ein-reductase 2
mRNAs were measured in thecal (TC) and granulosa (GC) cells from individua
l follicles of 18 women with PCOS and 26 regularly cycling control women. B
oth Soc-reductase 1 and 2 mRNA expression was higher in GC than in TC, and
5 alpha-reductase 2 mRNA levels were approximately 3-fold higher than 5 alp
ha-reductase 1 mRNA. 5 alpha-Reductase I and 2 mRNA expression were similar
in GC from PCOS and control women, but 5 alpha-reductase mRNA was decrease
d in TC from PCOS follicles. In control women, 5 alpha-reductase 2 mRNA was
highest in GC from 3- to 5-mm follicles and decreased to undetectable leve
ls in GC from 7-mm follicles. A similar pattern of expression was present i
n GC from PCOS follicles, but detectable levels of 5 alpha-reductase 2 mRNA
were present in GC from. 7-mm follicles. 5 alpha-Reductase activity was me
asured in whole follicles by measuring the conversion of radiolabeled testo
sterone to dihydrotestosterone. Kinetic analysis of total 5 alpha-reductase
activity at physiological pH revealed a K-m of 1.46 mu mol/L and a maximal
velocity of 0.31 nmol/min.mg protein, indicating predominantly type 1 acti
vity. The total Sol-reductase activity was approximately 4-fold higher in P
COS follicles than in control follicles. These data demonstrate elevated 5
alpha-reductase activity in polycystic ovaries and support the hypothesis t
hat 5 alpha-reduced androgens may play a role in the pathogenesis of PCOS.