Effect of recombinant activin on androgen synthesis in cultured human thecal cells.
The effect of activin-A on ovarian androgen synthesis was tested in vitro using serum-free monolayer cultures of human thecal cells. Maximal rates of androgen (androstenedione and dehydroepiandrosterone) production were induced by treating the cells for 4 days with LH (10 ng/mL) in the presence of insulin-like growth factor-I (greater than or equal to 30 ng/mL). The additional presence of recombinant activin-A (1-100 ng/mL) in culture medium caused dose-dependent suppression of thecal cell androgen production, with 50% maximal inhibition occurring at an activin-A concentration of about 10 ng/mL. Progesterone production was only suppressed by high dose (100 ng/mL) activin-A, and inhibition of steroid production occurred without inhibition of DNA synthesis (tritiated thymidine uptake). These results reveal a potent and selective inhibitory action of activin-A on thecal cell androgen synthesis, consistent with a paracrine function for activin(s) in modulating follicular androgen biosynthesis in the human ovary.
Hillier
S G
SG
Department of Obstetrics and Gynecology, University of Edinburgh, Scotland, United Kingdom.
Yong
E L
EL
Illingworth
P J
PJ
Baird
D T
DT
Schwall
R H
RH
Mason
A J
AJ
D028341:Activins; D000328:Adult; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000494:pharmacology; D011994:Recombinant Proteins; D013256:Steroids / Q000096:biosynthesis; D013799:Theca Cells / Q000378:metabolism*; D013936:Thymidine / Q000493:pharmacokinetics
D000728:Androgens; D011994:Recombinant Proteins; D013256:Steroids; D028341:Activins; D000735:Androstenedione; D007265:Inhibins; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D013936:Thymidine