Effects of androstenedione, insulin and luteinizing hormone on steroidogenesis in human granulosa luteal cells.
BACKGROUND
The present study was conducted to investigate the effect of androstenedione, insulin and LH on human granulosa cell oestrogen and progesterone production. We postulated that elevated concentrations of androstenedione, insulin and LH may be important modulators of granulosa cell steroidogenesis.


METHODS
Granulosa cells obtained in connection with IVF procedures were cultured for a total of 4 days in serum-free medium containing androstenedione (10(-6) mol/l). We tested the effect of androstenedione (10(-5) mol/l) on insulin (0-800 microIU/ml), LH (1-10 ng/ml) as well as on insulin + LH-stimulated oestrogen and progesterone production.


RESULTS
Insulin increased the basal secretion of steroid hormones, and furthermore augmented LH-stimulated oestrogen and progesterone accumulation in granulosa cell cultures. Androstenedione (10(-5) mol/l) stimulated basal oestrogen production, but significantly reduced (32-58%) insulin + LH-stimulated oestrogen and progesterone secretion (P < 0.05).


CONCLUSIONS
These results suggest that high androstenedione concentrations may act directly to impair insulin augmentation of LH-stimulated oestradiol and progesterone production in cultured human granulosa luteal cells. This is compatible with the hypothesis that high androgen levels may inhibit oestrogen production in polycystic ovary follicles, and as such may contribute to anovulation and infertility in women with polycystic ovary syndrome.
Greisen
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S
Department of Gynaecology and Obstetrics, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. jg@farm.au.dk
Ledet
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Ovesen
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D000735:Androstenedione / Q000494:pharmacology*; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis*
D004967:Estrogens; D007328:Insulin; D000735:Androstenedione; D011374:Progesterone; D007986:Luteinizing Hormone