Human Reproduction, Vol. 16, No. 10, 2061-2065,
October 2001
© 2001 European Society of Human Reproduction and Embryology
Effects of androstenedione, insulin and luteinizing hormone on steroidogenesis in human granulosa luteal cells
1 Department of Gynaecology and Obstetrics, 2 Medical Department M (Endocrinology and Diabetes) and 3 Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Denmark
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 µIU/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). CONCLUSION: 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.
Key words: androgen/granulosa cell/insulin/polycystic ovary syndrome (PCOS)/steroidogenesis
4 To whom correspondence should be addressed at: Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Norrebrogade 44 DK-8000 Aarhus C, Denmark. E-mail: jg{at}farm.au.dk
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