Human Reproduction, Vol. 10, No. 1, pp. 75-81, 1995
© 1995 European Society of Human Reproduction and Embryology
Metabolic regulation of androgen production by human thecal cells in vitro
Reproductive Endocrinology Laboratory, Department of Obstetrics and Gynaecology, University of Edinburgh Centre for Reproductive Biology 37 Chalmers Street, Edinburgh EH3 9EW, UK
Correspondence: 1To whom correspondence should be addressed
The association between hyperinsulinaemia and hyperandrogenism in many women with polycystic ovarian syndrome (PCOS) implies roles for insulin and insulin-like growth factors (IGFs) in the regulation of ovarian androgen production. The aim of the present study was to compare the abilities of insulin, IGF-I and IGF-II to stimulate androgen production by human thecal cells in vitro. Serum-free monolayer cell cultures were established from the ovaries of euandrogenic women undergoing hysterectomy with oophorectomy for non-ovarian indications. Androgen (androstenedione) production was determined after 4 days of culture in the presence of insulin or either of the IGFs (10–100 ng/ml), with and without a maximal stimulatory dose of luteinizing hormone (LH; 10 ng/ml). Interactions with inhibin (30 ng/ml), a putative paracrine regulator of ovarian androgen synthesis, were also tested. The three metabolic hormones exerted similar dose-related effects on androgen production (ED50 
10 ng/ml), which were augmented 2- to 3-fold in the presence of LH and further increased several-fold by the additional presence of inhibin. No treatment with insulin or either IGF stimulated thecal cell growth, but all treatments caused striking morphological changes consistent with enhanced steroidogenesis. These results reveal potent regulatory effects of metabolic hormones on human thecal androgen synthesis, which imply (i) ‘progonadotrophic’ roles for insulin and IGF-I in regulating normal ovarian androgen production, (ii) a role for insulin in the aetiology of hyperandrogenism (both with and without hyperinsulinism) in PCOS and (iii) paracrine roles for granulosa-derived IGF-II and inhibin in regulating ovarian androgen production.
Key words: androgen synthesis/human thecal cells/insulin/IGF-I and II
Submitted on June 20, 1994; accepted on September 16, 1994.
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