METABOLIC-REGULATION OF ANDROGEN PRODUCTION BY HUMAN THECAL CELLS IN-VITRO

The association between hyperinsulinaemia and hyperandrogenism in many women with polycystic ovarian syndrome (PCOS) implies roles for insul in 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 productio n by human thecal cells in vitro, Serum-free monolayer cell cultures w ere established from the ovaries of euandrogenic women undergoing hyst erectomy with oophorectomy for non-ovarian indications, Androgen (andr ostenedione) production was determined after 4 days of culture in the presence of insulin or either of the IGFs (10-100 ng/ml), with and wit hout 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 h ormones exerted similar dose-related effects on androgen production (E D(50) less than or equal to 10 ng/ml), which were augmented 2- to 3-fo ld in the presence of LH and further increased several-fold by the add itional presence of inhibin, No treatment with insulin or either IGF s timulated thecal cell growth, but all treatments caused striking morph ological changes consistent with enhanced steroidogenesis, These resul ts reveal potent regulatory effects of metabolic hormones on human the cal 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 gr anulosa-derived IGF-II and inhibin in regulating ovarian androgen prod uction.