ROLE OF ANDROGENS IN FOLLICLE MATURATION AND ATRESIA

Androgens are products of progestogen metabolism intermediates in oest rogen biosynthesis and local regulators of ovarian function. Current u nderstanding of intraovarian androgen formation, metabolism and action is reviewed, highlighting the contribution of androgens to the paracr ine regulation of follicular maturation and atresia. Any factor that a lters intracellular cAMP levels is a potential modulator of granulosa cell differentiation, and hence follicular development. Androgen appea rs to modulate gonadotrophin action on granulosa cells through amplifi cation of cAMP-mediated post-receptor signalling. Here it is argued th at during intermediate stages of follicular development, locally produ ced androgen acts via granulosa cell androgen receptors (AR) to promot e follicle-stimulating hormone (FSH)-induced granulosa cell differenti ation through amplifying cAMP-mediated post-receptor signalling. Durin g late pre-ovulatory follicular development, higher concentrations of cAMP caused by stimulation with luteinizing hormone (LH) suppress gran ulosa cell proliferation and downregulate some of the genes induced by FSH at earlier stages of pre-ovulatory development, including aromata se activity. Other granulosa cell functions, including progesterone sy nthesis, are enhanced by the high concentrations of cAMP induced by LH . There is experimental evidence from studies of rat and non-human pri mate (common marmoset) ovaries that AR levels in granulosa cells decli ne during pre-ovulatory follicular maturation. Since androgens augment FSH induced cAMP formation and action, loss of AR could be a means of avoiding inappropriately high cAMP levels and hence avoiding prematur e activation of 'high-tone' cAMP-response genes that lead to atresia. Negative regulation of the granulosa cell AR could be part of the intr a-ovarian mechanism that determines which follicle(s) becomes dominant and secretes oestrogen in the normal menstrual cycle.