Inhibition of rat follicular androgen synthesis by dibutyryl cyclic AMP

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Abstract
LH [luteinizing hormone] exerts a biphasic effect on rat follicular steroidogenesis: an initial general stimulation of steroidogenesis later followed by an inhibition of androgen and estrogen synthesis. The stimulation by LH of steoidogenesis is mediated by cAMP. This paper examines the role of cAMP in the late inhibitory phase of steroidogenesis. Pre-ovulatory follicles were isolated from PMSG [pregnant mare serum gonadotropin] treated immature rats and incubated in modified bicarbonate buffer for different time periods. The accumulation of progesterone (P), androstenedione (A), testosterone (T) and estradiol-17.beta. (E2) in the medium was measured. Addition of dibutyryl cAMP (dbcAMP, 1 mM) to the medium caused a prolonged increase in P accumulation for 10 h while A and E2 accumulation was stimulated only for 4-6 h whereafter the levels were sustained. The pattern was identical to that produced by LH (10 .mu.g/ml) in vitro. In a 2nd type of experiment follicles were pre-incubated for 6 h with or without LH or dbcAMP and then transferred for a second 2 h incubation, in the presence or absence of unlabeled 17-hydroxyprogesterone (17-OHP) or T (1 .mu.g/ml). Follicles pre-incubated in plain medium increased their formation of A and T in the presence of 17-OHP, while follicles exposed to LH or dbcAMP did not. Addition of T caused a similar increase in E2 formation in all groups (control, LH and dbcAMP). Since dbcAMP mimicked the entire response of follicular steroidogenesis normally elicited by LH, cAMP seems to be the physiologic mediator of LH, both on the early stimulatory and on the late inhibitory phase of pre-ovulatory follicular steroidogenesis.