Autoregulation of acute progesterone and adenosine 3',5'-monophosphate responses to follicle-stimulating hormone (FSH) in porcine granulosa cells: effects of FSH, cholera toxin, forskolin, and pertussis toxin.

The purpose of these studies was to determine how exposure to FSH affects subsequent responsiveness of adenylyl cyclase and progesterone production to FSH in immature porcine granulosa cells in vitro. Acute cAMP and progesterone responses to FSH and the postreceptor activators of cyclase, forskolin and cholera toxin, were determined after a 24-h preincubation with FSH. Pretreatment with FSH (1-1000 ng/ml) resulted in an increase in subsequent basal progesterone production which was dependent on preincubation FSH concentration. The cAMP response to FSH, on the other hand, was reduced after preincubation with FSH in a manner dependent on preincubation FSH concentration. Removal of FSH with acidified medium and subsequent incubation in FSH-free medium resulted in recovery of the cAMP response to FSH, indicating that attenuation of the response is reversible. Attenuation of the cAMP response to FSH does not appear to be due to 1) a loss of activity of the catalytic moiety of cyclase, since the response to forskolin and cholera toxin was not decreased by FSH; 2) a decrease in coupling of the stimulatory guanine nucleotide regulatory protein with the catalytic moiety of cyclase, since the response to cholera toxin was not reduced by FSH; 3) inhibitory signals, since preincubation with pertussis toxin did not affect the subsequent response to FSH; or 4) cAMP itself, since neither cholera toxin nor the cAMP analog 8-(4-chlorophenyl-thio)cAMP affected the response to FSH. It appears, instead, that FSH regulates FSH responsiveness by regulating the interaction of the FSH receptor with stimulatory guanine nucleotide regulatory protein.