Evidence for the involvement of guanosine 3',5'-cyclic monophosphate in the regulation of gonadotropin release.

Addition of dibutyryl adenosine 3'-5'-cyclic monophosphate (DBcAMP) or dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP; 1--6mM) to to enzymatically dispersed, overnight-cultured rat anterior pituitary cell preparations stimulated the release of gonadotropins (LH and FSH) from the cells into the incubation medium. Stimulation of gonadotropin release by DBcGMP was observed after only 10 min of incubation, whereas that caused by DBcAMP appeared at 180 min. Synthetic LHRH (2.5 X 10(-9) M) induced a small, transient increase in intracellular cAMP content (+16%, P less than 0.05, after 5 min coincubation), while levels of cGMP in the same cells were rapidly and markedly low for 2 h. The decrease in cGMP content was accompanied by a discharge of gonadotropins lasting for 2 h, which was detectable after 5 min in the case of LH and after 10 min in the case of FSH. These results strongly suggest that cGMP might be an intracellular mediator in the process of LHRH-stimulated release of gonadotropins.