Differential effects of castration and testosterone replacement on basal and LHRH-stimulated cAMP and cGMP accumulation and on gonadotropin release from the pituitary of the male rat.

Castration of male rats decreased cAMP levels, and increased cGMP levels and gonadotropin release from anterior pituitaries incubated in vitro. Testosterone (T) replacement via silastic tubes filled with the steroid increased cAMP and decreased cGMP levels and gonadotropin release. Incubation of hemipituitaries from intact males with luteinizing hormone releasing hormone (LHRH, 5 nM for 2 h) resulted in increased cAMP and cGMP accumulation and gonadotropin release. Castration abolished LHRH-induced cAMP accumulation, but increased the effect of LHRH on cGMP accumulation and gonadotropin release. Testosterone replacement restored cAMP stimulation by LHRH but decreased LHRH-induced elevation of cGMP levels and gonadotropin release. These data illustrate parallel increases by castration of LHRH-induced cGMP accumulation and of gonadotropin release. Furthermore, these two parameters are influenced in the opposite direction by replacement therapy. These results support the concept of a role for cGMP in LHRH action as well as providing evidence of a link between the feedback action of T and cGMP in the pituitary gland.