Effects of GnRH and drugs that affect cAMP levels on LH synthesis and release.

We examined basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release and synthesis in response to drugs that raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. Anterior pituitaries from ovariectomized rats were incubated with or without drugs in the presence of GnRH and [3H]glucosamine. Neither 8-bromo-cAMP (8-Br-cAMP) (10 mM), cholera toxin (10 micrograms/ml), nor phosphodiesterase inhibitors [theophylline, 2 and 8 mM; 3-isobutyl-1-methylxanthine (MIX), 0.2 mM] had any detectable effect on release of immunoreactive LH (IR-LH) when used alone. However, 8-Br-cAMP and the inhibitors potentiated (P less than 0.01) GnRH-induced release of IR-LH. Total radiolabeled LH in the system was elevated (P less than 0.01) by either GnRH, 8-Br-cAMP for cholera toxin, but reduced (P less than 0.01) by 8 mM theophylline and unaffected by MIX or 2 mM theophylline. 8-Br-cAMP did not alter the effect of GnRH on radiolabeled LH in the total system, whereas MIX and 2 mM theophylline reduced (P less than 0.05) it. These results suggest that 1) cAMP does not effect LH release directly, but may interact with GnRH to potentiate it, 2) GnRH and cAMP have a similar mode of action on LH glycosylation, and 3) phosphodiesterase inhibitors have additional actions that interfere with LH glycosylation.