Differential effects of cyclic nucleotide analogues and GnRH on LH synthesis and release

Abstract

We compared the effects of gonadotropin-releasing hormone (GnRH) and cyclic nucleotides on biosynthesis and release of luteinizing hormone (LH) by rat anterior pituitary glands (APs). APs from ovariectomized rats were incubated in the presence of test compounds, [3H]glucosamine, and [14C]alanine. GnRH significantly (P less than 0.01) increased both incorporation of [3H]glucosamine into LH (glycosylation) and release of immunoreactive LH (IR-LH) and [3H]LH. None of the cyclic nucleotides alone at 5 mM significantly stimulated release of IR-LH. Adenosine 3',5'-cyclic monophosphate (cAMP), N6,O2'-dibutyryl cAMP (DBcAMP), and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP) stimulated (P less than 0.01) glycosylation, whereas 8-Br-AMP, 8-bromoguanosine 5'-monophosphate (8-Br-GMP), cGMP, and 8-Br-cGMP had no detectable effect. Release of [3H]LH was increased by GnRH, 8-Br-cAMP, and DBcAMP, but not by other nucleotides. None of the cyclic nucleotides elevated [14C]LH, whereas GnRH elevated it (P less than 0.01) in the medium. Dose-response curves for glycosylation in response to 8-Br-cAMP and GnRH were parallel. In contrast, dose-response curves for release of both [3H]LH and IR-LH were nonparallel. It appears that cAMP can mimic the action of GnRH on LH glycosylation, but may have little direct effect on LH release.