Endogenous nitric oxide inhibits growth hormone secretion through cyclic guanosine monophosphate-dependent mechanisms in GH(3) cells

Constitutive nitric oxide synthase (NOS) is expressed in rat adenohypophysi s and clonal GH(3) cells. The mechanisms of action of nitric oxide (NO) to inhibit hormone secretion and the possible role of (6R)-5, 6, 7, 8-tetrahyd ro-L-biopterin (THB) in the action of endogenous NO were studied in GH(3) c ells. Inhibiting NOS with NO-nitro-L-arginine or trapping NO with oxyhemogl obin enhanced both the basal and TRH-stimulated rat GH release. Sodium nitr oprusside did not further decrease either the basal or the TRH-stimulated G H secretion, suggesting that endogenous NO exerted the maximal inhibitory e ffect. Inhibition of de novo synthesis of THE increased GH secretion. A cyc lic guanosine-monophosphate (cGMP) antagonist did not increase the basal GH secretion but enhanced TRH-induced GH release. These findings suggest that endogenous NO plays an inhibitory role on basal GH release and TRH-stimula ted hormone release from GH(3) cells in an autocrine or paracrine fashion, at least partly, through a cGMP-dependent pathway. It is also suggested tha t endogenous THE plays a role in NO production and subsequent inhibition of hormone secretion in GH(3) cells.