Endogenous nitric oxide inhibits growth hormone secretion through cyclic guanosine monophosphate-dependent mechanisms in GH3 cells.
Constitutive nitric oxide synthase (NOS) is expressed in rat adenohypophysis and clonal GH3 cells. The mechanisms of action of nitric oxide (NO) to inhibit hormone secretion and the possible role of (6R)-5, 6, 7, 8-tetrahydro-L-biopterin (THB) in the action of endogenous NO were studied in GH3 cells. Inhibiting NOS with N(G)-nitro-L-arginine or trapping NO with oxyhemoglobin enhanced both the basal and TRH-stimulated rat GH release. Sodium nitroprusside did not further decrease either the basal or the TRH-stimulated GH secretion, suggesting that endogenous NO exerted the maximal inhibitory effect. Inhibition of de novo synthesis of THB increased GH secretion. A cyclic 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-stimulated hormone release from GH3 cells in an autocrine or paracrine fashion, at least partly, through a cGMP-dependent pathway. It is also suggested that endogenous THB plays a role in NO production and subsequent inhibition of hormone secretion in GH3 cells.
Tsumori
M
M
Department of Medicine, Shimane Medical University, Izumo, Japan.
Murakami
Y
Y
Koshimura
K
K
Kato
Y
Y
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000502:physiology; D002460:Cell Line; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D004791:Enzyme Inhibitors; D010108:Oxyhemoglobins; D013873:Thionucleotides; D001708:Biopterins; D009569:Nitric Oxide; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone; C003402:sapropterin; D006152:Cyclic GMP