Involvement of nitric oxide in the regulation of gonadotropin-releasing hormone release from the GT1-1 neuronal cell line.
A role for nitric oxide (NO) in the regulation of hypothalamic neurohormone secretion has been suggested. The aim of the present study was to establish a direct involvement of this novel intracellular regulatory molecule in the control of GnRH release. For this purpose, the GT1-1 GnRH-secreting continuous cell line was treated with various agents that can modify the endogenous NO synthase activity or, alternatively, with substances that can liberate NO, mimicking an increased concentration of this molecule in the cell. Treatment of GT1-1 cells with increasing concentrations of L-arginine, the direct precursor of NO, produced a marked reduction of norepinephrine-stimulated GnRH release despite a lack of effect on basal secretion. Similarly, the NO donors SIN-1 and acidified NaNO2 potently reduced basal as well as KCl-stimulated GnRH secretion. Conversely, sodium nitroprusside caused a significant inhibition of KCl-stimulated, but not basal, GnRH secretion. Addition of these agents to GT1-1 cells resulted in a marked increase in intracellular cGMP accumulation. Addition of the NO synthase inhibitors N-nitro-L-arginine and N-nitro-L-arginine methyl ester stimulated basal GnRH secretion without modifying norepinephrine- or KCl-stimulated release. In addition, treatment of GT1-1 cells with both L-arginine analogs produced a significant inhibition of the basal cGMP concentration. Together, these data suggest an inhibitory role for NO in the control of GnRH secretion from GT1-1 cells.
Sortino
M A
MA
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Aleppo
G
G
Scapagnini
U
U
Canonico
P L
PL
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology
D009599:Nitroprusside; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D012977:Sodium Nitrite; D009638:Norepinephrine