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 neuroho rmone secretion has been suggested. The aim of the present study was t o establish a direct involvement of this novel intracellular regulator y molecule in the control of GnRH release. For this purpose, the GT1-1 GnRH-secreting continuous cell line was treated with various agents t hat can modify the endogenous NO synthase activity or, alternatively, with substances that can liberate NO, mimicking an increased concentra tion of this molecule in the cell. Treatment of GT1-1 cells with incre asing concentrations of L-arginine, the direct precursor of NO, produc ed a marked reduction of norepinephrine-stimulated GnRH release despit e a lack of effect on basal secretion. Similarly, the NO donors SIN-1 and acidified NaNO2 potently reduced basal as well as KCl-stimulated G nRH secretion. Conversely, sodium nitroprusside caused a significant i nhibition of KCl-stimulated, but not basal, GnRH secretion. Addition o f these agents to GT1-1 cells resulted in a marked increase in intrace llular cGMP accumulation. Addition of the NO synthase inhibitors N-nit ro-L-arginine and N-nitro-L-arginine methyl ester stimulated basal GnR H secretion without modifying norepinephrine- or KCl-stimulated releas e. In addition, treatment of GT1-1 cells with both L-arginine analogs produced a significant inhibition of the basal cGMP concentration. Tog ether, these data suggest an inhibitory role for NO in the control of GnRH secretion from GT1-1 cells.