The role of nitric oxide in the control of basal and LHRH-stimulated LH secretion

The gaseous transmitter nitric oxide (NO) appears to be involved in the con trol of LH secretion and in the modulation of LH responses after stimulatio n with luteinizing hormone releasing hormone (LHRH), excitatory amino acids (EAAs) and leptin. The regulatory action of NO in the control of LH secret ion includes modulation of LHRH release, changes in hypothalamic-pituitary blood flow and direct effects at pituitary level. To determine the net bala nce of these actions we evaluated (1) the effects of systemic administratio n of sodium nitroprusside (SNP, a NO donor) and N-w-nitro-L-arginine methyl ester (NAME, a blocker of NO synthase) on basal and LHRH-stimulated LH sec retion in intact and ovariectomized females; and (2) the effects of SNP and NAME on LH secreted by dispersed pituitary cells. Finally, since NO is inv olved in the stimulatory effect of excitatory amino acids (EAAs) on LH secr etion, we analyzed the effects of different inhibitors of NO synthase (NOS) in the LH response to kainic acid (KA), an agonist of kainate receptors, i n male and female rats, neonatally injected with estradiol that show an inc reased sensitivity to EAAs. We found that NAME (40 and 60 mg/kg) increases LH secretion in intact and ovariectomized females, while SNP had no effect. The effect of NAME was not mediated through a direct action at pituitary l evel, since the basal and LHRH-stimulated LH release remained unchanged in presence of NAME. Similarly, basal and LHRH-stimulated LH secretion from di spersed pituitary cells were unaffected by NAME. Finally, the stimulatory e ffects of KA on LH release were not abolished by NOS inhibitors. In conclus ion, our results provide evidence that the global action of NOS inhibitors is an increase in basal LH secretion, through a mechanism that remains to b e fully characterized. In addition, our data demonstrate that the KA-stimul ated LH secretion is not mediated by an increase in NO generation. (C) 1999 , Editrice Kurtis.