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 control of LH secretion and in the modulation of LH responses after stimulation with luteinizing hormone releasing hormone (LHRH), excitatory amino acids (EAAs) and leptin. The regulatory action of NO in the control of LH secretion includes modulation of LHRH release, changes in hypothalamic-pituitary blood flow and direct effects at pituitary level. To determine the net balance of these actions we evaluated (1) the effects of systemic administration of sodium nitroprusside (SNP, a NO donor) and Nw-nitro-L-arginine methyl ester (NAME, a blocker of NO synthase) on basal and LHRH-stimulated LH secretion in intact and ovariectomized females; and (2) the effects of SNP and NAME on LH secreted by dispersed pituitary cells. Finally, since NO is involved in the stimulatory effect of excitatory amino acids (EAAs) on LH secretion, we analyzed the effects of different inhibitors of NO synthase (NOS) in the LH response to kainic acid (KA), an agonist of kainate receptors, in male and female rats, neonatally injected with estradiol that show an increased 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 level, since the basal and LHRH-stimulated LH release remained unchanged in presence of NAME. Similarly, basal and LHRH-stimulated LH secretion from dispersed pituitary cells were unaffected by NAME. Finally, the stimulatory effects of KA on LH release were not abolished by NOS inhibitors. In conclusion, our results provide evidence that the global action of NOS inhibitors is an increase in basal LH secretion, through a mechanism that remains to be fully characterized. In addition, our data demonstrate that the KA-stimulated LH secretion is not mediated by an increase in NO generation.