Involvement of Endogneous Nitric Oxide in the Control of Pituitary Responsiveness to Different Elicitors of Growth Hormone Release in Prepubertal Rats

Recently, nitric oxide (NO) has emerged as an important modulator of several neuroendocrine events. Present studies were designed in order to evaluate the involvement of endogenous NO in the control of GH secretion. In a first set of experiments, in vivo pituitary responsiveness to the elicitors of GH release, GH-releasing hormone (GHRH), GH-releasing hexapeptide (GHRP-6) and the agonist of excitatory amino acid receptors, N-methyl-D-aspartate (NMDA) was tested in prepubertal male rats after blockade of endogenous NO by pretreatment (45 min before the tests) with the competitive NO synthase (NOS) inhibitors NW-nitro-L-arginine methyl ester (NAME) and NW-nitro-L-arginine (NA). In addition, simultaneous administration of NAME and GHRH to prepubertal males was performed and the effects of NO deprivation on GHRH- and NMDA-stimulated GH release in prepubertal female rats were studied. In a second set of experiments, the involvement of NO in the modulation of GH secretion was analyzed in vitro. GH release by dispersed adenohypophysial cells was evaluated after challenge with the NO donors, sodium nitroprusside (SNP) and S-nitrosoacetylpenicillamine (SNAP), and cGMP, the classical second messenger for NO actions. In addition, the ability of NAME, SNP and cGMP to affect the GHRH-induced GH release in vitro was also tested. Our results showed that endogenous NO deprivation significantly attenuated in vivo GHRH-, GHRP-6- and NMDA-induced GH secretion in prepubertal male rats. However, the releasing ability of GHRH was not abolished by simultaneous administration of NAME. In addition, pretreatment with NAME blunted GHRH- and NMDA-stimulated GH release in prepubertal females. In vitro, neither SNP, SNAP, NAME nor cGMP modified GH secretion by pituitary cells in culture but NO deprivation by NAME completely blocked GHRH-induced GH release. In addition, cGMP but not SNP slightly enhanced GHRH-stimulated GH secretion. Taken together, these data strongly suggest that endogenous NO plays a permissive role in the control of stimulated GH release and that endogenous NO is an important factor eliciting GH secretion in prepubertal rats.