Nitric Oxide Produced by a Novel Nitric Oxide Synthase Isoform is Necessary for Gonadotropin‐Releasing Hormone‐Induced Growth Hormone Secretion Via a cGMP‐Dependent Mechanism

Abstract

The involvement of nitric oxide (NO) in the regulation of goldfish growth hormone (GH) secretion was further characterized using primary cultures of dispersed goldfish pituitary cells. Western blots revealed the presence of an inducible nitric oxide synthase (iNOS)-like protein of approximately 120 kDa in cytosol/plasma membrane extracts. By contrast, brain NOS-immunoreactive proteins of approximately 120-140 kDa were occasionally detected in a cytoskeleton/organelle fraction but were absent from cytosol/plasma membrane extracts. The NO donor sodium nitroprusside (SNP) acutely increased GH secretion but this response was not observed in the presence of either a NO scavenger (PTIO) or a soluble guanylate cyclase inhibitor (ODQ). SNP also significantly increased the levels of cyclic (c)GMP in somatotrope-enriched cell populations. Treatments with 1400W (iNOS inhibitor), PTIO and rutin hydrate (NO scavengers) and ODQ abolished the acute GH-release response to two endogenous gonadotropin-releasing hormones (GnRH). 1400W, rutin hydrate, PTIO and ODQ alone did not significantly alter basal GH secretion. Together, these results establish that an iNOS-like peptide is constitutively present in the pituitary of the goldfish. Furthermore, these data suggest that NO, most likely through the generation of cGMP, is a necessary signal transduction component of GnRH-induced GH secretion.

Pituitary adenylate cyclase-activating polypeptide (PACAP): A regulator of the innate and acquired immune functions in juvenile fish

“…In goldfish, NOS immunoreactivity is present in pituitary somatotropes and the NOS/NO signal transduction cascade mediates gonadotropin releasing hormone-stimulated GH release [29,30]. With respect to PACAP, Ohnishi T and co-workers (2008) demonstrated that this peptide stimulated neuronal nitric oxide synthase translocation, mediated by protein kinase C and protein kinase A via the PAC1-receptor [31].…”

Neuronal nitric oxide synthase in the olfactory system, forebrain, pituitary and retina of the adult teleost Clarias batrachus

“…While NADPHd positive cells were encountered in the pituitary of swordtail (Anken and Rahmann, 1996) and 10 species of catfish (Jadhao et al, 1999), NOS expression was detected in the pituitary of O. niloticus (Bordieri et al, 2003) and in the somatotropes of goldfish pituitary (Uretsky and Chang, 2000). While NO was found to be necessary for the GnRH induced GH secretion (Uretsky et al, 2003), dopamine stimulated GH release was mediated by NO in goldfish (Mitchell et al, 2008). Several immunoreactive cells and fibers were seen in the rostral pars distalis, proximal pars distalis and pars intermedia of the pituitary gland of C. batrachus.…”

“…The hypothalamo-hypophysial system of a range of teleosts was reported to be rich in NADPHd/ NOS expression (Jadhao et al, 1999;Bordieri et al, 2003). While nNOS containing cells have been reported in the pituitary of S. multipunctatus (Jadhao and Malz, 2003), NO is necessary for the GnRH induced GH secretion in goldfish (Uretsky et al, 2003).…”

Novel signals mediating the functions of somatostatin: The emerging role of NO/cGMP

“…In another paradigm, SRIF inhibited the NO-mediated stimulation of GH release in goldfish pituitary somatotrophs (Yunker et al, 2003).…”

“…Somatostatin was found to exert a dual role in previous studies had supported a functional role of NO in GH release (Pinilla et al, 1999, Bocca et al, 2000. NO generated cGMP was shown to be a necessary signal transduction component of GnRH-induced GH secretion (Uretsky et al, 2003). Luque et al (2005) reported that NOS/NO plays a critical role in the stimulatory actions of low concentrations of SRIF on pig GH release, but without the involvement of cGMP.…”