Endogenous Nitric Oxide Inhibits Growth Hormone Secretion through Cyclic Guanosine Monophosphate-Dependent Mechanisms in GH3 Cells.

Tsumori, Michihiro; Murakami, Yoshio; Koshimura, Kunio; Kato, Yuzuru

doi:10.1507/endocrj.46.779

Cited by 15 publications

(10 citation statements)

References 33 publications

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“…This view is supported by in vitro studies showing that NOergic neurons play a permissive role in the medial basal hypothalamus to stimulate the release of many regulatory peptides, as corticotrophin-releasing hormone, luteinizing hormone releasing-hormone, GHRH, somatostatin and oxytocin (46). NO, however, has also been reported in some (18,47), though not all (7,48), studies to inhibit GHRH-induced GH release from rat pituitary cell cultures and to affect basal and dopamine inhibition of prolactin secretion (5).…”

Section: Discussionmentioning

confidence: 93%

Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

Rigamonti

Cella²,

Cavallera

et al. 2001

European Journal of Endocrinology

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Objective: Among the many actions of nitric oxide (NO) are those on endocrine and feeding behaviour. Based on NO involvement in the GH-releasing effect of the GH-releasing peptides (GHRPs) and the reported orexigenic activity of these compounds, we sought to evaluate the effect of the combined administration of a long-acting NO donor, molsidomine, and the newly synthesized GHRP EP92632 on food intake and GH secretion in rats. Moreover, to verify the specificity of a potential NO involvement, we evaluated whether or not the effects of GHRPs were abolished by a pre-treatment with an inhibitor of NO synthase, N-nitro-arginine-methyl-ester (NAME). Methods: In the food intake experiments, adult Sprague±Dawley male rats underwent acute administration of: (1) EP92632 (160 mg/kg, s.c.); (2) molsidomine (100 mg/kg, i.p.); (3) EP92632+molsidomine; (4) L-NAME (40 and 60 mg/kg, i.p.); (5) EP92632+L-NAME (60 mg/kg, i.p.); (6) EP92632+molsidomine+L-NAME (60 mg/kg, i.p.); and (7) 0.9% saline (0.1 ml/kg, i.p.). After treatments, the cumulative food intake in the 6 post-treatment hours was carefully evaluated. In the neuroendocrine experiments, rats were given the same compounds according to the above reported schedule, except for the use of one dose of NAME (60 mg/kg, i.p.) and a lower EP92632 dose (80 mg/kg, s.c.), and were sampled via atrial cannula. Results: EP92632 significantly stimulated food intake, an effect which was further enhanced by molsidomine, though the latter did not elicit per se any orexigenic effect. L-NAME given alone significantly decreased food intake and abolished the orexigenic effect of the GHRP and the enhancing effect of molsidomine. Plasma GH levels increased significantly following administration of EP92632 but, in contrast to the food intake experiments, molsidomine significantly inhibited both basal and EP92632-stimulated GH secretion; moreover, NAME had a biphasic effect on the EP92632-stimulated GH release: initially inhibitory and then, from 45 min on, stimulatory. NAME did not affect basal GH levels but, surprisingly, combined administration of molsidomine and NAME induced a striking inhibition of both basal and the peptide-stimulated GH release. Conclusions: In summary, these data indicate that NO in the rat is physiologically involved in a stimulatory way in the GHRP-mediated effect on food intake, but exerts a dual action, probably stimulatory at hypothalamic and inhibitory at pituitary levels, on basal and GHRP-stimulated GH secretion. European Journal of Endocrinology 144 155±162

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Section: Discussionmentioning

confidence: 93%

Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

Rigamonti

Cella²,

Cavallera

et al. 2001

European Journal of Endocrinology

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“…Ghrelin is a significant factor in the function and growth of the adenomas over expressing GHS-R [17]. Tsumori et al [18] reported that NO played an inhibitory role in basal GH release and TRH-stimulated hormone release in an autocrine or paracrine fashion through a cGMP-dependent pathway in GH3 cells. However, some studies show that NO enhances the basal and ghrelininduced GH secretion in cultured somatotrophs [19] and cultured human GH-secreting adenomas [20].…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells

Tian

Wang

et al. 2010

Endocr

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Ghrelin stimulates growth hormone release and cell proliferation, which strongly supports a significant role for this peptide in the control of growth hormone-releasing adenomas function and growth. Nitric oxide can influence the stimulatory effects of ghrelin on growth hormone secretion in growth hormone-releasing adenomas. However, the effect of nitric oxide (NO) on ghrelin-induced cell proliferation and the mechanism of this effect in the adenoma were not clarified. In this study, we observed that ghrelin, at a concentration of 10⁻⁹ to 10⁻⁶ M, significantly increased BrdU incorporation into rat GH3 cells. A NO donor, S-nitroso-N-acetylpenicillamine (SNAP), blunted basal, and ghrelin-induced cell proliferation. A blocker of NO synthase, Nw-nitro-L-arginine methyl ester hydrochloride (NAME), had no influence on these actions. The activation of extracellular signal-regulated kinase (ERK) 1/2 was examined by western blotting. The results showed that SNAP reduced ghrelin-stimulated ERK1/2 activation but NAME had no influence on this activation. Together, this study indicates that NO inhibited ghrelin-induced cell proliferation by blocking ERK1/2 activation in GH3 cells.

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“…In the study of Tsumori et al . (17), NO scavenging and cGMP antagonists increased agonist‐induced GH release leading to the conclusion that NO inhibits GH release through a cGMP‐dependent mechanism. By contrast, Pinelle et al .…”

Section: Discussionmentioning

confidence: 99%

“…(16) reported that NO‐stimulated GH secretion from rat hemipituitaries in vitro was unaffected by inhibitors of the GC/cGMP cascade and not mimicked by cGMP, suggesting that NO stimulates GH through a cGMP‐independent mechanism. By contrast, a study with GH 3 cells showed that a NO scavenger increased both basal and stimulated GH release, and that a cGMP antagonist increased stimulated GH secretion (17). This suggests that NO acts through cGMP to inhibit GH secretion.…”

mentioning

confidence: 99%

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

Uretsky

Weiss²,

Yunker

et al. 2003

J Neuroendocrinology

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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.

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Endogenous Nitric Oxide Inhibits Growth Hormone Secretion through Cyclic Guanosine Monophosphate-Dependent Mechanisms in GH3 Cells.

Cited by 15 publications

References 33 publications

Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

Contrasting effects of nitric oxide on food intake and GH secretion stimulated by a GH-releasing peptide

Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells

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

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