Interrelationship between the Novel Peptide Ghrelin and Somatostatin/Growth Hormone-Releasing Hormone in Regulation of Pulsatile Growth Hormone Secretion

Tannenbaum, Gloria Shaffer; Epelbaum, Jacques; Bowers, Cyril Y.

doi:10.1210/en.2002-220852

Cited by 218 publications

(152 citation statements)

References 49 publications

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“…1A). Previous studies have demonstrated that while there is direct pituitary interaction, the bulk of the GH-releasing action of ghrelin is mediated via the hypothalamus through stimulation of GH releasing hormone (GHRH) secretion and suppression of somatostatin (8). To examine the specificity of BIM-28163 inhibition of ghrelinstimulated GH secretion, the experiment was repeated substituting GHRH in place of h-ghrelin.…”

Section: In Vivo Effect On Gh Secretionmentioning

confidence: 99%

Novel analogs of ghrelin: physiological and clinical implications

Halem¹,

Taylor²,

Dong³

et al. 2004

European Journal of Endocrinology

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Ghrelin, the 28 amino acid peptide recently identified as the natural ligand for the growth hormone (GH) secretagogue (GHS) receptor, has multiple activities in addition to stimulation of GH secretion, including stimulation of feeding and weight gain. To utilize these actions for potential therapeutic benefit, we have produced analogs of human ghrelin with enhanced metabolic stability, affinity for the GHS receptor, and efficacy in stimulating weight gain. We have also discovered an analog of ghrelin, BIM-28163, that is an antagonist at the GHS receptor and that fully inhibits GHS receptor activation induced by native ghrelin. In vivo, BIM-28163 does not increase GH secretion but fully blocks ghrelin-induced GH secretion. In contrast, BIM-28163 acts as a full agonist with regard to the ghrelin actions of stimulating weight gain and food intake. These results suggest that a receptor other than the GHS receptor mediates the actions of ghrelin on feeding and weight gain. This concept is strengthened by our observation that at certain hypothalamic sites, BIM-28163 acts as an antagonist of ghrelin-induced neuronal activation, while at other sites, both ghrelin and BIM-28163 induce neuronal activation via the same receptor. Collectively, these results indicate the existence of a novel ghrelin receptor that may regulate the feeding activity of ghrelin. Using BIM-28163 as a tool to define the endogenous role of ghrelin in normal GH secretion, we have demonstrated that antagonism of the GHS receptor in normal rats does not impair the pulsatility of GH secretion but lowers the pulse amplitude and mean GH level. These results demonstrate that endogenous ghrelin acts to amplify the basic pattern of GH secretion established by the interplay of hypothalamic GH-releasing hormone and somatostatin. These studies demonstrate the feasibility of creating ghrelin analogs that are selective for specific activities, as well as their utility in dissecting the role of ghrelin in both normal physiology and specific pathologies.European Journal of Endocrinology 151 S71-S75

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Section: In Vivo Effect On Gh Secretionmentioning

confidence: 99%

Novel analogs of ghrelin: physiological and clinical implications

Halem¹,

Taylor²,

Dong³

et al. 2004

European Journal of Endocrinology

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“…Growth hormone (GH) secretion is regulated by two major hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin 14 (SS14) (Tannenbaum et al 2003, Gahete et al 2009). In teleosts, however, a unique component of the multifactorial control of somatotropes is gonadotropin-releasing hormone (GnRH), which directly stimulates GH secretion and mRNA expression chicken (c) GnRHII (or GnRH2) and salmon (s) GnRH (or GnRH3) (Yu et al 1988).…”

Section: Introductionmentioning

confidence: 99%

Seasonal effects of GnIH on basal and GnRH-induced goldfish somatotrope functions

Moussavi¹,

Wlasichuk²,

Chang³

et al. 2014

Journal of Endocrinology

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To understand how gonadotropin-inhibitory hormone (GnIH) regulates goldfish GH cell functions, we monitored GH release and expression during early, mid-, and/or late gonadal recrudescence. In vivo and in vitro responses to goldfish (g) GnIH were different, indicating direct action at the level of pituitary, as well as interactions with other neuroendocrine factors involved in GH regulation. Injection of gGnIH consistently reduced basal serum GH levels but elevated pituitary gh mRNA levels, indicating potential dissociation of GH release and synthesis. Goldfish GnRH (sGnRH and cGnRHII) injection differentially stimulated serum GH and pituitary gh mRNA levels with some seasonal differences; these responses were reduced by gGnIH. In contrast, in vitro application of gGnIH during 24-h static incubation of goldfish pituitary cells generally elevated basal GH release and attenuated sGnRH-induced changes in gh mRNA, while suppressing basal gh mRNA levels at mid-and late recrudescence but elevating them at early recrudescence. gGnIH attenuated the GH release responses to sGnRH during static incubation at early, but not at mid-and late recrudescence. In cell column perifusion experiments examining short-term GH release, gGnIH reduced the cGnRHII-and sGnRH-stimulated secretion at late recrudescence but inhibited tha action of cGnRHII only during mid-recrudescence. Interestingly, a reduction of basal GH release upon perifusion with gGnIH during late recrudescence was followed by a rebound increase in GH release upon gGnIH removal. These results indicate that gGnIH exerts complex effects on basal and GnRH-stimulated goldfish GH cell functions and can differentially affect GH release and mRNA expression in a seasonal reproductive manner.

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“…To the degree that L-arginine antagonizes hypothalamic somatostatin release, we infer that the negative relationship between combined L-arginine/ GHRH-stimulated GH secretion and AVF is not attributable solely to heightened somatostatin outflow. Plausible mechanisms would include impaired stimulation by GHRH acting alone or in synergy with endogenous ghrelin, given the strong facilitative interaction between these two peptides (50).…”

Section: Discussionmentioning

confidence: 99%

Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy

Veldhuis¹,

Keenan²,

Mielke³

et al. 2005

eur j endocrinol

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Objective: Testosterone supplementation increases GH and IGF-I concentrations in healthy older men via unknown mechanisms. We examine the hypotheses that (i) testosterone amplifies stimulation of GH secretion by GH-releasing peptide (GHRP)-2 or GH-releasing hormone (GHRH) infused with L-arginine to limit somatostatin outflow (i.e. upregulates each agonistic pathway), (ii) testosterone augments the effect of both peptidyl secretagogues infused together (i.e. reduces opposition by hypothalamic somatostatin) and (iii) abdominal visceral fat (AVF) mass is a negative determinant of specific secretagogue-stimulated GH secretion. Design: Randomized double-blind crossover design of placebo versus testosterone administration in healthy older men. Methods: Deconvolution analysis was used to estimate basal GH secretion and the mass (integral) and waveform (time-shape) of GH secretory bursts. Results: Statistical contrasts revealed that administration of testosterone compared with placebo in seven men aged 60-77 years increased fasting concentrations of GH (P , 0.01) and IGF-I (P ¼ 0.003), and basal (P , 0.005) and pulsatile (P , 0.01) GH secretion. Testosterone did not alter the absolute value or rank order of secretagogue efficacy: L-arginine/GHRP-2 (23-fold effect over saline) ¼ GHRH/GHRP-2 (20-fold) . L-arginine/GHRH (7.5-fold). Waveform reconstruction indicated that each stimulus pair accelerated initial GH secretion within a burst (P , 0.01). Regression analysis disclosed a significant inverse association between GH secretory-burst mass and computer tomography-estimated AVF following stimulation with L-arginine/GHRH after testosterone supplementation (R 2 ¼ 0.54, P ¼ 0.015). Conclusion: Supraphysiological testosterone concentrations augment GH and IGF-I production in the elderly male without altering maximal somatotrope responses to single and combined GHRH and GHRP-2 drive, thus predicting multifactorial mechanisms of testosterone upregulation.

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Interrelationship between the Novel Peptide Ghrelin and Somatostatin/Growth Hormone-Releasing Hormone in Regulation of Pulsatile Growth Hormone Secretion

Cited by 218 publications

References 49 publications

Novel analogs of ghrelin: physiological and clinical implications

Novel analogs of ghrelin: physiological and clinical implications

Seasonal effects of GnIH on basal and GnRH-induced goldfish somatotrope functions

Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy

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