Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth hormone release are inhibited by central somatostatin action

Fairhall, K. M.; Mynett, Anita; Robinson, I. C. A. F.

doi:10.1677/joe.0.1440555

Cited by 90 publications

(57 citation statements)

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“…Furthermore, somatostatin was found to inhibit GHRP-6-induced secretion of GH in vitro (Cheng et al 1989. Therefore, although the current study and that of Guillaume et al (1994) do not support a decrease in secretion of somatostatin into hypophysial-portal blood, this does not discount the possibility that GHRP-6 blocks the somatostatin inhibition of GHRH neurons in the arcuate nucleus (Fairhall et al 1995). It is possible, as Fairhall et al (1995) suggested, that GHRP-6 blocks somatostatin receptors, which, in turn, enables secretion of GHRH.…”

Section: Discussioncontrasting

confidence: 84%

“…Therefore, although the current study and that of Guillaume et al (1994) do not support a decrease in secretion of somatostatin into hypophysial-portal blood, this does not discount the possibility that GHRP-6 blocks the somatostatin inhibition of GHRH neurons in the arcuate nucleus (Fairhall et al 1995). It is possible, as Fairhall et al (1995) suggested, that GHRP-6 blocks somatostatin receptors, which, in turn, enables secretion of GHRH. Blockade of somatostatin receptors on GHRH neurons, rather than directly stimulating GHRH neurons does not account for increased expression of c-fos in the arcuate nucleus unless GHRP-6 activates neurons other than GHRH, which, in turn, stimulate secretion of GHRH.…”

Section: Discussioncontrasting

confidence: 75%

“…In addition, GHRP-6 increases expression of c-fos, an immediate-early gene, in the arcuate nucleus, where GHRH neurons are located (Merchenthaler et al 1984), suggesting direct action of GHRP-6 on GHRH neurons (Dickson et al 1995). In contrast, Fairhall et al (1995) reported that GHRP-6 inhibited secretion of somatostatin, thereby enhancing GHRH-induced secretion of GH. Furthermore, somatostatin was found to inhibit GHRP-6-induced secretion of GH in vitro (Cheng et al 1989.…”

Section: Discussionmentioning

confidence: 93%

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GH-releasing peptide-6 overcomes refractoriness of somatotropes to GHRH after feeding

McMahon

Chapin

Radcliff

et al. 2001

Journal of Endocrinology

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After a meal, somatotropes are temporarily refractory to growth hormone-releasing hormone (GHRH), the principal hormone that stimulates secretion of growth hormone (GH). Refractoriness is particularly evident when free access to feed is restricted to a 2-h period each day. GH-releasing peptide-6 (GHRP-6), a synthetic peptide, also stimulates secretion of GH from somatotropes. Because GHRH and GHRP-6 act via different receptors, we hypothesized that GHRP-6 would increase GHRH-induced secretion of GH after feeding. Initially, we determined that intravenous injection of GHRP-6 at 1, 3 and 10 µg/kg body weight (BW) stimulated secretion of GH in a dose-dependent manner. Next, we determined that GHRP-6-and GHRH-induced secretion of GH was lower 1 h after feeding (22·5 and 20 ng/ml respectively) than 1 h before feeding (53·5 and 64·5 ng/ml respectively; pooled ...=8·5). However, a combination of GHRP-6 at 3 µg/kg BW and GHRH at 0·2 µg/kg BW synergistically induced an equal and massive release of GH before and after feeding that was fivefold greater than GHRHinduced release of GH after feeding. Furthermore, the combination of GHRP-6 and GHRH synergistically increased release of GH from somatotropes cultured in vitro. However, it was not clear if GHRP-6 acted only on somatotropes or also acted at the hypothalamus. Therefore, we wanted to determine if GHRP-6 stimulated secretion of GHRH or inhibited secretion of somatostatin, or both. GHRP-6 stimulated secretion of GHRH from bovine hypothalamic slices, but did not alter secretion of somatostatin. We conclude that GHRP-6 acts at the hypothalamus to stimulate secretion of GHRH, and at somatotropes to restore and enhance the responsiveness of somatotropes to GHRH.

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Section: Discussioncontrasting

confidence: 84%

Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 93%

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GH-releasing peptide-6 overcomes refractoriness of somatotropes to GHRH after feeding

McMahon

Chapin

Radcliff

et al. 2001

Journal of Endocrinology

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“…This simplified view is justified for the present simulations, although it is known that flooding the hypothalamus with SRIF prior to ghrelin application will abolish the ghrelin effect (Fairhall et al 1995). This latter effect could easily be implemented using a SRIF threshold for the ghrelin-induced GHRH release.…”

Section: Ghrh Oscillationsmentioning

confidence: 98%

Interactions of ghrelin signaling pathways with the GH neuroendocrine axis: a new and experimentally tested model

Wagner¹,

Caplan²,

Tannenbaum³

2009

Journal of Molecular Endocrinology

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Growth hormone (GH) is secreted in a pulsatile fashion from the pituitary gland into the circulation. Release is governed by two hypothalamic neuropeptides, growth hormone-releasing hormone (GHRH) and somatostatin (SRIF), resulting in secretion episodes with a periodicity of 3 . 3 h in the male rat. Ghrelin is an additional recently identified potent GH-secretagogue. However, its in vivo interactions with the GH neuroendocrine axis remain to be elucidated. Moreover, two different sites of ghrelin synthesis are involved, the stomach and the hypothalamus. We used our previously developed core model of GH oscillations and added the sites of ghrelin action at the pituitary and in the hypothalamus. With this extended model, we simulated the effects of central and peripheral ghrelin injections, monitored the GH profile and compared it with existing experimental results. Systemically administered ghrelin elicits a GH pulse independent of SRIF, but only in the presence of GHRH. The peripheral ghrelin signal is mediated to the brain via the vagus nerve, where it augments the release of GHRH and stimulates the secretion of neuropeptide-Y (NPY). By contrast, centrally administered ghrelin initiates a GH pulse by increasing the GHRH level and by antagonizing the SRIF block at the pituitary. In addition, NPY neurons are activated, which trigger a delayed SRIF surge. The major novel features of the present model are a) the role played by NPY, and b) the dissimilar functions of ghrelin in the hypothalamus and at the pituitary. Furthermore, the predictions of the model were experimentally examined and confirmed.

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“…In combination with substances that inhibit or counteract somatostatin, e.g. ARG, pyridostigmine or GHS (25), GHRH becomes the most potent and reproducible stimulus of GH secretion; it explores the maximal secretory capacity of somatotroph cells that, in turn, reflects the appropriately normal function of hypothalamic network controlling GH synthesis and release. Provided that the peak GH response to these tests is referred to appropriate cut-off limits (!20 mg/l in childhood), they are as reliable as classical provocative tests to distinguish between normal and deficient GH secretory capacity.…”

Section: Diagnosis Of Ghd In Childhoodmentioning

confidence: 99%

Retesting the childhood-onset GH-deficient patient

Gasco¹,

Corneli

Beccuti³

et al. 2008

European Journal of Endocrinology

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GH deficiency (GHD) in adults has to be shown by a single provocative test, provided that it is validated. Insulin tolerance test (ITT) has been indicated as the test of choice; now also glucagon test is validated and represents an alternative. The GHRH plus arginine (ARG) test and testing with GHRH plus a GH secretagogue are equally reliable diagnostic tools, and are now considered as 'golden' standards as ITT. Childhood-onset (CO) GHD needs retesting in late adolescence or young adulthood; this is a major clinical challenge and raises questions about the most appropriate method and cut-off value. Appropriate re-evaluation of GH status is represented by simple measurement of IGF1 concentration off rhGH treatment. Clearly, low IGF1 levels are evidence of persistent severe GHD in subjects with genetic GHD or panhypopituitarism. However, normal IGF1 levels never rule out severe GHD and CO-GHD with normal IGF1 levels must undergo a provocative test. The appropriate GH cut-off limit is specific for each provocative test. As shown by the ROC curve analysis, in late adolescents and young adults, the lowest normal GH peak response to ITT is 6.1 mg/l while that to GHRHCARG test is 19.0 mg/l. These cut-off limits, however, are just indicative as being variable as a function of the assay used. No other test is validated for retesting. As GHRHCARG test mostly explores the GH-releasable pool, normal GH response would be verified by a second ITT in order to rule out subtle hypothalamic defect. European Journal of Endocrinology 159 S45-S52

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Central effects of growth hormone-releasing hexapeptide (GHRP-6) on growth hormone release are inhibited by central somatostatin action

Cited by 90 publications

References 0 publications

GH-releasing peptide-6 overcomes refractoriness of somatotropes to GHRH after feeding

GH-releasing peptide-6 overcomes refractoriness of somatotropes to GHRH after feeding

Interactions of ghrelin signaling pathways with the GH neuroendocrine axis: a new and experimentally tested model

Retesting the childhood-onset GH-deficient patient

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