Effects of GHRP-2 and Hexarelin, Two Synthetic GH-Releasing Peptides, on GH, Prolactin, ACTH and Cortisol Levels in Man. Comparison with the Effects of GHRH, TRH and hCRH

Arvat, Emanuela; Vito, Lidia Di; Maccagno, B.; Broglio, Fabio; Boghen, M.; Deghenghi, Romano; Camanni, F.; Ghigo, Ezio

doi:10.1016/s0196-9781(97)00016-8

Cited by 80 publications

(53 citation statements)

References 26 publications

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“…In this study, the action of ghrelin and GHRP-6 appeared to be GH-specific in dogs, i.e., the stimulants did not induce a significant rise in plasma concentrations of ACTH, cortisol, TSH, LH, and PRL in either the young dogs or the old dogs. The absence of a TSH and LH response to GHSs is compatible with the results of previous studies of the hormone-releasing effects of ghrelin in humans and rats (Arvat et al, 1997;Kojima et al, 1999). In contrast, the stimulatory effect of ghrelin and synthetic GHSs on PRL secretion varies with the species studied.…”

Section: Discussionsupporting

confidence: 91%

“…In humans, ghrelin and synthetic GHSs induced a significant release of PRL which is independent of both gender and age and probably results from direct stimulation of somatomammotroph cells (Arvat et al, 1997;Muccioli et al, 2002;Renner et al, 1994;Takaya et al, 2000). In dogs (Hickey et al, 1994) and rats (Kojima et al, 1999), synthetic GHSs do not stimulate PRL release.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, IV administration of ghrelin or synthetic GHSs, such as hexarelin, considerably increased circulating levels of ACTH and cortisol in healthy humans (Arvat et al, 1997;Massoud et al, 1996;Takaya et al, 2000). Kojima et al (1999) reported that IV administered ghrelin specifically stimulated GH release in anaesthetised rats and in isolated rat pituitary cells, but did not affect the release of other adenohypophy- …”

Section: Discussionmentioning

confidence: 99%

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Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Bhatti

Duchateau

Ham

et al. 2006

The Veterinary Journal

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The effects of three growth hormone secretagogues (GHSs), ghrelin, growth hormone-releasing peptide-6 (GHRP-6), and growth hormone-releasing hormone (GHRH), on the release of adenohypophyseal hormones, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinising hormone (LH), prolactin (PRL) and on cortisol were investigated in young and old healthy Beagle dogs.Ghrelin proved to be the most potent GHS in young dogs, whereas in old dogs GHRH administration was associated with the highest plasma GH concentrations. The mean plasma GH response after administration of ghrelin was significantly lower in the old dogs compared with the young dogs. The mean plasma GH concentration after GHRH and GHRP-6 administration was lower in the old dogs compared with the young dogs, but this difference did not reach statistical significance. In both age groups, the GHSs were specific for GH release as they did not cause significant elevations in the plasma concentrations of ACTH, cortisol, TSH, LH, and PRL. It is concluded that in young dogs, ghrelin is a more powerful stimulator of GH release than either GHRH or GHRP-6. Ageing is associated with a decrease in GH-releasing capacity of ghrelin, whereas this decline is considerably lower for GHRH or GHRP-6.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Bhatti

Duchateau

Ham

et al. 2006

The Veterinary Journal

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“…The specificity of GHSs has been addressed in various animals in a number of studies and reviews, (17,(30)(31)(32)36). Especially, the adreno-corticotroph axis and prolactin (PRL) secretion have been addressed.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterisation of a new oral GH secretagogue, NN703

Hansen¹,

Raun²,

Nielsen³

et al. 1999

European Journal of Endocrinology

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NN703 is a novel orally active GH secretagogue (GHS) derived from ipamorelin. NN703 stimulates GH release from rat pituitary cells in a dose-dependent manner with a potency and efficacy similar to that of GHRP-6. The effect is inhibited by known GHS antagonists, but not by a GH-releasing hormone antagonist.Binding of 35S-MK677 to the human type 1A GHS receptor (GHS-R 1A) stably expressed on BHK cells was inhibited by GHRP-6 and MK677 as expected. NN703 was also able to inhibit the binding of 35 S-MK677. However, the observed K i value was lower than expected, as based on the observed potencies regarding GH release from rat pituitary cells. Similarly, the effect of NN703 on the GHS-R 1A-induced inositol phosphate turnover in these cells showed a lower potency, when compared with GHRP-6 and MK677, than that observed in rat pituitary cells.The effect of i.v. administration of NN703 on GH and cortisol release was studied in swine. The potency and efficacy of NN703 on GH release were determined to be 155 Ϯ 23 nmol/kg and 91 Ϯ 7 ng GH/ml plasma respectively. A 50% increase of cortisol, compared with basal levels, was observed for all the tested doses of NN703, but no dose-dependency was shown.The effect of NN703 on GH release after i.v. and oral dosing in beagle dogs was studied. NN703 dosedependently increased the GH release after oral administration. At the highest dose (20 mmol/kg), a 35-fold increase in peak GH concentration was observed (49.5 Ϯ 17.8 ng/ml, mean Ϯ S.E.M.). After a single i.v. dose of 1 mmol/kg the peak GH plasma concentration was elevated to 38.5 Ϯ 19.6 ng/ml (mean Ϯ S.E.M.) approximately 30 min after dosing and returned to basal level after 360 min. The oral bioavailability was 30%. The plasma half-life of NN703 was 4.1 Ϯ 0.4 h.A long-term biological effect of NN703 was demonstrated in a rat study, where the body weight gain was measured during a 14-day once daily oral challenge with 100 mmol/kg. The body weight gain was significantly increased after 14 days as compared with a vehicle-treated group.In summary, we here describe an orally active and GH specific secretagogue, NN703. This compound acts through a similar mechanism as GHRP-6, but has a different receptor pharmacology. NN703 induced GH release in both swine and dogs after i.v. and/or p.o. administration, had a high degree of GH specificity in swine and significantly increased the body weight gain in rats.

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“…Evidências mostram que após a desconexão hipotálamo-hipofisária, o efeito da hexarelina é completamente abolido (97,98) e que ainda essa droga é capaz de estimular a secreção de ACTH in vitro (99,100).…”

Section: Romanholi and Salgadounclassified

Estados de pseudo-Cushing

Romanholi

Salgado

2007

Arq Bras Endocrinol Metab

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Síndromes de pseudo-Cushing são um grupo heterogêneo de doenças, incluindo alcoolismo, anorexia nervosa, obesidade visceral e depressão, que compartilham muitas das características clínicas e bioquímicas da síndrome de Cushing. Os mecanismos responsáveis para a gênese da síndrome de pseudo-Cushing são fracamente compreendidos. Tem sido sugerido que o hipercortisolismo da síndrome de pseudo-Cushing pode ser resultante do aumento da secreção do hormônio liberador de corticotrofina (CRH) hipotalâmico no contexto de um eixo hipotálamo-hipofisário-adrenal que, de outra maneira, está normalmente constituído. A sobreposição substancial entre as características clínicas e laboratoriais entre muitos pacientes com síndrome de Cushing e aqueles com síndrome de pseudo-Cushing pode tornar o diagnóstico diferencial difícil. Distinguir entre síndrome de pseudo-Cushing e síndrome de Cushing verdadeira é crítico para se prevenir o tratamento desnecessário e potencialmente prejudicial de tais pacientes. Esta breve revisão sumariza os principais eventos patofisiológicos das síndromes de pseudo-Cushing e fornece uma estratégia útil para o seu diagnóstico diferencial.

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Effects of GHRP-2 and Hexarelin, Two Synthetic GH-Releasing Peptides, on GH, Prolactin, ACTH and Cortisol Levels in Man. Comparison with the Effects of GHRH, TRH and hCRH

Cited by 80 publications

References 26 publications

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Pharmacological characterisation of a new oral GH secretagogue, NN703

Estados de pseudo-Cushing

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