The Effects of Growth Hormone (GH)-Releasing Peptides on GH Secretion in Perifused Pituitary Cells of Adult Male Rats*

Badger, Thomas M.; Millard, William J.; McCormick, Georges F.; Bowers, Cyril Y.; Martin, Joseph B.

doi:10.1210/endo-115-4-1432

Cited by 119 publications

(43 citation statements)

References 8 publications

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“…Furthermore, the inhibitory effect of SRIF on GHRH-induced GH secretion has been reported in in vitro studies in rats [2,24], in chickens [25], and also in vivo in young bulls [26]. The present study is in agreement with the demonstration that GHRP may be a useful probe to use in investigating the GH secretory mechanisms as reported by Badger et al [20], in their study on rat pituitary cells.…”

Section: Discussionsupporting

confidence: 93%

“…This study showed that GHRH (10-' M) was significantly more potent than GHRP (10-~ M) in stimulating bovine GH release in vitro. The potency of the GHRH-stimulated GH releasing effect over GHRP in the present study coincided with reports of previous studies on rat pituitary incubates [8], or in the perfusion of dispersed anterior pituitary cells in male rats [20]. Moreover, the bovine GH releasing effects could be seen at doses as low as 10-11 M GHRH in perfused adenohypophysis as reported by Hashizume and Kanematsu [22], or at doses as low as 10-12 M GHRH from bovine pituitary cells [29].…”

Section: Discussionsupporting

confidence: 92%

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Effect of Growth Hormone (GH)-Releasing Peptide (GHRP) on the Release of GH from Cultured Anterior Pituitary Cells in Cattle.

1994

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Effect of Growth Hormone (GH)-Releasing Peptide (GHRP) on the Release of GH from Cultured Anterior Pituitary Cells in Cattle.

1994

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“…3B). A similar pattern of GH release has been reported with continuous GHRP-6 exposure both in vitro (Blake & Smith 1991) and in vivo (Badger et al 1984, Clark et al 1989. Possible explanations for these observations could be a GHRP-induced depletion of pituitary GH stores, an increase in an endogenous factor that inhibits GH release with prolonged exposure Figure 2 Representative examples of the GH responses noted in individual conscious and freely moving adult male rats infused with saline for 30 ([17) or 174 ([33) h (A), or hexarelin (100 µmg/h) for 6 (B), 30 (C) or 174 (D) h. Blood samples were drawn for the entirety of the 6 h infusions, while samples were taken during only the last 6 h of the 30 h and 174 h infusions.…”

Section: Discussionsupporting

confidence: 80%

“…His--Trp-Ala-Trp--Phe-Lys-NH 2 (GHRP-6) was the first of these small peptides found to specifically release GH in vitro (Bowers et al 1980, Badger et al 1984, Sartor et al 1985a) and in vivo in a variety of species (Sartor et al 1985b, Ilson et al 1989, Walker et al 1990, Malozowski et al 1991, Hartman et al 1992. More recently, our group has reported the bioactivity of a new GHRP, His--2methyl-Trp-Ala--Phe-Lys-NH 2 (hexarelin) which is biologically active when given i.v., s.c. or orally in conscious adult rats (Conley et al 1994(Conley et al , 1995 and which may be a more potent GH secretagogue than GHRP-6 (Conley et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats

Conley

Gaillard²,

Giustina³

et al. 1998

Journal of Endocrinology

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We have previously shown that hexarelin, a novel GHreleasing peptide (GHRP), is able to elicit GH release when administered i.v., s.c. or by mouth and that it is a more potent GH secretagogue than GHRP-6. In the current study, we investigated the effects of hexarelin administered as repeated doses at 2 h intervals or as a continuous 6, 30 or 174 h infusion to conscious male rats.In the first experiment, adult male Sprague-Dawley rats were prepared with dual indwelling jugular catheters. On the day of experimentation, these animals received three 25 µg/kg i.v. boluses of hexarelin at 2 h intervals with blood sampling at 5, 10, 15, 30, 60, 90 and 120 min after each dose. The mean peak GH response and the mean area under the GH response curve (AUC) for the 30 min after each administration were calculated and are reported as the mean ... For both the peak and AUC results there was a significant (P<0·05) difference in the GH response noted between the first (peak 301 37 ng/ml; AUC 5585 700 ng/ml per 30 min) and second (peak 149 47 ng/ml; AUC 3056 908 ng/ml per 30 min) injections of hexarelin, but not between the first and third (peak 214 49 ng/ml; AUC 3862 844 ng/ml per 30 min). In a second series of experiments, adult male Sprague-Dawley rats received continuous infusions (100 µg/h) of hexarelin or saline (1 ml/h) for 6, 30 or 174 h. Blood samples were collected every 20 min for the duration of the 6 h infusion and for the last 6 h of the two longer hexarelin infusions. Plasma GH concentrations peaked within 40 min of the initiation of infusion, but soon returned to basal levels. Mean plasma GH concentrations did not differ between any of the treatment groups, nor did any of the parameters of pulsatile hormone release analyzed. No significant differences in plasma corticosterone concentrations were noted between any of the treatment groups. On the other hand, while neither the 6 h (941 70 ng/ml) nor the 30 h (954 70 ng/ml) hexarelin infusions resulted in a significant increase in the plasma IGF-I concentrations over those noted in the saline controls (935 65 ng/ml), a 174 h hexarelin infusion did elicit a significant increase (1289 42 ng/ml; P<0·05). Thus it appears that, while continuous exposure to hexarelin does not disrupt normal GH cycling, it may (after up to 174 h of exposure) alter other components of the growth axis. In addition, since the character of pulsatile GH release remained unaltered in response to the hexarelin infusion, it appears that this GHRP may not act by suppression of functional somatostatin tone as has been suggested previously.

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“…Further analogue design based on conformational analysis led to a hexapeptide, His-DTrp-Ala-Trp-DPhe-Lys-NH,, termed G H R P which was shown to be a potent and specific G H secretagogue in a number of in vitro and in vivo models (6)(7)(8)(9)(10)(11). The apparent dissimilarity between both the structure and the size of this hexapeptide and the Structure of the endogenous G R F and its smallest active fragments, together with the much higher potency of G R F compared with G H R P in several test systems, has resulted in very few recent studies of the properties of these small G H R P peptides.…”

mentioning

confidence: 99%

The Effects of a Growth Hormone‐Releasing Peptide and Growth Hormone‐Releasing Factor in Conscious and Anaesthetized Rats

Clark¹,

Carlsson²,

Trojnar³

et al. 1989

J Neuroendocrinology

140

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The growth hormone (GH) releasing ability of GH-releasing factor (GRF) and a GH-releasing hexapeptide, GHRP, have been studied in anaesthetized and conscious male and female rats. The GH responses to GHRP in anaesthetized rats were inconsistent, and this peptide was much less potent than GRF. Continuous iv infusions of GRF or GHRP both caused an initial GH release which was not maintained, and further GH release could be elicited by injection of GRF during an infusion of GHRP and vice versa. In contrast, conscious rats were much more sensitive to GHRP. Infusions of GHRP or GRF both caused an initial GH release. With GRF infusions, GH release continued in the normal episodic pattern whereas with GHRP infusion, GH secretion remained elevated over baseline and the normal pulsatile rhythm was disrupted. Plasma GH levels fell after stopping GHRP infusion, without an immediate resumption of normal GH pulsatility. Conscious male rats responded intermittently to injections of GRF given iv every 45 min, but when such serial injections of GRF were given during a continuous iv infusion of GHRP, the GH responses to GRF became regular and more uniform. These results suggest that GHRP prevents the normal cyclic refractoriness to GRF in male rats by disrupting cyclic somatostatin release. The greater potency of GHRP in conscious rats may also depend on the release of endogenous GRF since passive immunization with an anti-GRF serum reduced the plasma GH response to GHRP infusion. Thus in the conscious animal, GHRP may release GH by complex actions at both a hypothalamic and pituitary level.Although the hypothalamic peptide, growth hormone-releasing factor (GRF) was discovered in 1982 (1,2), other substances with the ability to stimulate the release of growth hormone (GH) had previously been described, and of these, a pentapeptide derived from the enkephalin structure was shown to release G H specifically and separately from opiate activity (3-5). Further analogue design based on conformational analysis led to a hexapeptide, His-DTrp-Ala-Trp-DPhe-Lys-NH,, termed G H R P which was shown to be a potent and specific G H secretagogue in a number of in vitro and in vivo models (6-11). The apparent dissimilarity between both the structure and the size of this hexapeptide and the Structure of the endogenous G R F and its smallest active fragments, together with the much higher potency of G R F compared with G H R P in several test systems, has resulted in very few recent studies of the properties of these small G H R P peptides.

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The Effects of Growth Hormone (GH)-Releasing Peptides on GH Secretion in Perifused Pituitary Cells of Adult Male Rats*

Cited by 119 publications

References 8 publications

Effect of Growth Hormone (GH)-Releasing Peptide (GHRP) on the Release of GH from Cultured Anterior Pituitary Cells in Cattle.

Effect of Growth Hormone (GH)-Releasing Peptide (GHRP) on the Release of GH from Cultured Anterior Pituitary Cells in Cattle.

Effects of repeated doses and continuous infusions of the growth hormone-releasing peptide hexarelin in conscious male rats

The Effects of a Growth Hormone‐Releasing Peptide and Growth Hormone‐Releasing Factor in Conscious and Anaesthetized Rats

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