Human Pancreatic Tumor Growth Hormone-Releasing Factor: Dose-Response Relationships in Normal Man*

Vance, Mary Lee; Borges, Joaão L. C.; Kaiser, Donald L.; Evans, William S.; Furlanetto, Richard W.; Thominet, Jennifer L.; Frohman, Lawrence A.; Rogol, Alan D.; MacLeod, Robert M.; Bloom, Stephen R.; Rivier, Jean; Vale, Wylie; Thorner, Michael O.

doi:10.1210/jcem-58-5-838

Cited by 128 publications

(38 citation statements)

References 18 publications

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“…It should be noted that the subjects assigned to experiment 1 and experiment 2 were different. Considerable variabilities in GH responsiveness to GHRH among individual subjects in normal men (25,26) and acromegaly (27) have been reported. Therefore, different GH responses to GHRH seen in this study were considered within the normal range.…”

Section: Resultsmentioning

confidence: 99%

Acute hyperglycemia and activation of the beta-adrenergic system exhibit synergistic inhibitory actions on growth hormone (GH) releasing hormone-induced GH release

Park

Yang²,

Woo³

et al. 2003

European Journal of Endocrinology

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Objective: Acute hyperglycemia stimulates somatostatin (SRIH) release by the hypothalamus which, in turn, suppresses growth hormone (GH) secretion from the anterior pituitary gland. Although it has been suggested that the cholinergic pathway mediates glucose-induced SRIH release, other regulatory systems have not been examined. Therefore, we investigated whether blocking or activating the b-adrenergic pathway alters glucose-mediated inhibition of GH release. Design and methods: One set of experiments was performed with a b-adrenergic antagonist, propranolol, and the other set with a b-adrenergic agonist, isoproterenol. Each set of experiments was performed in ten healthy subjects and consisted of four tests. Test 1, a 100 mg GHRH bolus i.v. at 0 min; test 2, 100 g glucose orally at 2 30 min, followed by a 100 mg GHRH bolus at 0 min; test 3, after a 100 mg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 mg/kg) was administered between 0 and 120 min; test 4, after a 100 g glucose oral load at 230 min, and a 100 mg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 mg/kg) was administered between 0 and 120 min. Blood was drawn every 10 min from 2 30 min to 120 min to measure GH and glucose concentrations. Results: Pretreatment with glucose significantly suppressed GHRH-induced GH secretion. Propranolol infusion significantly increased the GHRH-induced GH secretion, but it did not block glucose-induced suppression of GH secretion. Isoproterenol infusion alone significantly suppressed GHRH-induced GH secretion and augmented the inhibitory action of glucose on GH release. Conclusion: This study demonstrates that glucose-induced suppression of GHRH-stimulated GH release is independent of b-adrenergic tone. Since previous data supports a role for SRIH in both glucose and b-adrenergic suppression of GH release, the current results suggest that subsets of SRIH neurons are differentially responsive to these external cues. Therefore, a combined glucose and isoproterenol test may provide a useful assessment of hypothalamic somatostatinergic activity.

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Section: Resultsmentioning

confidence: 99%

Acute hyperglycemia and activation of the beta-adrenergic system exhibit synergistic inhibitory actions on growth hormone (GH) releasing hormone-induced GH release

Park

Yang²,

Woo³

et al. 2003

European Journal of Endocrinology

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“…GHRH stimulation has therefore been advocated as a physiological test of pituitary somatotroph reserve and as a potential tool for the evaluation of clinical disorders of growth (4)(5)(6). The usefulness of this test, however, has been limited by the marked variability in the amplitude of the responses (1, 7,8). The range of GH responses in normal subjects varies from very brisk to barely detectable, a far greater variability than that observed with administration of any other hypothalamic releasing factor.…”

mentioning

confidence: 99%

lntra‐ and Inter‐Individual Variability in Growth Hormone Responses to Growth Hormone‐Releasing Hormone*

Fornito

Calogero

Mongioí

et al. 1990

J Neuroendocrinology

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Normal subjects show a wide range of growth hormone (GH) responses to growth hormone-releasing hormone (GHRH) stimulation, but it is uncertain whether this variability reflects differences among individuals or whether it would also be observed on repeated tests of the same subject. To clarify this, we tested nine normal men repeatedly with iv bolus doses of 1 pg/kg GHRH(1-44)NH2. Most subjects showed wide variations in their GH responses on repeated testing, and the intra-individual variability was nearly as great as the inter-individual variability in responses, accounting for about two-thirds of the overall variance. A minority of subjects had lower and less variable responses. Ultradian fluctuations in hypothalamic somatostatin secretion may account for this marked intraindividual variability.The iv injection of growth hormone-releasing hormone (GHRH) produces a rapid, dose-dependent rise in plasma GH concentrations (1-3). GHRH stimulation has therefore been advocated as a physiological test of pituitary somatotroph reserve and as a potential tool for the evaluation of clinical disorders of growth (4-6). The usefulness of this test, however, has been limited by the marked variability in the amplitude of the responses (1, 7, 8). The range of GH responses in normal subjects varies from very brisk to barely detectable, a far greater variability than that observed with administration of any other hypothalamic releasing factor. This high inter-individual variation in responses appears to be independent of the dose injected, and has also been reported after iv infusion of GHRH (9). Some of this variability may be attributable to differences in factors such as body weight (lo), but much occurs between individuals who do not appear to differ in any clinically important features (1, 7, 8).Since GH is under the dual control of GHRH and somatostatin (SRIF), it has been suggested that much of this variability may be due to fluctuating levels of endogenous SRIF secretion, which variably blunts the G H response to injected GHRH (11). We postulated that if this were so, the responses to repeated challenges with GHRH in the same subject should also be highly variable, and an assessment of the relative magnitude of intra-and inter-individual variability in responses should offer a guide to the magnitude of this effect. To test this hypothesis, we evaluated the GH responses to bolus doses of GHRH in nine normal men, tested repeatedly at intervals of 3 to 6 days. ResultsThe plasma G H responses to the repeated GHRH tests in the nine subjects are shown in Fig. 1. The injection of GHRH induced a prompt release of GH, which peaked between 15 and 90 min after the injection. The range of responses observed was wide, as found in nearly all studies of GHRH effects, with peak responses varying from 2.5 to 50 pg/L. The inter-and intra-individual variability of peak and integrated GH responses are shown in Figs. 2 and 3. There was a marked intra-individual variability. Analysis of variance showed that the intra-individual varianc...

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“…specifically stimulates G H release in normal men (3)(4)(5) and it has been shown that increases in circulating concentrations of ir-GHRH are followed by GH release in some physiologic situations (6,7). However, only a little is known about the role of GHRH in the generation of the nocturnal rhythm of GH secretion.…”

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confidence: 99%

Nocturnal Release of Immunoreactive Growth Hormone-Releasing Hormone and Growth Hormone in Normal Children

et al. 1989

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ABSTRACT. To evaluate the role of growth hormonereleasing hormone (GHRH) in the physiologic release of growth hormone (GH) we studied the nocturnal secretion of immunoreactive GHRH (ir-GHRH) and its relationship to GH release and various stages of sleep in six prepubertal (three boys) and six pubertal children (two boys) with normal stature. Their ages ranged from 8.1 to 14.9 yr and their bone ages from 6.8 to 14.8 yr. Blood was withdrawn continuously between 2200-0600 h at a constant rate of 5 mL/20 min. The EEG was simultaneously registered. The ir-GHRH and GH data were analyzed by a discrete-pulse detection algorithm (Pulsar). The number of nocturnal ir-GHRH pulses varied from 0-8 (median 7) and the number of GH peaks from 2-6 (median 3). Pubertal children had significantly more ( p < 0.05) ir-GHRH pulses and the pulse amplitude was higher ( p < 0.05) than in the prepubertal children. There were no significant differences in the G H parameters between the two groups. The ir-GHRH peaks were not significantly related to any specific sleep stage. The majority of the GH pulses (71%) were associated with slow wave sleep ( p c: 0.001). Two-thirds (69%) of the GHRH peaks preceded closely or coincided with GH pulses ( p < 0.02). Pubertal subjects had more isolated ir-GHRH peaks than prepubertal children (p < 0.05). We conclude that the nocturnal secretion of ir-GHRH is pulsatile and, assuming that the peripheral plasma concentrations of ir-GHRH reflect its release from the hypothalamus, GHRH appears to play a physiologic role in the regulation of GH secretion. The partial dissociation between ir-GHRH and GH pulses suggests that other factors are also involved in the regulation of episodic GH release and/or that some of the circulating ir-GHRH originates from extrahypothalamic sources. Pubertal children have increased ir-GHRH secretion, the importance of which remains to be defined. specifically stimulates G H release in normal men (3-5) and it has been shown that increases in circulating concentrations of ir-GHRH are followed by GH release in some physiologic situations (6, 7). However, only a little is known about the role of GHRH in the generation of the nocturnal rhythm of GH secretion. Based on observations obtained by intravenous administration of GHRH in the rat it has been suggested that there is a steady-state GHRH and somatostatin release from the hypothalamus and an additional 3-to 4-h rhythmic surge of each peptide (8). This interplay provides for the integration of the ultradian rhythm of GH secretion, as observed in the peripheral circulation. Plotsky and Vale (9) have demonstrated with direct measurements of ir-GHRH and ir-somatostatin in the hypophysialportal circulation that ir-GHRH is secreted in a pulsatile fashion and that ir-GHRH pulses occur only in the presence of diminished somatostatin release. GHRH infusion studies in man also suggest that GH secretion is regulated by dynamic interaction between GHRH and somatostatin (10, 11). Our study was aimed at evaluating nocturnal variation in the circu...

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Human Pancreatic Tumor Growth Hormone-Releasing Factor: Dose-Response Relationships in Normal Man*

Cited by 128 publications

References 18 publications

Acute hyperglycemia and activation of the beta-adrenergic system exhibit synergistic inhibitory actions on growth hormone (GH) releasing hormone-induced GH release

Acute hyperglycemia and activation of the beta-adrenergic system exhibit synergistic inhibitory actions on growth hormone (GH) releasing hormone-induced GH release

lntra‐ and Inter‐Individual Variability in Growth Hormone Responses to Growth Hormone‐Releasing Hormone*

Nocturnal Release of Immunoreactive Growth Hormone-Releasing Hormone and Growth Hormone in Normal Children

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