Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor. Intermittent secretion or response attenuation.

Webb, Cheryle; Vance, Mary Lee; Thorner, M. O.; Perisutti, Gladys; Thominet, Jennifer L.; Rivier, Jean; Vale, Wylie; Frohman, Lawrence A.

doi:10.1172/jci111424

Cited by 81 publications

(32 citation statements)

References 30 publications

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“…Although the immunoreactive GRF levels did vary, they only accounted for 6% of the variation in GH secretion. In addition, the minimum levels observed (5 ng/ml) were 10-20-fold greater than the minimum levels we have observed that stimulate GH secretion in normal subjects (i.e., 300 pg/ml) (4). We calculated that this tumor secretes -4 mg of GRF per day, and thus this patient was exposed to the equivalent of a continuous infusion of GRF at a dose in excess of 28 ng/kg per min.…”

Section: Discussionmentioning

confidence: 84%

“…During infusions of incremental doses of hGRF-40, 1, 3.3, 10, and 33 ng/kg per min, each for 90 min, there appears to be a dose-related increase of GH secretion during the l-10-ng/kg per min infusions. During the 33-ng/kg per min dose, the effect wanes (4). However, there is great variability in the magnitude and timing of the GH responses among subjects.…”

Section: Introductionmentioning

confidence: 99%

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Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

Vance¹,

Kaiser²,

Evans³

et al. 1985

J. Clin. Invest.

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181

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Growth hormone (GH) secretory patterns were studied in a patient with ectopic growth hormone releasing factor (GRF) secretion and in normal men given continuous infusions of human growth hormone releasing factor (1-40)-OH (hGRF-40). In the patient with ectopic GRF secretion, GH secretion was pulsatile despite continuously elevated immunoreactive GRF levels. To determine if pulsatile GH secretion is maintained in normal subjects, we administered to six healthy young men vehicle or hGRF-40, 2 ng/kg per min, for 24 h and gave a supramaximal intravenous bolus dose of hGRF-40, 3.3 Aig/kg, after 23.5 h of infusion. hGRF-40 infusion resulted in greater GH secretion than did vehicle infusion and pulsatile GH secretion was maintained throughout hGRF40 infusion. During the 23.5 h of vehicle infusion, total GH secretion (microgram; mean±SEM) was 634±151 compared with 1,576±284 during hGRF-40 infusion (P = 0.042). The GH response to the intravenous bolus of hGRF-40 was greater after vehicle infusion than after hGRF-40 infusion; 877±170 and 386±125 ,ug of GH was secreted after the bolus on vehicle and hGRF-40 days, respectively (P = 0.015). The total amount of GH secreted during the 25.5 h of the two study days was not different; 1,504±260 and 1,952±383 1g were secreted during vehicle and hGRF40 days, respectively (P = 0.36). Not only was pulsatile GH secretion maintained during hGRF40 infusion, but there was augmentation of naturally occurring GH pulses, which is in contrast to the effect of gonadotropin-releasing hormone on gonadotropin secretion. We suggest that GH pulses are a result of GRF secretion that is associated with a diminution or withdrawal of somatostatin secretion.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

Vance¹,

Kaiser²,

Evans³

et al. 1985

J. Clin. Invest.

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181

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“…Infusion of GHRH at a constant rate in normal adults produces a persistent effect on GH secretion that is characterized by enhanced pulsatile secretion and an elevation of baseline GH secretion (10,26). These effects can be observed with infusions as short as a few hours and they persist for as long as 2 wk (27).…”

Section: Discussionmentioning

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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“…We did not measure peripheral somatostatin in this study as we were unable to demonstrate a change in somatostatin concentrations (unpublished data) during previous dose-response investigations with GRF-44-NH2. Other investigators have reported no change in somatostatin concentration following intravenous bolus administration of (32) and no change in thyroid-stimulating hormone or thyrotropin-releasing factor-induced thyroid-stimulating hormone levels during continuous intravenous infusion of GRF-40 (33).…”

Section: In Vivomentioning

confidence: 95%

Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.

Rosenthal¹,

Hulse²,

Kaplan³

et al. 1986

J. Clin. Invest.

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Previous studies from this laboratory and by others in rats, monkeys, and humans support the concept that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism. With the availability of human growth hormone-releasing factor (GRF), the possible existence of such a mechanism was reexplored by examining the effect of exogenous GH on the GH response induced by GRF-44-NH2 in six normal men (mean age, 32.4 yr). In all subjects the plasma GH response evoked by GRF-44-NH2 (1 ag/kg i.v. bolus) was studied before and after 5 d of placebo (1 ml normal saline i.m. every 12 h), and then before and 12 h after 5 d of biosynthetic methionyl human GH (5 U i.m. every 12 h). The GH response to GRF (maximal increment over time 0 value) was significantly inhibited after GH treatment (0-13 vs. 23-11.2 ng/ml before treatment, P = 0.05), but was not significantly affected by placebo. This impaired pituitary response to GRF persisted for at least 24 h following exogenous GH treatment in two subjects who underwent further study. Serum somatomedin-C concentrations were significantly increased after 5 d of GH treatment (2.66-5.00 vs. 0.92-1.91 U/ml before treatment, P = <0.01). The impaired pituitary response to GRF may be mediated indirectly through somatomedin, somatostatin, by a direct effect of GH on the pituitary somatotropes, or by all of these mechanisms. These data suggest that after GH treatment, the blunted GH response to synthetic GRF is not solely a consequence of the inhibition of hypothalamic GRF secretion.

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Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor. Intermittent secretion or response attenuation.

Cited by 81 publications

References 30 publications

Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

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

Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.

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