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

Abstract

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 Blood was withdrawn continuously between 2200-0600 h at a constant rate of 5 mL/20 min.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...

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

“…There was also a positive correlation between the basal ir-GHRH concentrations and the stage of puberty. This is in agreement with previous findings by our group that the number of nocturnal ir-GHRH pulses and the ir-GHRH amplitude in the peripheral circulation increase in puberty [31]. Argente et al [1] have also shown that pubertal children have higher basal ir-GHRH levels than prepubertal children and suggested that the dramatic rise in plasma GHRH concentrations during puberty indicates a role for this peptide in the adolescent growth spurt.…”

“…Changes in circulating ir-GHRH concentrations have also been claimed to correlate with the secretion of GH [21,24], suggesting that peripheral plasma ir-GHRH measurement reflects hypothalamic function. Our own results also support the view that a considerable proportion of human peripheral ir-GHRH is derived from hypothalamus, since nocturnal ir-GHRH and GH peaks show a close temporal relationship [31].…”

Urinary excretion of GH in healthy individuals and patients with acromegaly, hypopituitarism and dwarfism

“…Some groups have concluded that puberty had no effect on GH secretion (3,4). Some groups have concluded that puberty had no effect on GH secretion (3,4).…”

Physiological and Pathological Growth Hormone Secretion

“…The major secretory burst of GH secretion generally appears within 120 minutes after the JOURNAL 16 , during the first phase of slow wave · > 17 sleep ' , and correction of sleep abnormalities (especially those related to REM sleep) is associated with normalization of GH secretory patterns 18 . Patterns of GH secretion (and that of sleep onset) are themselves under genetic control 3 .…”