Variable Plasma Growth Hormone (GH)-Releasing Hormone and GH Responses to Clonidine, L-Dopa, and Insulin in Normal Men*

Tapanainen, Päivi; Knip, Mikael; Lautala, Pentti; Leppäluoto, Juhani

doi:10.1210/jcem-67-4-845

Cited by 49 publications

(24 citation statements)

References 13 publications

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“…ir-GHRH has been detected in the peripheral circulation by ourselves and others (6,(28)(29)(30)(31)(32). The source of this circulating ir-GHRH is, however, uncertain.…”

Section: Discussionmentioning

confidence: 89%

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 Blood was withdrawn continuously between 2200-0600 h at a constant rate of 5 mL/20 min.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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“…ir-GHRH has been detected in the peripheral circulation by ourselves and others (6,(28)(29)(30)(31)(32). The source of this circulating ir-GHRH is, however, uncertain.…”

Section: Discussionmentioning

confidence: 89%

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

et al. 1989

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“…Arginine (22,23) and ornithine (24) have been reported to have no effect on systemic GHRH. In contrast, l-dopa is thought to release hypothalamic GHRH, since l-dopa administration increased peripheral GHRH in normal subjects (17,23,25,26) but not in children with hypothalamic GHRH deficiency (17). Clonidine has been reported either to increase (27) or to have no effect (23,26) on systemic GHRH.…”

Section: Discussionmentioning

confidence: 98%

“…In contrast, l-dopa is thought to release hypothalamic GHRH, since l-dopa administration increased peripheral GHRH in normal subjects (17,23,25,26) but not in children with hypothalamic GHRH deficiency (17). Clonidine has been reported either to increase (27) or to have no effect (23,26) on systemic GHRH. Similarly, a rise in peripheral GHRH during hypoglycemia was documented by some (22,28) but not all groups (23,26,27).…”

Section: Discussionmentioning

confidence: 98%

“…Clonidine has been reported either to increase (27) or to have no effect (23,26) on systemic GHRH. Similarly, a rise in peripheral GHRH during hypoglycemia was documented by some (22,28) but not all groups (23,26,27). The several thousand-fold dilution of pituitary-portal GHRH and SRIF in the systemic circulation makes these data difficult to interpret, and, moreover, systemic GHRH (28,29) and SRIF (30) are not necessarily of hypothalamic origin.…”

Section: Discussionmentioning

confidence: 99%

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Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli.

1996

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The roles of hypothalamic growth hormone-releasing hormone (GHRH) and of somatostatin (SRIF) in pharmacologically stimulated growth hormone (GH) secretion in humans are unclear. GH responses could result either from GHRH release or from acute decline in SRIF secretion. To assess directly the role of endogenous GHRH in human GH secretion, we have used a competitive GHRH antagonist, ( N -Ac-Tyr 1 , D -Arg 2 )GHRH(1-29)NH 2 (GHRH-Ant), which we have previously shown is able to block the GH response to GHRH. We first tested whether an acute decline in SRIF, independent of GHRH action, would release GH. Pretreatment with GHRH-Ant abolished the GH response to exogenous GHRH (0.33 g/kg i.v.) but did not modify the GH rise after termination of an SRIF infusion. We then investigated the role of endogenous GHRH in the GH responses to pharmacologic stimuli of GH release. The GH responses to arginine (30 g i.v. over 30 min), L -dopa (0.5 g orally), insulin hypoglycemia (0.1 U/kg i.v.), clonidine (0.25 mg orally), or pyridostigmine (60 mg orally) were measured in healthy young men after pretreatment with either saline or GHRHAnt 400 g/kg i.v. In every case, GH release was significantly suppressed by GHRH-Ant. We conclude that endogenous GHRH is required for the GH response to each of these pharmacologic stimuli. Acute release of hypothalamic GHRH may be a common mechanism by which these compounds mediate GH secretion. ( J. Clin. Invest. 1996. 97: 934-940.)

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“…Classical provocative stimuli of growth hormone (GH) secretion such as insulin-induced hypoglycaemia (ITT), arginine (ARG), clonidine (CLO), glucagon (GLU) and levodopa have been widely used in clinical practice for approximately 30 years (1)(2)(3)(4)(5)(6)(7)(8) and the diagnosis of GH deficiency (GHD) always includes an evaluation of the GH response to provocative testing (9). However, while a normal GH response to provocative testing does not definitively rule out GH insufficiency in childhood, severe GHD in adults must be demonstrated by provocative tests only (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Comparisons among old and new provocative tests of GH secretion in 178 normal adults

Aimaretti

Baffoni

DiVito

et al. 2000

European Journal of Endocrinology

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Classical provocative stimuli of GH secretion such as insulin-induced hypoglycaemia, arginine, clonidine, glucagon and levodopa have been widely used in clinical practice for approximately 30 years. On the other hand, in the last 10 years new potent stimuli of GH secretion have been proposed, but an extensive comparison with the classical ones has rarely been performed, at least in adults.In order to compare the GH-releasing activity of old and new provocative stimuli of GH secretion, and to define the normative values of the GH response, in 178 normal adults (95 males, 83 females; age range: 20-50 years, all within Ϯ15% of their ideal body weight), we studied the GH response to: insulin-induced hypoglycaemia (ITT, 0.1 IU/kg i.v.), arginine (ARG, 0.5 g/kg i.v.), clonidine (CLO, 300 mg/kg p.o.), glucagon (GLU, 1 mg i.m.), pyridostigmine (PD, 120 mg p.o.), galanin (GAL, 80 pmol/kg per min), GH-releasing hormone (GHRH, 1 mg/kg i.v.), GHRH+ARG, GHRH+PD, hexarelin, a GH-releasing protein (HEX, 2 mg/kg i.v.) and GHRH+HEX (0.25 mg/kg i.v.). The mean (ϮS.E.M.) peak GH response to ITT (21.8Ϯ2.8, range: 3.0-84.0 mg/l) was similar to those to ARG (18.0Ϯ1.6, range: 2.9-39.5 mg/l) or GLU (20.5Ϯ2.2, range: 10.6-36.9 mg/l) which, in turn, were higher (P<0.001) than those to CLO (8.2Ϯ1.6, range: 0.3-21.5 mg/l), PD (9.6Ϯ1.1, range: 2.2-33.0 mg/l) and GAL (9.3Ϯ1.1, range: 3.9-18.3 mg/l). The GH response to GHRH (19.1Ϯ1.5, range: 2.7-55.0 mg/l) was similar to those after ITT, ARG or GLU but clearly lower than those after GHRH+ARG (65.9Ϯ5.5, range: 13.8-171.0 mg/l) and GHRH+PD (50.2Ϯ4.6, range: 17.7-134.5 mg/l) which, in turn, were similar. The GH response to HEX (55.3Ϯ5.5, range: 13.9-163.5 mg/l) was similar to those after GHRH+ARG and GHRH+PD but lower (P<0.001) than that after GHRH+HEX (86.0Ϯ4.3, range: 49.0-125.0 mg/l) which was the most potent stimulus of GH secretion. In this adult population the third centile limits of peak GH response to various stimuli were the following: ITT: 5.3; ARG: 2.9; CLO: 1.5; GLU: 7.6; PD: 2.2; GAL: 4.0; GHRH: 5.0; GHRH+ARG: 17.8; GHRH+PD: 17.9; HEX: 21.6; GHRH+HEX: 57.1.These results confirm that, among classical provocative tests of GH secretion, ITT followed by ARG and GLU are the most potent ones and possess clear limits of normality. GHRH+ARG or PD and HEX are strong stimuli of GH secretion which, however, is maximally stimulated by a combination of GHRH and a low dose of HEX. It is recommended that each test is used with appropriate cut-off limits.

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Variable Plasma Growth Hormone (GH)-Releasing Hormone and GH Responses to Clonidine, L-Dopa, and Insulin in Normal Men*

Cited by 49 publications

References 13 publications

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

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

Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli.

Comparisons among old and new provocative tests of GH secretion in 178 normal adults

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