Significant Increase In Growth Hormone Research Articles

Plasma Growth Hormone and Prolactin Response to FK 33-824, a Synthetic Opioid Agonist, in Broiler Chickens ,

A synthetic opioid agonist, FK 33-824 ([D-Ala2, N-Me-Phe4, Met-(O)5-ol]-enkephalin), was administered intramuscularly at levels of 0, 1, 25, or 625 μ g/kg of body weight to 4-wk-old Arbor Acres × Arbor Acres broiler cockerels. All levels of FK 33-824 caused the birds to be sedated, with the highest dose causing deep sedation over the 240-min test period. A significant time by treatment interaction was seen for plasma growth hormone (GH). At 30 min after treatment, a significant increase in GH occurred, but this transitory increase returned to control levels at 60 min. A secondary GH peak was observed in the 240-min samples from cockerels given the 625 μ g/kg dose. Significant treatment and time effects and a time by treatment interaction were seen in the plasma prolactin (PRL) response to FK 33-824. Prolactin was increased at 30 and 60 min after treatment with 1 μ g/kg, whereas higher doses seemed to suppress PRL concentrations. Over the 240-min experimental period, PRL concentrations tended to increase in all treatments except in the treatment with the lowest FK 33-824 dose, but the largest transitory increase was observed at 240 min in the birds given the 625 μ g/kg dose. These results suggest that FK 33-824 affected GH and PRL secretion in chickens in a manner different from other opioid agonists. This difference was probably due to the ability of FK 33-824 to bind to multiple opiate receptors, with the highest affinity for μ receptors and lesser affinity for δ receptors, whereas other opioids have high affinity for δ receptors. Effects mediated by μ receptors may be stimulatory for GH and PRL secretion in chickens, whereas δ receptors may cause inhibitory responses.

Lack of involvement of the cholinergic mechanism in vasoactive intestinal peptide- and peptide-histidine methionine-induced growth hormone(GH) responses in acromegaly: Comparison with the GH responses to thyrotropin-releasing hormone and GH-releasing hormone

We examined whether the cholinergic mechanism is involved in the paradoxical GH responses to vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in acromegaly. 28 patients with active acromegaly underwent i.v. bolus injections of thyrotropin-releasing hormone (TRH, 500 μg), GH-releasing hormone (GHRH, 100 μg), VIP (100 μg), and PHM (100 μg) with or without a prior atropine treatment (1 mg, i.m., 30 min before). Blood samples were collected before and at intervals up to 120 min after the injection, and plasma GH levels were measured. In response to TRH, GHRH, VIP and PHM, 23 (82%), 24 (86%), 13 (46%) and 7 (25%) patients, respectively, responded with a significant GH increase (> 50% and 6 μg/l above the basal level). The effect of atropine pretreatment was examined in only these responders to the respective peptides. When the GH responses were estimated by the area under the response curve, the atropine pretreatment was able to significantly suppress the GH response to GHRH, but not to TRH, VIP, or PHM. Although the lack of cholinergic involvement in the TRH-induced GH release in acromegaly is confirmatory to previous reports, the same results with the VIP- and PHM-induced GH release are novel. The present study may suggest that in acromegaly the physiological GH response is mediated by the cholinergic mechanism, but the paradoxical ones are not.

Neuroendocrine regulation of growth hormone secretion in sheep. VII. Effects of GABA

The effects of intravenous (i.v.) or intracerebroventricular (i.c.v.) administration of γ aminobutyric acid (GABA) on plasma growth hormone (GH) concentrations have been examined in sheep. Intravenous administration of GABA resulted in a rapid, significant ( P<0.001) increase in plasma GH. Administration of 10 mg of GABA i.c.v. produced a significant ( P<0.001) increase in GH release. By contrast, 100 mg given i.c.v. was inhibitory and resulted in a decrease ( P<0.05) in plasma GH levels. Concurrent administration of somatostatin (0.5 μg/min i.v. over 1 h) did not alter the plasma GH response to 10 mg GABA given i.c.v. These data are consistent with the concept of dual sites of action for GABA in regulating GH release in sheep, but the exact mechanism through which this effect is mediated remains unclear.

Effects of direct and indirect acetylcholine receptor agonists on growth hormone secretion in humans

Cholinergic pathways in the central nervous system positively influence growth hormone (GH) secretion. In fact pyridostigmine, a cholinesterase inhibitor, enhances both basal and GH-releasing hormone (GHRH)-induced GH secretion while, conversely, pirenzepine, an antagonist of muscarinic M 1 receptors, inhibits the GH response to GHRH and to other physiological and pharmacological stimuli. The effect of the cholinergic system on GH secretion probably takes place via inhibition of the release of endogenous somatostatin. In this study in 36 normal adults (26 males and 10 females, age 22–35 years) we compared the effects of three cholinesterase inhibitors (pyridostigmine, 120 mg p.o., n = 19; neostigmine, 10 μg/kg i.v., n = 6; physostigmine, 12.5 μg/kg i.v., n = 6) and bethanechol, a direct muscarinic receptor agonist that is mainly active on muscarinic M 3 receptors (25 μg/kg i.v., n = 5), on both basal and GHRH (1 μg/kg i.v.)-stimulated GH secretion. Pyridostigmine, neostigmine and physostigmine induced a significant GH increase (peak vs. basal levels, mean ± S.E.: 10.4 ± 1.6 vs. 0.6 ± 0.2 μg/l, P = 0.0001; 13.3 ± 1.2 vs. 0.5 ± 1.1 μg/l, P = 0.004; and 14.9 ± 3.1 vs. 2.7 ± 1.1 μg/l, P = 0.025;, respectively). These drugs also induced a similar potentiation of the GH response to GHRH (peak: 48.3 ± 5.6 vs. 16.2 ± 2.2 μg/l, P = 0.0001; 49.2 ± 2.2 vs. 19.9 ± 5.1 μg/l, P = 0.006; and 76.9 ± 12.4 vs. 18.1 ± 5.3 μg/1, P = 0.001, respectively). By contrast, bethanechol neither enhanced basal GH secretion (peak vs. basal level: 3.3 ± 1.2 vs. 2.6 ± 1.2 μg/l) nor potentiated the GH response to GHRH (peak: 16.3 ± 1.3 vs. 15.4 ± 1.6 μg/l). The present findings strongly confirm the stimulatory role of aetylcholine on GH secretion in man, showing that indirect acetylcholine receptor agonists stimulate GH secretion, while the muscarinic M 3 agonist bethanechol does not. The results exclude that cholinergic stimulation of GH secretion is mediated by muscarinic M 3 receptors, in keeping with the hypothesis that muscarinic M 1 receptors play the main role in the neuroregulation of GH secretion.

Effect of tianeptine on the hypothalamic somatotropic axis in the conscious sheep.

The action of serotonin on growth hormone (GH) secretion is controversial because of interspecies differences and lack of specificity of serotoninergic drugs. Serotonin (5-HT) appears to inhibit GH release in the sheep and in man. We have investigated the site of action of tianeptine, a 5-HT uptake enhancer, in sheep since it is possible to collect hypophysial portal blood for the simultaneous determination of growth hormone-releasing hormone (GHRH) and somatostatin in this species under conscious, unstressed conditions. Tianeptine injection (10 mg/kg i.v.) resulted in a significant, immediate and short-lasting (30 min) increase in peripheral GH (+750%; P < 0.01) and hypophysial portal GHRH (+180%; P < 0.01). No change in the secretion of somatostatin was recorded during the same time. These data suggest that serotoninergic inputs are inhibitory to GH secretion. Tianeptine acts centrally to stimulate GH secretion in the sheep and its effect is mediated through changes in GHRH but not somatostatin release into hypophysial portal blood.

Role of growth hormone (GH)-releasing hormone and somatostatin in the mediation of clonidine-induced GH release in sheep.

GH secretion is stimulated by the administration of an alpha 2-adrenergic agonist, clonidine, in several species, including man. This action is probably mediated at the level of the hypothalamus, where the drug may act through inhibition of somatostatin (SRIH) and/or stimulation of GH-releasing hormone (GHRH) release. We have investigated the mode and site of action of clonidine in sheep, because it is possible to collect hypophysial portal blood for the simultaneous determination of GHRH and SRIH in this species under conscious unstressed conditions. Clonidine injection (0.3 mg, iv) resulted in a significant, immediate, and short-lasting (30-min) increase in peripheral GH (14.4 +/- 3.1 vs. 4.8 +/- 1.1 ng/ml; P < 0.01) and portal GHRH (2.7 +/- 0.5 vs. 1.0 +/- 0.2 pg/min; P < 0.01) levels. No change in SRIH secretion was recorded during the same period. Next, we tested the effect of clonidine in sheep actively immunized against GHRH or SRIH. The alpha 2-adrenergic agonist did not affect GH secretion in the anti-GHRH group, whereas immunization against SRIH did not modify the GH response. Finally, we observed that clonidine did not influence GH release from cultured ovine pituitary cells. These data suggest that clonidine acts centrally to stimulate hypophysial GH secretion in the sheep and that this effect is mediated through changes in GHRH, but not SRIH, release into hypophysial portal blood.

Role of growth hormone (GH)-releasing hormone and somatostatin in the mediation of clonidine-induced GH release in sheep

GH secretion is stimulated by the administration of an alpha 2-adrenergic agonist, clonidine, in several species, including man. This action is probably mediated at the level of the hypothalamus, where the drug may act through inhibition of somatostatin (SRIH) and/or stimulation of GH-releasing hormone (GHRH) release. We have investigated the mode and site of action of clonidine in sheep, because it is possible to collect hypophysial portal blood for the simultaneous determination of GHRH and SRIH in this species under conscious unstressed conditions. Clonidine injection (0.3 mg, iv) resulted in a significant, immediate, and short-lasting (30-min) increase in peripheral GH (14.4 +/- 3.1 vs. 4.8 +/- 1.1 ng/ml; P < 0.01) and portal GHRH (2.7 +/- 0.5 vs. 1.0 +/- 0.2 pg/min; P < 0.01) levels. No change in SRIH secretion was recorded during the same period. Next, we tested the effect of clonidine in sheep actively immunized against GHRH or SRIH. The alpha 2-adrenergic agonist did not affect GH secretion in the anti-GHRH group, whereas immunization against SRIH did not modify the GH response. Finally, we observed that clonidine did not influence GH release from cultured ovine pituitary cells. These data suggest that clonidine acts centrally to stimulate hypophysial GH secretion in the sheep and that this effect is mediated through changes in GHRH, but not SRIH, release into hypophysial portal blood.

Hormonal and blood glucose responsiveness as an indicator of specific emotional arousal in type 1 diabetics

The aim of the present study was to examine, whether individual emotional arousal induced by a specific stress interview may effect growth hormone (GH), cortisol, catecholamine and blood glucose levels in diabetes patients. To test the validity of this hypothesis we subjected 18 Type 1 diabetics and 18 healthy controls to a life event interview which produces individual arousal. During this stress interview catecholamines and plasma cortisol levels showed no significant increase, whereas there was a significant increase of GH over time in both groups ( p<0.04), with a trend in diabetics to have a more marked GH response than controls ( p<0.10). Blood glucose levels remained unaffected by the interview. Depressed diabetics showed significantly higher cortisol increases ( p<0.004) than non-depressed diabetics, whereas there was no difference among depressed and non-depressed controls. Depression was not associated with an increase of other hormones or blood glucose levels in both groups. The results of our study confirm specific pathways in which individual emotional arousal and depression may lead to chronic metabolic disturbances as a result of GH and cortisol hypersecretion.

Moderate exercise increases platelet function in type I diabetic patients without severe angiopathy and in good control.

The aim of this study was to investigate whether a 45-min moderate exercise, performed postprandially with a timing that partially prevented the risk of hypoglycemia, was able to modify platelet function in patients affected by insulin-dependent (type I) diabetes mellitus without severe late complications and in a good metabolic control. We submitted 6 male type I diabetic patients (27.2 +/- 3.4 yr; body mass index, 21.4 +/- 0.6 kg/m2; HbA1c, 7.6 +/- 0.9%) on a daily three-insulin injection regimen, without severe late complications of diabetes, to a 45-min moderate exercise (about 50% of maximal oxygen consumption) with a cycle ergometer, beginning 180 min after breakfast and 195 min after a subcutaneous shot of regular insulin. Serial venous blood samples were conducted to measure plasma glucose, free insulin, counterregulatory hormones (glucagon, growth hormone, cortisol, and catecholamines), platelet sensitivity to ADP, platelet activating factor and collagen, and plasma concentrations of the platelet-specific protein beta-thromboglobulin (a marker of the platelet release reaction in vivo). Exercise was accompanied by a decrease of plasma glucose (from 5.9 +/- 1.2 to 4.6 +/- 1 mmol/L, P = 0.067) and free insulin (from 180 +/- 36 to 114 +/- 30 pmol/L, P = 0.003), and by a significant increase of growth hormone (from 5 +/- 1 to 15 +/- 4 micrograms/L, P = 0.045), cortisol (from 240 +/- 30 to 406 +/- 69 nmol/L, P = 0.018), epinephrine (from 1005 +/- 240 to 5143 +/- 1753 pmol/L, P = 0.077), and norepinephrine (from 5.04 +/- 1.08 to 13.48 +/- 2.98 nmol/L, P = 0.009). Platelet sensitivity to the agonists and plasma concentrations of beta-thromboglobulin increased during the exercise period. In particular, ADP ED50 reached during exercise 61 +/- 16% of basal values (P = 0.048), platelet activating factor ED50 reached 73 +/- 11% (P = 0.043), and collagen ED50 reached 68 +/- 9% (P = 0.008). beta-Thromboglobulin rose from 24 +/- 2 to 32 +/- 3 micrograms/L (P = 0.007). Moderate exercise enhances platelet function in type I diabetic patients without severe angiopathy and in a good metabolic control.

Stimulated growth hormone (GH) secretion in children with delays in pubertal development before and after the onset of puberty: relationship with peripheral plasma GH-releasing hormone and somatostatin levels.

A reduced GH secretion has often been shown in prepubertal children with delays in pubertal development. In order to study the mechanism underlying this finding, we evaluated peripheral circulating levels of GH, GHRH, and somatostatin (SRIH) before and after the onset of sexual development in a group of eight late maturing children (six boys, two girls), comparing the results with those obtained in two groups of five prepubertal and four pubertal short children with familial short stature. GH was measured by a two-site immunoradiometric assay. Both GHRH and SRIH were assayed by specific RIAs after an acetone-petrolether extraction from plasma. Our data showed a significant increase (P less than 0.001) in GH, GHRH, and SRIH levels (peak vs. basal values) in response to L-dopa administration in all groups. In pubertal children with delays in pubertal development GH and GHRH peak values (15.8 +/- 2.2 micrograms/L and 120 +/- 18 pg/mL, respectively) were significantly greater (P less than 0.001) than in the same subjects before puberty (8.2 +/- 0.9 micrograms/L and 79 +/- 9 pg/mL, respectively), whereas SRIH peak values did not significantly change (41 +/- 6 vs. 41 +/- 5 pg/mL; P = NS). Furthermore, prepubertal subjects with delays in pubertal development showed GH and GHRH peak values lower (P less than 0.001) than those of prepubertal subjects with FSS (13.3 +/- 1.8 micrograms/L and 120 +/- 13 pg/mL, respectively), whereas no statistical difference was present between the two groups of subjects after pubertal development (18.2 +/- 2.9 micrograms/L and 128 +/- 11 pg/mL, respectively). In conclusion, these findings support the assumption that in late maturing subjects during prepubertal period the decreased GH secretion may be ascribed to a reduced GHRH secretion, reversible with the onset of puberty, without change in circulating SRIH levels.

Effect of triiodothyronine supplementation on thyrotropin-releasing hormone-induced growth hormone secretion in sex-linked dwarf and normal chicks

The effect of a dietary triiodothyronine (T 3) supplement, of either 0.1 or 0.5 μg/g of feed, was studied on the thyrotropin-releasing hormone (TRH)-induced growth hormone (GH) secretion in sex-linked dwarf ( dw) or normal ( Dw) chicks of both sexes. In normal chicks, 0.1 μg/g T 3 decreased plasma GH levels before TRH as well as the GH increase after TRH, and 0.5 μg/g T3 totally suppressed any response to TRH, either at 4 or at 7 weeks of age. Dwarf chicks were more sensitive to TRH than normals when receiving either 0 or 0.1 μg/g T 3; 0.5 μg/g T 3 abolished the difference between genotypes at 4 weeks of age but not so clearly at 7 weeks of age, where dwarf females showed a slight but still significant GH increase after TRH. Interactions between genotype, TRH injection, and T 3 treatments were often significant at 4 weeks of age and even more at 7 weeks of age. Dwarf chicks receiving 0.1 μg/g T 3, expected to have normal plasma T 3 levels, showed a higher GH response after TRH. This suggests that other hormones may be involved in the regulation of this response, particularly IGF-I, which is known to remain at a low level in T 3-treated dwarf chicks.

Intranasal Administration of Neostigmine Potentiates both Intravenous and Intranasal Growth Hormone (GH)-Releasing Hormone-Induced GH Release in Short Children*

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs. 137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.

Impaired Growth Hormone (GH) Response to Pyridostigmine in Type 1 Diabetic Patients with Exaggerated GH-Releasing Hormone-Stimulated GH Secretion*

In the present study we investigated the effects of the acetylcholinesterase inhibitor pyridostigmine (PD), which is hypothesized to decrease hypothalamic somatostatin tone, alone and in association with GH-releasing hormone (GHRH) on GH secretion in 18 type 1 diabetic patients and 12 normal subjects using a randomized double blind placebo-controlled protocol. All subjects received either 120 mg oral PD or placebo 60 min before iv injection of either human GHRH-(1-29) NH2 (100 micrograms) or sterile water (2 mL). In normal subjects both PD alone and GHRH alone caused a significant increase in GH. PD and GHRH acted in a synergistic fashion when combined. In diabetic patients the GH response to GHRH was variable. To segregate the responses, the ratio between the GH increase after GHRH plus PD and after GHRH alone was calculated for each subject. In 10 diabetic patients (group A) the ratio was lower than 2 SD (P less than 0.05) from the mean response of normal subjects. These patients showed an exaggerated GH increase after GHRH and a lower GH increase after PD with respect to normal subjects. Eight diabetic patients (group B) showed a ratio similar to that in normal subjects and similar GH responses to the stimuli. No significant differences were found between groups A and B with respect to age, body mass index, and blood glucose levels. Duration of diabetes was longer and basal GH levels were higher in group A. Hemoglobin-A1c was higher in group A, but of only borderline statistical significance (P = 0.052). Our data demonstrate that in diabetic patients with exaggerated GH responses to GHRH an increase in cholinergic tone does not affect GH secretion. These data suggest that in some type 1 diabetic patients an altered somatostatinergic control of GH secretion may contribute to their abnormal GH response to GHRH.

Can growth hormone increase, after clonidine administration, predict the dose of human menopausal hormone needed for induction of ovulation?

Recent observations claimed that growth hormone (GH) administration increased the sensitivity of the ovary to gonadotropin stimulation. These findings prompted us to assess whether ovarian response to human menopausal gonadotropin (hMG) is correlated to GH reserve. Before hMG administration, 25 patients were tested for GH reserve by administration of clonidine. Of the 25 patients, 8 showed a significant increase in GH (9.2 +/- 4.5 ng/mL) and needed a significantly lower dose of hMG/human chorionic gonadotropin to elicit a good ovarian response than the 17 patients who did not respond to clonidine administration may help to estimate the initial dose range of hMG necessary for induction of ovulation.

BIOCHEMICAL AND HORMONAL CHANGES DURING A 1000 km ULTRAMARATHON

1. To examine individual hormonal responses to extreme physical stress, blood samples were taken from eight highly trained athletes 1 day before and within 15 min of finishing the 1986 1000 km Sydney to Melbourne Ultramarathon foot race. 2. The baseline hormonal state of these highly trained athletes was quite different from normal. Resting serum conjugated catecholamines--epinephrine (E), norepinephrine (NE), dopamine (D), free E and free D--were significantly elevated above the normal mean (P less than 0.01). ACTH levels were significantly elevated above the normal range. Immunoreactive beta-endorphin (IR-beta EP), growth hormone (GH), prolactin (PRL), testosterone, cortisol and cortisol-binding globulin (CBG) were within the normal range. 3. The effect of the race on serum catecholamine levels was to elevate further free and conjugated NE (P less than 0.01). Other catecholamines, free and conjugated, remained significantly elevated above the normal mean (P less than 0.01). Adrenocorticotrophic hormone (ACTH) remained elevated, and IR-beta EP within the normal range, without significant change. A significant increase in GH (P less than 0.05), PRL (P less than 0.01), and cortisol (P less than 0.01) was seen, with no change in CBG. 4. As a model of chronic physical stress, the ultramarathon runner demonstrates a significantly altered baseline hormonal state as reflected in the primary mediators of the stress response, the catecholamines and the hypothalamic-pituitary-adrenal axis. Their response to severe exercise is distinct from that of untrained individuals in whom conjugated catecholamines decrease and ACTH increase. This may represent hormonal adaptation to prolonged stress.

Discordance between growth hormone (GH) responses after GH-releasing hormone and insulin hypoglycemia in myotonic dystrophy.

Plasma GH responses to human GHRH, arginine, L-dopa, and insulin-induced hypoglycemia were determined in seven myotonic dystrophy (MD) patients. An iv bolus injection of GHRH-(1-44)-NH2 (1 microgram/kg BW) only slightly increased plasma GH concentrations in MD patients. The mean peak plasma GH level after GHRH injection [4.2 +/- 0.8 (+/- SE) micrograms/L] was significantly lower than that in 10 age-matched normal subjects (26.7 +/- 4.3 micrograms/L) or that in 6 patients with progressive muscular dystrophy (22.8 +/- 6.6 micrograms/L) whose nutritional status was similar to that of the MD patients. Even with a larger dose of GHRH (3 micrograms/kg BW), the plasma GH rises were minimal in the MD patients (mean peak, 5.9 +/- 1.8 micrograms/L). The plasma GH responses to a 30-min iv infusion of arginine (0.5 g/kg BW) and oral ingestion of L-dopa (0.5 g) were attenuated to a similar extent, whereas insulin-induced hypoglycemia caused a significant increase in plasma GH in all seven MD patients [mean peak, 17.4 +/- 4.1 (+/- SE) microgram/L]. The plasma TSH responses to TRH and plasma insulin-like growth factor I levels were similar in the MD patients and normal subjects. These findings suggest that 1) the impaired GH release after GHRH, arginine, and L-dopa administration in MD patients is not due to somatotroph deficiency, since the GH response to hypoglycemia is well preserved; and 2) insulin-induced hypoglycemia may stimulate GH release at least in part via inhibition of somatostatin release.

Evidence for a role of delta sleep-inducing peptide in slow-wave sleep and sleep-related growth hormone release in the rat.

To examine the role of delta sleep-inducing peptide (DSIP) in sleep-related growth hormone (GH) release, male rats were deprived of sleep for 4 hr by placing them on a slowly rotating wheel. Sleep deprivation by this method caused a significant increase in GH release, as indicated by the increase in plasma GH concentrations (P less than 0.01), and also in the amount of slow-wave sleep (SWS) (P less than 0.001) above initial values after removal of the animals from the rotating wheel. These increases were blocked by microinjection into the third cerebral ventricle of highly specific antiserum to DSIP. In control rats receiving an equal volume of normal rabbit serum, the significant increase in plasma GH as well as SWS remained after removal of the rats from the wheel. The increased release of endogenous DSIP in the sleep-deprived animals may have caused an increase in SWS as well as plasma GH. Since DSIP increases plasma GH after its injection into the third cerebral ventricle and since passive immunization against DSIP blocks the increase in SWS and GH release that follows the 4 hr of sleep deprivation, the results suggest that DSIP can be a physiological stimulus for sleep-related GH release as well as for the induction of SWS.

Growth hormone, noradrenaline, blood pressure and cortisol responses to clonidine in healthy male volunteers: Dose-response relations and reproducibility

The growth hormone (GH) response to clonidine (CLON) has been investigated to date mostly with CLON doses of 2.0 μg/kg or 150 μg intravenously (IV) The present study investigated GH and blood pressure (BP) responses to CLON (2.0 and 1.5 μg/kg IV) (Study I). Twelve healthy male volunteers were tested with the two CLON doses and saline in a cross-randomized design. Plasma GH, noradrenaline (NA) and cortisol concentrations, BP and sedation were determined. CLON (1.5 and 2.0 μg/kg) induced a significant dose-dependent GH increase, but only the 2.0 μg/kg dose differentiated GH responders from nonresponders. In contrast to GH, NA, cortisol, and BP did not differ significantly after either CLON dose. We also studied GH responses to repeated CLON stimulation (Study II). Ten healthy male volunteers were given four CLON tests (2.0 μg/kg) at three-week intervals. The nine volunteers who participated in both studies were investigated over a time course up to 21 months. The subjects could be classified into those who showed consistent GH responses >5 ng/ml, those who showed consistent GH responses <5 ng/ml, and those who showed both degrees of responses.

Idiopathic growth hormone (GH) deficiency, and GH deficiency secondary to hypothalamic germinoma: effect of single and repeated administration of human GH-releasing factor (hGRF) on plasma GH level and endogenous hGRF-like immunoreactivity level in cerebrospinal fluid.

Plasma GH responses to iv administered synthetic human GH-releasing factor-(1-44)-NH2 (hGRF) and the concentration of endogenous hGRF-like immunoreactivity (hGRF-LI) in the cerebrospinal fluid (CSF) were examined in 16 children with GH deficiency (GHD). Ten patients had idiopathic GHD, and six had GHD secondary to germinoma. An iv bolus hGRF (1 microgram/kg BW) injection test was performed the day before and the day after treatment, with a daily 1-h iv infusion of hGRF (2 micrograms/kg BW) for 3 days. Plasma GH increases (greater than 5 ng/ml) after the first iv bolus injection of hGRF occurred in 2 of the 10 idiopathic GHD children and in 4 of the 6 GHD patients with germinoma whereas the first bolus hGRF injection failed to elicit GH release in the remaining 10 patients. The mean +/- SEM peak plasma GH level after the first bolus hGRF dose in the patients with germinoma (8.2 +/- 2.2 ng/ml) was significantly higher than that in the idiopathic GHD patients (2.9 +/- 0.9 ng/ml; P less than 0.05), but significantly lower than that in normal children with short stature (18.5 +/- 2.5 ng/ml; P less than 0.05). In the 2 patients with germinoma and in 5 of the 8 idiopathic GHD children who did not respond to the first hGRF bolus dose, a significant plasma GH response to hGRF occurred during a daily iv infusion of hGRF for 3 consecutive days, whereas the remaining 3 idiopathic GHD children failed to respond to the daily hGRF infusions. The plasma GH response after the second hGRF bolus dose given after treatment with daily hGRF infusions for 3 days was not different from that after the first hGRF bolus in patients with germinoma or that in the idiopathic GHD children. hGRF-LI was not detected (less than 5.8 pg/ml) in the CSF in any of 5 patients with germinoma, whereas it was present in 5 idiopathic GHD patients (mean, 17.5 +/- 0.9 pg/ml), 3 of whom were nonresponders to daily hGRF infusions. From these results, GHD secondary to destruction of hypothalamic GRF neurons might be defined by the following findings: 1) lack of a GH response to the standard provocative tests acting through the hypothalamus; 2) significant increase in plasma GH after a single bolus and/or repetitive iv administration of hGRF; and 3) undetectable or extremely low levels of endogenous hGRF-LI in the CSF. Most of the idiopathic GHD patients responded to the repetitive hGRF infusion, suggesting insufficient secretion of hypothalamic hGRF as the primary defect. However, since hGRF-LI was detectable in the CSF in some of the idiopathic GHD patients, its pathogenesis must be multifactorial.

Effect of somatostatin on growth hormone and prolactin response to dermorphin in man.

The effects of iv somatostatin (somatotrophin release inhibiting factor (SRIF) on growth hormone (GH) and prolactin (Prl) response to dermorphin (D) were tested in 6 healthy men. In all subjects D induced a significant increase in GH and Prl levels, as expected. SRIF completely blocked the GH-releasing activity of D, whereas it only reduced the Prl-releasing activity. The results confirm that D is a potent stimulant for GH and Prl release in man, and furthermore demonstrate that the action of D on GH secretion can be completely overridden by SRIF.