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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conflicting data are found in the literature concerning the growth hormone response to growth hormone-releasing hormone and the insulin-like growth factor I level in Type I diabetes mellitus. The GH response to GHRH and the serum IGF-I level were studied in 29 moderately to well regulated male diabetic patients and 20 age-matched controls. The mean fasting glucose and HbA1c (normal less than 6.5%) levels were, respectively: 10.2 +/- 0.8 mmol/l and 7.1 +/- 0.2%, and 4.1 +/- 0.1 mmol/l and 5.4 +/- 0.1% (mean +/- SEM). The GH response to GHRH was higher in the diabetic patients at 15, 30 and 45 min (p less than 0.05), and also delta peak GH was higher compared with controls: 34.8 +/- 5.6 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). The serum IGF-I level was lower in the diabetic patients: 460 +/- 30 vs 700 +/- 60 U/l (p less than 0.01). No correlations could be demonstrated between delta peak GH, serum IGF-I or HbA1c level. When only patients with a mean fasting glucose less than or equal to 7.0 mmol/l and normal HbA1c (5.8 +/- 0.3%) were analysed, delta peak GH was also elevated compared with controls: 47.0 +/- 16.3 vs 18.0 +/- 2.4 micrograms/l (p less than 0.02). No difference was observed in GH response or serum IGF-I level in 5 patients with (pre)proliferative retinopathy compared with patients without this complication. It is concluded that in Type I diabetes the GH response to GHRH is increased, even in well regulated patients, and that the serum IGF-I level is depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone in type I diabetic and healthy man. 211 Apr 12

A late rise in serum GH occurs 3-5 h following oral glucose in man. In order to investigate the mechanisms through which this occurs we have studied the late GH rise after oral glucose during administration of a supramaximal dose of GHRH. In eight normal subjects, oral glucose (100 g) greatly enhanced the GH responses to a supramaximal dose of GHRH (50 micrograms bolus, followed immediately by 100 micrograms/h infusion for 3 h) given 3.5 h after the glucose. GH peak (mean +/- SEM) elicited by GHRH (bolus + infusion) rose from 55.2 +/- 20.4 to 133.4 +/- 29.6 mU/l (P less than 0.02) after glucose pretreatment. In conclusion, it is likely that the late rise in GH secretion induced by oral glucose occurs via a non-GHRH-dependent mechanism. These data are consistent with the hypothesis that the delayed GH response to glucose is a consequence of reduced release of somatostatin from the hypothalamus.
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PMID:Effect of oral glucose on the late growth hormone rise and growth hormone responses to GHRH in normal subjects. 211 40

Growth hormone-releasing hormone, GHRH(1-44), was administered intranasally to 16 healthy young adult male volunteers in a placebo-controlled study using a dose of 1,000 micrograms dissolved in two different solvent vehicles: water alone and water with the surface tension-lowering agent Tween 80 (0.12%). The growth hormone (GH)-releasing effects of intranasal GHRH as well as that of the vehicle were established and compared to the effects of 80 micrograms intravenous GHRH. Plasma GH response was assessed by frequent blood sampling over an 180-min period, using both peak response and area under the curve (AUC). The results show that the GH-release effects of intranasal GHRH are comparable whichever vehicle is used, and are similar, with the dose of 1,000 micrograms, to the response obtained following the administration of 80 micrograms intravenous GHRH. Peak GH responses to GHRH (means +/- SEM) were 25.6 +/- 4.2 ng/ml (1,000 micrograms GHRH with water), 32.9 +/- 9.1 ng/ml (1,000 micrograms with water plus Tween 80) and 36.3 +/- 7.8 ng/ml (80 micrograms i.v. administration) (not significant). There was no significant GH response to placebo. Mean peak GH responses occurred after approximately 30 min in all three active treatments (29.2 +/- 2.7, 33.9 +/- 3.2 and 30.9 +/- 3.9 min, respectively). The AUC values (ng.min.ml-1) were not statistically different: 1,914.4 +/- 386.7 (water), 2,176.2 +/- 599.9 (water plus Tween 80) and 2,419.2 +/- 506.9 (i.v.) (not significant). Intranasal GHRH administration was well tolerated in all subjects. Occasional local reactions consisted of a prickly sensation in the nostrils or sneezing irrespective of the vehicle used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A placebo-controlled trial of intranasal growth hormone-releasing hormone [GHRH(1-44)-NH2] administration in normal young adults. 211 56

Use of reverse hemolytic plaque assays revealed that, as in the rat, bovine somatotropes are functionally heterogeneous with respect to regulated GH release. Uniquely, this heterogeneity is manifested by the appearance of a distinct subpopulation of GH cells that release hormone only in the presence of the hypothalamic secretagogues GRF and/or TRH. Although these cells did not release GH in the absence of stimulatory agents, immunocytochemical detection of GH demonstrated these cells were capable of hormone storage. The relative abundance of silent somatotropes varied according to the hypothalamic secretagogue applied to the culture (GRF and/or TRH) and the physiologic state of the tissue donor. In cell cultures obtained from castrated males, 4.2 +/- 1.2%, 3.0 +/- 0.7%, and 6.8 +/- 1.2% (mean +/- SEM; n = 14) of all pituitary cells were induced to release detectable amounts of GH by GRF, TRH, and GRF/TRH, respectively. When pituitary cells obtained from gonad-intact males (n = 4) and females (n = 4) were tested, only incubation with GRF (14.1 +/- 2.5%; 6.9 +/- 2.3%, respectively) and GRF/TRH (15.2 +/- 2.4%; 9.2 +/- 2.6%, respectively) stimulated a significant population of these silent cells. A combined analysis of the proportion of GH secretors and the relative amount of hormone released per cell revealed that a substantial fraction of the GH secreted in vitro after stimulation is attributable to the recruitment of silent somatotropes into the secretory pool. Taken together, these results reveal the existence of a unique form of GH cell heterogeneity--the silent somatotrope. Moreover, our findings demonstrate that this somatotrope population could provide a cellular basis for the readily releasable pool of GH in the bovine pituitary.
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PMID:Bovine pituitary cells exhibit a unique form of somatotrope secretory heterogeneity. 212 61

The GHRH test has been proposed to replace conventional stimuli in the diagnosis of GH deficiency. However the reliability of GHRH in discriminating between normal and GH-deficient children is still uncertain. The aim of this study was to compare the GH-releasing effect of GHRH (1 microgram/kg i.v.) with that of two neuroactive drugs, clonidine (CLON, 150 micrograms/m2 orally), an alpha 2-receptor agonist, and pyridostigmine (PD, 60 mg orally), a cholinergic agonist that inhibits cholinesterases, in 23 children and adolescents with normal and familial short stature. The plasma GH peak (mean +/- SEM) after GHRH (20.3 +/- 2.5 ng/ml), CLON (17.0 +/- 2.1 ng/ml) and PD (14.9 +/- 1.5 ng/ml) did not significantly differ. According to the conventional limit (less than 10 ng/ml), a false negative response was present in 6, 5 and 6 subjects after GHRH, CLON and PD, respectively. In conclusion, GHRH, CLON and PD have a similar GH-releasing effect. A similar percentage of false negative responses was observed with all tests and this evidence reduces their diagnostic ability.
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PMID:Comparison of growth hormone-releasing effect of growth hormone-releasing hormone, clonidine and pyridostigmine in normal children and adolescents. GH-releasing effect of GHRH, clonidine and pyridostigmine. 226 95

It has been shown that alpha 2-adrenoreceptor activation induced by clonidine (CLON) increases plasma GH levels in both adults and children. In this study the effects of CLON (150 micrograms/m2, orally) on GH secretion were studied both in the morning (from 0800-1100 h) and at night (from 2300-0200 h) in nine short children previously shown to have normal spontaneous nocturnal GH secretion. In the morning, CLON induced a GH increase higher than placebo [peak (mean +/- SEM), 23.8 +/- 4.3 vs. 3.4 +/- 1.4 micrograms/L; P = 0.0001; area under curve (AUC), 624.4 +/- 62.7 vs. 135.6 +/- 33.3 micrograms/L.h; P less than 0.00001]. In the night, no difference was observed between GH secretion after CLON (peak, 15.4 +/- 3.2 micrograms/L; AUC, 562.2 +/- 57.5 micrograms/L.h) and placebo (peak, 13.1 +/- 4.7 micrograms/L; AUC, 497.2 +/- 83.5 micrograms/L.h). Spontaneous GH secretion was higher during the night than in the morning (P = 0.0001), whereas nocturnal GH secretion overlapped with that in the morning after CLON. The data presented show that alpha 2-adrenoreceptor activation is probably mediated by increased endogenous GHRH release; our results suggest that the endogenous GHRH secretion is maximally stimulated at night.
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PMID:Acute clonidine administration potentiates spontaneous diurnal, but not nocturnal, growth hormone secretion in normal short children. 238 Mar 38

In an attempt to clarify the regulatory role in GH secretion of central alpha-adrenergic and dopaminergic mechanisms, the effects of iv administration of alpha 1- and alpha 2-adrenergic antagonists and dopaminergic antagonists were investigated in undisturbed conscious male rabbits. During a 6-h observation period (1030-1630 h), control animals demonstrated spontaneous pulsatile GH secretion with mean (+/- SEM) 6-h GH levels of 6.49 +/- 0.54 ng/ml (n = 16). Intravenous injection of yohimbine (YOM; an alpha 2-antagonist), chlorpromazine (CPZ), and haloperidol (HAL; dopamine and alpha-adrenergic antagonists) completely suppressed this pulsatile GH secretion (mean 6-h GH levels, 2.98 +/- 0.24, 3.48 +/- 0.24, and 2.91 +/- 0.29 ng/ml, respectively; P less than 0.001), whereas prazosin (an alpha 1-antagonist), pimozide (a selective dopamine antagonist), sulpiride, and YM-09151-2 (YM; D2-specific antagonists) failed to affect the GH secretory pattern (mean 6-h GH levels, 6.61 +/- 0.73, 6.71 +/- 0.56, 5.44 +/- 0.44, and 6.87 +/- 1.44 ng/ml, respectively). While an iv injection of 2 micrograms synthetic human GH-releasing factor-(1-44)-NH2 (hGRF) induced GH rises in prazosin-, HAL-, pimozide-, sulpiride-, and YM-treated rabbits as well as control rabbits, YOM and CPZ completely abolished these GH responses to hGRF injection. An iv injection of 10 ml antisomatostatin gamma-globulin caused a prompt and transient GH rise, followed by a sustained elevation of GH trough levels in normal control rabbits. YOM treatment completely abolished this highly oscillated GH release. However, suppression by YOM or CPZ of hGRF-induced GH rises was significantly reversed by iv administration of 10 ml antisomatostatin gamma-globulin. Therefore, the inhibitory effect of YOM and CPZ on both episodic GH release and hGRF-induced GH rises is due to the enhanced release of somatostatin, with a simultaneous suppression of endogenous GRF. On the other hand, HAL, possessing a weaker alpha-blocking action than CPZ, blunted pulsatile GH secretion, but only modestly suppressed hGRF-induced GH rises. These results suggest the following. 1) Central alpha 2-adrenergic mechanisms play a more important role in the regulation of GH secretion than alpha 1-adrenergic mechanisms in the rabbit as well as in other species. 2) The alpha 2-adrenergic blockade causes suppression of the release of hypothalamic GRF and enhanced release of endogenous somatostatin, thereby suppressing GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alpha 2-adrenergic control of growth hormone (GH) secretion in conscious male rabbits: involvement of endogenous GH-releasing factor and somatostatin. 247 28

We previously reported that systemic administration of the recently described GRF peptide antagonist (N-Ac-Tyr1,D-Arg2)GRF-(1-29)-NH2 to adult male rats would suppress the pulsatile release of GH. In the present study, we have sought to determine whether this same antagonist would be efficacious in immature male rats to block spontaneous GH secretion and, as a result, retard several parameters of somatic growth. Indwelling Silastic catheters were placed into the jugular veins of immature male rats (120-140 g) at 29 days of age. After a recovery period of 48 h, beginning at 1000 h, 100-400 micrograms/kg GRF antagonist or its vehicle (controls) were injected iv immediately after withdrawing an initial blood sample from conscious undisturbed animals. Subsequent samples were obtained every 20 min until 1520 h. Red blood cells were resuspended in a restorative volume of saline and reinjected after each blood sample. Results showed that both doses of antagonist prevented the two major periods of episodic GH release observed in controls. For example, mean plasma GH (+/- SEM; nanograms per ml) at 1120 h was 9.0 +/- 2.7 in antagonist-treated rats and 37.1 +/- 5.1 in controls (P less than 0.05). Mean plasma GH (+/- SEM) at 1340 h was 10.8 +/- 3.7 in antagonist-treated rats and 38.8 +/- 9.6 in controls (P less than 0.05). Injection of 400 micrograms/kg of the structurally related VIP antagonist (N-Ac-Tyr1,D-Phe2)GRF-(1-29)-NH2, iv failed to suppress spontaneous GH release. GRF antagonist (100 micrograms/kg) was next administered twice daily iv for 4 days to 31-day-old rats in metabolic cages. This treatment essentially arrested the normal rapid body weight gain, significantly suppressed increases in body and tail lengths, and reduced increases in heart and kidney weights (P less than 0.01). Food intake and fecal output were unchanged by antagonist treatment and, therefore, did not contribute to the observed effects. These results support the idea that a number of tissues and organs are stimulated by the pulsatile secretion of GH and that a peptidic GRF receptor antagonist is useful in blocking episodic GH release in immature animals. As a consequence, this specific antagonist is effective in suppressing numerous aspects of somatic growth.
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PMID:Inhibition of pulsatile growth hormone (GH) secretion and somatic growth in immature rats with a synthetic GH-releasing factor antagonist. 249 21

It has been shown that enhanced cholinergic tone induced by pyridostigmine (PD) increases both basal and GHRH-stimulated GH levels in both adults and children. In this study the effects of PD (60 mg orally) on GH secretion were studied both in the morning (from 8.00 to 12.00) and in the night (from 23.00 to 3.00) in 7 short children previously shown as having a normal spontaneous nocturnal GH secretion. In the morning, PD induced a GH increase higher than saline (peak, mean +/- SEM: 17.4 +/- 3.4 vs. 5.5 +/- 3.0 ng/ml, p less than 0.02; area under curve (AUC): 360.8 +/- 71.4 vs. 109.4 +/- 44.7 ng/ml/h, p less than 0.01). In the night, no difference was observed between GH secretion after PD (peak: 16.7 +/- 2.4 ng/ml; AUC: 468.2 +/- 95.5 ng/ml/h) and saline (peak: 16.0 +/- 2.7 ng/ml; AUC: 409.1 +/- 97.7 ng/ml/h). Spontaneous GH secretion was higher during the night than in the morning (p less than 0.02) whereas nocturnal GH secretion overlapped with that in the morning after PD. The ability of PD to increase GH secretion during the morning but not GH hypersecretion occurring at night implies that the cholinergic tone in the central nervous system areas controlling GH secretion is already maximally stimulated at night. Since, reportedly, the cholinergic system negatively modulates somatostatin secretion, presence of a physiologically reduced somatostatinergic tone may be envisaged at night.
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PMID:Cholinergic enhancement of pyridostigmine potentiates spontaneous diurnal but not nocturnal growth hormone secretion in short children. 249 54

In normal adults, repeated GHRH administration leads to progressively decreasing somatotrope responses. To verify whether this GH secretory pattern also connotes normal growing children, we have studied the effects of two consecutive (every 120 min) 1 microgram/kg iv GHRH boluses on GH release in normal adults (N = 7, age 23.2-30.6 years) children (N = 6, age 10.4-13.2 years). In the adults, the GH response to the second GHRH bolus (peak, mean +/- SEM; 2.9 +/- 0.8 micrograms/l) was lower (P less than 0.02) than that to the first bolus (15.9 +/- 2.4 micrograms/l). Conversely, in children the GH response to the second GHRH bolus (25.6 +/- 6.3 micrograms/l) overrode the first one (13.6 +/- 6.5 micrograms/l), but this difference did not attain statistical significance. In adults cholinergic enhancement by pyridostigmine, a cholinesterase inhibitor, was previously shown to re-instate, even to potentiate somatotrope responsiveness to consecutive GHRH boluses. Thus, in 5 children GH response to repeated GHRH boluses was retested administering pyridostigmine (60 mg orally) 30 min before the second GHRH bolus. In these subjects, pyridostigmine failed significantly to potentiate the GH responsiveness to the second GHRH bolus (30.3 +/- 4.6 vs 25.0 +/- 7.6 micrograms/l). These data indicate that differently from in adults, in children repeated GHRH administration does not reduce somatotrope responsiveness and that cholinergic enhancement fails to potentiate GH responsiveness to the second GHRH bolus.
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PMID:Repeated GH-releasing hormone administration unravels different GH secretory patterns in normal adults and children. 249 48


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