Growth Hormone Secretion In Man Research Articles

Gonadal Status and Body Mass Index Jointly Determine Growth Hormone (GH)-Releasing Hormone/GH-Releasing Peptide Synergy in Healthy Men

Sex steroid hormones potentiate whereas increased body mass index (BMI) represses GH secretion. Whether sex steroids modify the negative effect of BMI on secretagogue-induced GH secretion in men is not known. The issue is important in designing GH-stimulation regimens that are relatively insensitive to both gonadal status and adiposity. Our objective was to compare the relationships between BMI and peptide-stimulated GH secretion in men with normal and reduced testosterone and estradiol availability. The study was performed at an academic medical center. Healthy young men were included in the study. Randomized separate-day iv infusion of saline and/or maximally effective doses of L-arginine/GHRH, L-arginine/GH-releasing peptide (GHRP)-2, and GHRH/GHRP-2 in eugonadal (n=12) and experimentally hypogonadal (n=10) men was performed. Regression of paired secretagogue-induced GH responses on BMI was determined. In eugonadal men, peak GH concentrations correlated negatively with BMI. In particular, BMI accounted for only 38% of the response variability after L-arginine/GHRH (P=0.0165), but 62% after GHRH/GHRP-2 (P=0.0012) and 65% after L-arginine/GHRP-2 (P=0.00075). In contrast, in hypogonadal men, GH responses were uncorrelated with BMI. The negative effects of BMI on peak GH responses in eugonadal and hypogonadal states differed most markedly after stimulation with GHRH/GHRP-2 (P=0.0019). This contrast was corroborated using integrated GH responses (P=0.0007). Short-term experimental gonadal sex hormone depletion attenuates dual secretagogue-stimulated GH secretion in lean young men. The inhibitory effect of relative adiposity on GH secretion appears to predominate over that of acute sex steroid withdrawal.

7 Interaction between body composition, leptin and growth hormone status

Administration of growth hormone (GH) induces changes in body composition, namely, increases in both bone and lean mass and a decrease in fatty tissue. However, the contrary issue, i.e. the way in which body composition affects the secretion of GH, is highly controversial. Disease states such as obesity and chronic hypercortisolism are associated with increased adiposity and/or the central distribution of fat. Ageing, characterized by excess adiposity, is also associated with impaired secretion of GH. In these states, both spontaneous and stimulated secretion of GH is severely impeded. At the other extreme, malnutrition and fasting are both associated with increased secretion of GH when confronted with most, if not all, stimuli. As the common factor in all of these situations is the increased or decreased adiposity, or the changes in energy homeostasis, it has been postulated that adipose tissue exerts a relevant role in the control of GH secretion in man. The link between adipose tissue and GH seems to be exerted through at least two signals produced by adipocytes: free fatty acids (FFA) and the recently cloned protein, leptin. An increase in FFA blocks secretion of GH, while a decrease in FFA enhances secretion. Leptin, a hormone whose main role is to regulate the intake of food and energy expenditure, seems to regulate GH secretion by acting at the hypothalamic level. In summary, body composition affects GH secretion by way of the degree of adiposity, and free fatty acids and leptin would appear to be the messages through which adipocytes participate in the regulation of GH secretion. This framework clarifies the metabolic control of GH, a hormone with profound metabolic activities.

Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH.

Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog

Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli; in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opiods induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline; (b) a met-enkephalin analog G-DAMME 250 micrograms IV as a bolus at time 0'; (c) hGH 2 IU as an IV bolus at time -180'; (d) G-DAMME as above, preceded by hGH as above. In our study, G-DAMME stimulated GH secretion both basally (peak 17.9 +/- 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 +/- 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded.

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay.

A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = -0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

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.

The effects of sumatriptan on pituitary secretion in man

Sumatriptan, a new antimigraine drug with high affinity and selectivity for certain 5-hydroxytryptamine (5-HT1D) receptor subtypes, was administered to 12 normal subjects, in order to investigate the effects of 5-HT receptor activation on anterior pituitary secretion. Sumatriptan increased plasma growth hormone (GH) levels from 2.5 +/- 0.5 mIU/l in basal conditions to 17.3 +/- 2.6 mIU/l 30 min after administration of the drug. After pre-treatment with cyproheptadine, an anti-serotoninergic drug known to inhibit GH secretion, the mean integrated sumatriptan-induced GH response decreased from 14.8 +/- 3.9 muI/l*hr to 3.7 +/- 1.7 mIU/l*hr. Sumatriptan administration did not have any effect on the secretion of the other anterior pituitary hormones. It is concluded that sumatriptan selectively increases GH secretion in man, but the exact nature of the receptors involved is not yet known.

Interaction of free fatty acids and arginine on growth hormone secretion in man

We studied the interaction between free fatty acids (FFAs) and arginine (ARG) on basal and growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in 14 normal subjects. Compared with placebo, ARG induced a significant increase of GH secretion (334.0 ± 157.5 v 36.9 ± 27.6 μg/L/h, P < .05). The increased levels of FFAs (1.9 ± 0.4 mEq/L), obtained by the infusion of a lipid-heparin emulsion, abolished the effect of ARG (55.8 ± 45.6 v 334.0 ± 157.5 μg/L/h, P < .05). GHRH-induced GH secretion was potentiated by ARG (2,009.9 ± 463.2 v 922.0 ± 244.4 μg/L/h, P < .05) and suppressed by lipid-heparin infusion (106.2 ± 28.3 v 922.0 ± 244.4 μg/L/h, P < .01). Moreover, the lipid-heparin infusion inhibited the potentiating effect of ARG on the GHRH-induced GH increase (527.9 ± 113.6 v 2,009.9 ± 463.2 μg/L/h, P < .01). These results confirm the strong inhibitory effect of FFAs on GH secretion, showing that they are even able to inhibit the potentiating effect of ARG on the GH response to GHRH. Since ARG likely acts via inhibition of hypothalamic somatostatin release, the inhibitory effect of FFAs on GH secretion could take place directly at the pituitary level and/ or at the hypothalamic level, counteracting the effect of ARG.

On the effects of human galanin in man.

Human galanin was recently isolated and sequenced and was found to differ from porcine galanin, hitherto used for studies in humans, in several important respects. We therefore synthesized and purified human galanin and infused it i.v. at a rate of 74 pmol.kg-1.min-1 into six healthy volunteers for 60 min during a hyperglycaemic clamp. The clamp was achieved by i.v. infusion of glucose at a rate which in a control experiment had been demonstrated to maintain the plasma glucose level at 12-13 mmol/l for 90 min. Galanin concentrations reached a plateau of approximately 1500 pmol/l throughout the infusion as opposed to pre-infusion and control levels of 20-30 pmol/l. The glucose levels obtained in the two experiments were indistinguishable. Plasma levels of C-peptide and insulin increased significantly in both experiments and the dynamic concentration curves were almost identical. Glucagon concentrations in plasma decreased significantly and similarly. Growth hormone levels, however, increased eight-fold during galanin infusions. Galanin was eliminated from plasma with a half-life of 3.7 +/- 0.4 min, similar to that of porcine galanin. It is concluded that human galanin powerfully stimulates growth hormone secretion in man, but has no effect on pancreatic endocrine secretion or glucose metabolism in the concentrations obtained in this study.

Dexamethasone‐induced growth hormone release: A dose‐response study

AbstractGlucocorticoids have recently been shown to acutely stimulate growth hormone secretion in man. The aim of our study was to investigate the acute effects of three graded doses of dexamethasone. Six healthy male volunteers received in random order placebo, 1, 2 or 4 mg of oral dexamethasone. Mean stimulated growth hormone levels were significantly higher after 2 and 4 mg of DEX than after 1 mg or placebo. We conclude that dexamethasone used in lower doses than previously reported appears to stimulate growth hormone release in a dose dependent manner.

Physiological levels of growth hormone fail to suppress growth hormone releasing hormone (1-29) NH2-stimulated growth hormone secretion in man.

We studied 11 normal adult males. Six subjects (Study A) received a bolus of saline or of 50 mU biosynthetic human growth hormone (r-hGH) or a one hour iv infusion of r-hGH (80 mU/h) in random order. On each occasion this was followed by an iv bolus of GHRH (1-29) NH2 (100 micrograms) 90 minutes after the first event. Five subjects (Study B) received a bolus iv injection of saline or of 500 mU r-hGH followed by iv GHRH (1-29) NH2 (100 micrograms) 90 minutes later. There was no significant difference in the serum GH concentrations achieved following the 50 mU bolus or iv infusion of r-hGH (range 5.6-67.0 mU/l). Higher concentrations of GH (mean +/- SE, 238.4 +/- 21.3 mU/l) were achieved with the 500 mU bolus of r-hGH. The peak GH responses to iv GH-RH (1-29) NH2 were similar in all instances. The most important factor determining the response to exogenous GHRH (1-29) NH2 was the serum GH concentration at the time that the GHRH (1-29) NH2 was administered and the mode of r-hGH administration (iv bolus or iv infusion). These data demonstrate that within the range of physiological serum GH concentrations the mode of presentation of GH (bolus or infusion) and GH secretory status are the most important factors in determining GH responsivity to GHRH. Under these circumstances GH would appear not to participate in a rapid-acting short-loop negative feedback mechanism in man as the response to exogenous GHRH was not attenuated.

Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man

Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man

Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man.

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To further characterize the effects and mechanism of action of GHRP-6 on GH secretion, we assessed in normal man plasma GH responses to that hexapeptide 1) alone and in combination with exogenous GH-releasing hormone (GHRH) administration, 2) in a state of high endogenous somatostatinergic tone after atropine administration, and 3) in a state of low endogenous somatostatinergic tone induced by the cholinergic receptor agonist drug pyridostigmine or after insulin-induced hypoglycemia. We found a similar increase in plasma GH levels after the administration of either GHRP-6 (1 microgram/kg) or GHRH (1 microgram/kg); the areas under the curve (AUC) were (mean +/- SEM) 973 +/- 181 and 821 +/- 139, respectively. After combined GHRP-6 and GHRH administration, GH responses were considerably greater than those after either compound alone (4412 +/- 842; P < 0.01). Administration of the cholinergic receptor antagonist atropine (1 mg, im) completely prevented the GH responses to GHRP-6 (area under the curve, 103 +/- 14 vs. 815 +/- 156, respectively). On the other hand, pyridostigmine, a cholinergic agonist, slightly increased GH responses to GHRP-6 (P < 0.01 when comparing the AUC after pyridostigmine administration of 1571 +/- 151 and the AUC after administration of GHRP-6 alone of 815 +/- 156). Finally, combined GHRP-6 and insulin administration induced a much greater increase in plasma GH levels (AUC, 4047 +/- 327) than insulin alone (1747 +/- 229; P < 0.05) or GHRP-6 alone (1248 +/- 376; P < 0.05). Our results lend support to the view that GHRP-6-induced GH secretion is exerted through a non-GHRH-dependent mechanism. Furthermore, the fact that enhancement of somatostatinergic tone with atropine completely prevented the GH responses to GHRP-6, while pyridostigmine and insulin-induced hypoglycemia, which increased plasma GH levels by inhibiting hypothalamic somatostatin release, increased the same response suggest that although GHRP-6-induced GH secretion is dependent on the endogenous somatostatinergic tone, the stimulatory effect of GHRP-6 on plasma GH levels is not mediated by a change in hypothalamic somatostatinergic tone.

Metabolic status and growth hormone secretion in man.

The metabolic state influences GH secretion and, in turn, GH secretion influences overall body metabolism. While these are distinct physiological entities, separation of these interrelated phenomena should be considered artificial since the overall result is an organism which retains functional capacity in the setting of a variety of circumstances.

Corticoid-induced growth hormone (GH) secretion in GH-deficient and normal children.

Acute administration of corticoids is a potent stimulus of GH secretion in man. To ascertain their mechanism and point of action as well as the suitability of this novel test in the diagnosis of GH-deficient states, normal controls and GH-deficient children were studied. They were selected based on auxological criteria and the GH response to provocative stimuli. The GH-deficient children presented a blunted GH (mean +/- SEM; microgram/L) discharge after insulin-induced hypoglycemia (2.9 +/- 0.4), propranolol-exercise (7.4 +/- 1.5), and clonidine (6.5 +/- 0.8) compared with values in the normal children (7.2 +/- 2.2, 15.8 +/- 2.4, and 15.6 +/- 1.8, respectively). As expected, GH-releasing hormone (GHRH)-induced GH discharge in GH-deficient children (33.2 +/- 4.9) was similar to that in the control children (35.1 +/- 6.0). Administration of 2 mg/m2 body surface dexamethasone, iv, to normal children induced, 3 h later, a mean GH peak of 14.1 +/- 1.2 micrograms/L. This was significantly higher that the corticoid-induced GH peak in GH-deficient children (6.7 +/- 1.1 micrograms/L). The corticoid-induced areas under the secretory curve were 1130 +/- 55 and 616 +/- 54 for the control and GH-deficient children, respectively. GH release in children after dexamethasone administration followed the pattern previously described for adults, i.e. there were no modifications of basal GH levels in the first 2 h, the GH peak appeared around the third hour, and the GH levels remained increased until the fourth hour after dexamethasone administration. Individually considered, practically all control children, but only 2 of 12 GH-deficient children, presented a dexamethasone-induced GH peak over the 10 micrograms/L level. In both normal and GH-deficient patients, corticoids appeared just as potent a stimulus as propranolol-exercise and clonidine, and more potent than hypoglycemia. This new stimulus showed a pattern similar to that of the hypothalamic stimuli, but clearly different with respect to the pituitary one (GHRH), suggesting that corticoids activate GH secretion by acting at hypothalamic level. In conclusion, acute administration of corticoids could be a suitable test in the diagnostic armamentaria of GH-deficient states.

Corticosteroids as a New Stimulus of Growth Hormone Secretion in Man

The blunted growth hormone (GH) response to stimulation tests in conditions of excessive cortisol secretion or administration is well known. This paper presents a dual action of glucocorticoids upon GH secretion. Acute administration of glucocorticoids is demonstrated to be a potent stimulus for GH release, while long-term exogenous and endogenous glucocorticoid excess depresses GH release in response to the GHRH-test. © 1992, Walter de Gruyter. All rights reserved.

The role of sexual steroids in the modulation of growth hormone (GH) secretion in humans

Sex steroids contribute to modulate GH secretion in man. However, both the exact locus and mechanism by which their actions are exerted still remain not clearly understood. We undertook a number of studies designed to ascertain: (1) whether or not sudden or chronic changes in circulating gonadal steroids may affect GH secretion in normal adults; and (2) the reason(s) for gender-related dimorphic pattern of GH release. The pituitary reserve of GH, as evaluated by means of a GHRH challenge, was similar in women with anorexia nervosa and in normally menstruating women. Estrogenic receptor blockade with tamoxifen (TMX) did not significantly change GHRH-induced GH response in these normal women. Therefore, acute or chronic hypoestrogenism apparently had no important effects at level of somatotrophs. In another group of normal women we tested the possibility that changes in circulating estrogens might induce changes in the hypothalamic-somatotroph rhythm (HSR). GHRH challenges were performed throughout a menstrual cycle, and again after having achieved functional ovarian blockade with a GnRH agonist treatment. Short-term ovarian blockade did not significantly affect the parameters of GH response to GHRH, although it was accompanied by an increase in the number of women in a refractory HSR phase at testing. This suggested a low potentiating effect on the basic pattern of somatostatin (SS) release occurring as a consequence of the decrease in circulating estrogens. In normal men, neither the GH response to GHRH nor the HSR were affected by functional testicular blockade (after GnRH agonist treatment). However, the administration of testosterone enanthate (250 mg) to another group of men increased both the GHRH-induced GH release and the number of subjects in a spontaneous secretory HSR phase at testing; these were reversed by estrogenic receptor blockade with TMS. In another group of normal men, the fraction of GH secreted in pulses (FGHP) during a nocturnal sampling period was significantly decreased by testicular blockade. Other parameters of GH secretion, such as the number of GH pulses and their mean amplitude (A), and the mean plasma GH concentration (MCGH), showed a slight, although not significant, decrease following the lack of androgens. The administration of testosterone enanthate (500 mg) reversed these parameters to values similar to those in the basal study. Interestingly, when tamoxifen was given after testosterone enanthate, A, MCGH and FGHP increased to values significantly higher than in any other experimental condition in that study. In all, these data suggest that 17β-estradiol may participate in GH modulation by inhibiting the hypothalamic release of somatostatin, while testosterone stimulates it. The results obtained after estrogenic receptor blockade appear to indicate that the effect of testosterone in such a modulation is dependent on its aromatization to 17β-estradiol. The differential levels of this steroid in both sexes might account for the sexual dimorphic pattern of GH secretion. From other data in the literature, obtained in rats, and our preliminary data in children with constitutional delay of growth and puberty, it is tempting to speculate that the effect of 17β-estradiol may be exerted by modifying the functional activity of α-2 adrenergic pathways involved in the negative modulation of SS release.

Effects of Alpha‐ and Beta‐Adrenergic Agonists and Antagonists on Growth Hormone Secretion in Man

Abstract It is well known that the adrenergic system has both stimulatory and inhibitory influences on growth hormone (GH) secretion probably by modulating GH-releasing hormone (GHRH) and/or somatostatin release. To better understand the mechanisms by which these influences take place, we investigated the effects of alpha- and beta-adrenergic agonists and antagonists on both basal and GHRH-induced GH release in 23 male adult volunteers. The GH-releasing effect of clonidine (0.15 mg infused iv over 10 min), an alpha(2)-adrenergic agonist, was significantly blunted by yohimbine (30 mg orally at -50 min), a relatively specific alpha(2)-adrenergic antagonist area under the response curve, mean+/-SEM: 672.6 +/- 143.0 versus 219.6 +/- 16.7 mug/l/h; P<0.05). On the other hand, the GHRH (1 mug/kg iv as a bolus)-induced GH increase was unaffected by yohimbine (339.3 +/- 19.1 versus 518.1+/-172.8 mug/I/h). Concomitant blockade of alpha(1)-/alpha(2)-adrenoreceptors by phentolamine (0.5 mg/ml/min infused iv from -60 to +30 min) abolished the GHRH-induced GH rise (645.5+/- 106.0 versus 189.0+/-58.8 mug/l/h; P<0.01). Finally, the GHRH-stimulated release was blunted by beta(2)-adrenergic stimulation with salbutamol (10 mug/min infused iv from -5 to +15 min) (324.3 +/- 99.7 versus 112.7 +/- 48.8 mug/l/h; P<0.02). 1) The evidence that yohimbine is able to blunt the clonidine-induced GH release but fails to inhibit the GHRH-induced GH rise indicates that, as in animals, in man too the GH-releasing effect of clonidine is specifically mediated by alpha(2)-receptor activation, and may occur via endogenous GHRH release; 2) the inhibitory effect on GH release of beta, namely beta(2), receptor activation is probably mediated by the somatostatinergic system; 3) an unopposed beta-adrenergic activation would account for the inhibitory effect on GHRH-induced GH release of concomitant alpha(1)-/alpha(2)-adrenoreceptor blockade by phentolamine.

Acute Administration of Corticoids: A New and Peculiar Stimulus of Growth Hormone Secretion in Man*

It is widely accepted that chronic administration of corticoids in man inhibits the GH response to all of the stimuli tested so far. To study the action of corticoids administered acutely, several dexamethasone challenge tests were performed, after which GH levels were measured for 7 h. In eight volunteers, administration of 4 mg dexamethasone (Dex), iv, induced a clear-cut GH release compared with saline administration. The secretion followed an unusual pattern; basal GH levels (1.5 +/- 0.1 micrograms/L) started rising 2 h after Dex injection, reaching a peak of 17.5 +/- 4.4 micrograms/L after 3 or 3.5 h. Peak levels were maintained until 5 h post-Dex and decreased thereafter. Similar data were obtained when Dex was administered to five volunteers at the dose of 8 mg, orally, with a 30-min delay of the GH peak (19.6 +/- 7.9 micrograms/L). To study whether there was a cholinergic input responsible for the Dex action, another group of eight volunteers underwent three Dex tests (4 mg, iv) on three occasions, followed 90 min later by the administration of placebo (control), atropine (0.5 mg, iv), or pyridostigmine (120 mg, orally). The Dex-induced GH peak (20.8 +/- 5.2 micrograms/L) was not significantly increased by pyridostigmine (cholinergic agonist) treatment (24.2 +/- 4.0 micrograms/L). The blockade of muscarinic receptors by atropine induced a delay in the Dex-induced secretory peak, which appeared at 5 h. However, the Dex-atropine GH peak (14.9 +/- 4.1 micrograms/L) was not different from the Dex-placebo one. In conclusion, Dex alone is able to induce a clear-cut GH secretion in man. The stimulus followed a peculiar time pattern, with peaks levels attained 3 h after either iv or oral administration.