Plasma Growth Hormone Response Research Articles

Inhibitory effect of circulating insulin on glucagon secretion during hypoglycemia in type I diabetic patients.

To clarify whether the circulating insulin level influences hormonal responses, glucagon secretion in particular, during hypoglycemia in patients with insulin-dependent (type I) diabetes. Nine type I diabetic patients were studied. During two separate experiments, hypoglycemia was induced by low-dose (244 pmol.kg-1.h-1) and high-dose (1034 pmol.kg-1.h-1) intravenous insulin infusions for 180 min in each case. The arterial blood glucose level was directly monitored every 1.5 min, and glucose was infused in the high-dose test to clamp the arterial blood glucose level to be identical as in the low-dose test. Despite the fact that the plasma insulin level was four times higher in the high-dose than in the low-dose test (740 +/- 50 vs. 180 +/- 14 pM), a close to identical arterial hypoglycemia of approximately 3.3 mM was obtained in the two experiments. During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237 +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 +/- 19 vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level. This study demonstrates that, in type I diabetic patients, the glucagon response to hypoglycemia is suppressed by a high level of circulating insulin within the physiological range. Our findings may help to explain the impairment of glucagon secretion during hypoglycemia frequently seen in these patients.

Effect of FSH-P priming on superovulatory response in buffalo (Bubalus bubalis)

The aim of this study was to determine the benefits of growth hormone-releasing factor (GRF) on growth and feed conversion efficiency (FCE) in buffaloes. Twelve Murrah buffalo heifers (Bubalus bubalis) of mean age 24.8 months and mean body weight 302.4 kg were divided into two groups (treatment and control) with six animals in each group. The buffaloes were given intravenous injections of bovine GRF (bGRF) at a dose rate of 10 μg/100 kg body weight or an equal volume of saline at 15-day intervals for a period of 9 months. Plasma growth hormone (GH) responses to bGRF challenge were measured in blood samples collected at 90-day intervals on days 1, 90, 180 and 270 and samples were taken at −60, −30, 0, +10, +20, +30, +60, +120 and +180 min relative to bGRF injection. Blood samples were also collected weekly by jugular venepuncture for the quantification of plasma GH. The average growth rate (AGR) and FCE of all animals were recorded at 15-day intervals.Plasma GH concentrations increased (P = 0.001) steadily following bGRF challenge, peaking 10–20 min after challenge and declining to baseline by 180 min. In the treatment group, there were no significant differences (P > 0.05) in either the peak heights of the GH response or the area under the curve (AUC) of the GH response after bGRF challenge on any of the four occasions of intensive bleeding. There were overall increases in plasma GH concentrations (P < 0.01), AGR (P < 0.01) and FCE (P = 0.05) in the treatment group compared with the control animals. The study showed that GH responsiveness to administration of bGRF at 15-day intervals over 9 months of treatment remained unchanged in buffalo heifers. Exogenous bGRF treatment for a long period can therefore enhance GH release leading to higher growth rates and better feed conversion efficiency in buffalo heifers.

Serum thyrotropin response to combined arginine and thyrotropin-releasing hormone administration provides evidence for an altered somatostatinergic tone in acromegaly.

The aim of this study was to evaluate plasma thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) responses to the TSH-releasing hormone (TRH) test and to a combined arginine-TRH test (ATT-TRH) in 10 normal subjects and in 15 acromegalic patients. In controls, TSH responsiveness to TRH was enhanced by ATT (p less than 0.001). When considering the 15 acromegalic patients as a whole, no significant difference in TSH responses was detected during the two tests. However, patients without suppression of plasma GH levels after oral glucose load showed an increased TSH responsiveness to the ATT-TRH test if compared to TRH alone (p less than 0.025), while patients with partial suppression of plasma GH levels after glucose ingestion showed a decreased TSH responsiveness to ATT-TRH (p less than 0.05). No difference was recorded in PRL and GH responses, evaluated as area under the curve, during TRH or ATT-TRH tests in controls and in acromegalics. In conclusion, (1) normal subjects have an enhanced TSH response to the ATT-TRH test and (2) acromegalic patients without suppression of GH levels after oral glucose load show a TSH responsiveness to the ATT-TRH test similar to that of controls, while acromegalics with partial GH suppression after oral glucose load have a decreased TSH responsiveness to the ATT-TRH test. These data suggest that acromegaly is a heterogeneous disease as far as the somatostatinergic tone is concerned.

Plasma growth hormone and prolactin responses to graded levels of acute exercise and to a lactate infusion.

The effect of acute exercise at three graded intensities on plasma growth hormone (GH) and prolactin (PRL) concentrations was examined in three groups of healthy male volunteers. According to their training status these subjects were divided into untrained, moderately trained and highly trained. A clear response of GH to exercise was registered already at an intensity of 50% of maximal oxygen uptake (VO2max) with a maximal response at 70% VO2max and no further effect at 90% VO2max. In contrast, no PRL response was observed at 50% VO2max, a small PRL rise was seen at 70% VO2max and the highest response occurred at 90% VO2max. Basal and exercise-stimulated plasma GH and PRL concentrations were similar in the three groups tested at similar relative workloads, suggesting that physical training induces adaptive changes whereby higher absolute workloads induce similar hormonal and metabolic changes. To examine a potential causative role of lactate in inducing the GH and PRL responses, sodium L-lactate was infused intravenously to normal sedentary volunteers at doses producing plasma lactate concentrations within the range of those seen between 70 and 90% VO2max. This resulted in a significant elevation of plasma GH and PRL concentrations, which, however, were smaller than those obtained at an exercise-induced matched plasma lactate concentration. We conclude that physical training causes adaptive changes in highly trained runners so that identical GH and PRL responses to exercise are recorded at higher absolute workloads. Lactate may be involved in the exercise-induced GH and PRL response; however, it does not appear to play an exclusive role.

Hypothalamic regulation of impaired growth hormone secretion in diabetic rats. 1. Studies in streptozotocin-induced diabetic rats.

Growth hormone (GH) secretion is blunted in diabetic rats. In the present experiment we observed that pituitary GH concentrations and the plasma GH response to an exogenous dose of growth hormone-releasing hormone (GHRH) is decreased in streptozotocin-induced diabetic rats (p less than 0.02) with respect to normal rats. In an attempt to determine if increased somatostatin (SRIF) secretion is responsible for the decreased GH secretion, we studied the effect of modulating SRIF tone on the GH response to GHRH in normal and streptozotocin-induced diabetic rats. Rats were pretreated with either normal sheep serum and saline (NSS+SAL), somatostatin antibodies (SRIF-Ab), or pyridostigmine (PD), an acetylcholinesterase inhibitor hypothesized to reduce hypothalamic SRIF secretion. Pretreatment of normal rats with SRIF-Ab or PD resulted in an increased GH response to exogenous GHRH in comparison to NSS+SAL-pretreated normal rats at 5 min postinjection. In contrast, pretreatment of diabetic rats with SRIF-Ab or PD did not alter the GH response to exogenous GHRH when compared to NSS+SAL-pretreated diabetic animals. These results suggest that the blunted GH response to exogenous GHRH observed in streptozotocin-induced diabetic rats may not be due to an increase of endogenous SRIF tone.

Age-related decrease in plasma growth hormone: Response to growth hormone-releasing hormone, arginine, and l-dopa in obesity

Aging is associated with a reduction in plasma growth hormone (GH) secretion in non-obese subjects. To determine whether or not age-related changes in plasma GH secretion exist in obese subjects, we measured (a) plasma GH response to growth hormone-releasing hormone (GRH; 1 μg/kg body wt), arginine (0.5 g/kg body wt), l-dopa (500mg), and (b) plasma glucose, insulin, and free fatty acids (FFAs) in 26 fasted obese subjects of various ages ranging from 16 to 71 years. Only subjects with a body mass index (BMI; kg/m 2) between 30.0 and 39.0 were studied. Six subjects were adolescents, 9 were in their 20s, and 11 were 30 years or older. The mean peak levels of plasma GH in response to GRH, arginine, and l-dopa in obese subjects were 11.3 ± 2.1, 21.9 ± 4.4, and 5.2 ± 0.3 ng/mL in adolescents, 8.2 ± 1.6, 9.1 ± 1.5, and 3.1 ± 0.6 ng/mL in those in their 20s, and 4.5 ± 0.4, 7.3 ± 1.4, and 2.8 ± 0.3 ng/mL in those 30 years or older, respectively, showing a significant decrease in peak GH level with advancing age ( P < .05 to P < .01). There was a negative correlation between the logarithmic increase in age and the peak GH response to GRH ( r = −.635, P < .01), arginine ( r = −.564, P < .01), and l -dopa ( r = −.630, P < .01), and between the logarithmic increase in age and the integrated GH response to GRH ( r = −.564, P < .01), arginine ( r = −.612, P < .01), and l-dopa ( r = −.551, P < .01) in all subjects. Plasma glucose, insulin, and FFAs did not change with age. There was no correlation between the peak GH level or the integrated GH response to these three stimuli and the plasma levels of glucose, insulin, and FFAs, respectively. Our findings suggest that in obese subjects advancing age reduces the secretory responsiveness of pituitary somatotropes to these three stimuli.

Human insulin and awareness of acute hypoglycaemic symptoms in insulin-dependent diabetes

Some insulin-dependent diabetic patients who have clear symptoms of hypoglycaemia during animal insulin treatment have reported loss of these symptoms when human insulin preparations are introduced. A survey of Mersey Region, UK, identified eleven patients whose awareness of hypoglycaemia was lost after introduction of human insulin but returned with animal insulin treatment; seven took part in the study. Acute hypoglycaemia was induced in these patients on two occasions by intravenous infusion of porcine or human soluble insulin (2·5 mU. kg -1, min -1) in random order. There was no significant difference between porcine and soluble insulin in the plasma glucose profile; mean (SEM) plasma glucose fell from 7·1 (0·4) mmol/l to a nadir of 1·5 (0·1) mmol/l with porcine insulin and from 7·1 (0·5) mmol/l to 1·6 (0·2) mmol/l with human insulin. An acute autonomic reaction occurred in all seven patients, at a similar plasma glucose concentration (1·9 [0·1] mmol/l with porcine insulin; 2·0 [0·2] mmol/l with human insulin). There were no significant differences in the frequency of symptoms or signs of hypoglycaemia between the two insulin species, nor any consistent differences in plasma glucagon, cortisol, growth hormone, adrenaline, or noradrenaline responses to hypoglycaemia. Symptomatic and hormonal responses to acute hypoglycaemia induced by porcine and human soluble insulins therefore seem to be almost indistinguishable, even in patients carefully selected for their apparent loss of hypoglycaemia awareness with human insulin.

Noonan's Syndrome: Abnormalities of the Growth Hormone/IGF‐I Axis and the Response to Treatment with Human Biosynthetic Growth Hormone

Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5-12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.

Blunted Growth Hormone Response to Clonidine in Patients With Generalized Anxiety Disorder

Patients with panic disorder or depression have abnormal responses to the alpha 2-adrenergic receptor partial agonist clonidine. Evidence linking anxiety to noradrenergic dysfunction and the presence of anxiety symptoms in both depression and panic suggest that abnormal responses to clonidine in these disorders could be due to the anxiety symptoms. To explore a possible link between "nonspecific" anxiety symptoms and abnormal responses to clonidine, patients with DSM-III-defined generalized anxiety disorder were given intravenous infusions of clonidine hydrochloride. Responses of plasma growth hormone, 3-methoxy-4-hydroxyphenylglycol, heart rate, blood pressure, and psychological states were determined in 11 patients with generalized anxiety disorder and 14 healthy subjects. Clonidine produced significantly smaller growth hormone responses in patients than in healthy controls. The two groups did not differ in 3-methoxy-4-hydroxyphenylglycol, heart rate, blood pressure, or psychological responses to clonidine. These results are compared with data from similar studies on patients with panic disorder and depression. The blunting of the growth hormone response to clonidine in all three disorders could be due to the presence of generalized anxiety symptoms. Subsensitivity of postsynaptic alpha 2-adrenoreceptors may be present in all three disorders; however, there are alternative interpretations of growth hormone blunting in response to clonidine. Blunting was observed in DSM-III-defined generalized anxiety disorder, whether or not the DSM-III-R criterion of excessive worry was also present.

Thyrotropin Releasing Hormone(TRH)-Induced Release of 7B2 (A Neuroendocrine Polypeptide) In Vivo and In Vitro Using Adenoma Cells of a Patient with Acromegaly.

We demonstrated TRH-induced release of 7B2 (a neuroendocrine polypeptide) in vivo and in vitro (somatotroph adenoma cells) in a patient with acromegaly. The mean basal plasma 7B2 and growth hormone (GH) levels before operation were 142.8 +/- 3.2 ng/l and 52.4 +/- 1.6 micrograms/l (mean +/- SEM), respectively and these levels significantly rose after an i.v. administration of 500 micrograms of thyrotropin releasing hormone (TRH). After the transsphenoidal adenomectomy, the basal level of plasma GH was restored to the normal level and that of plasma 7B2 was slightly decreased. In addition, TRH-induced response of plasma 7B2 and GH disappeared post-operatively. In a primary culture of somatotroph adenoma cells obtained at surgery, TRH significantly induced secretions of both 7B2 and GH. Immunohistochemical studies showed the positive 7B2 and GH immunoreactivities in somatotroph adenoma cells. These findings strongly suggest that the somatotroph adenoma cells in this case produced and released 7B2 concomitant with GH.

Growth Hormone (GH) Profiles with Successive Provocation by GH-releasing Hormone and Arginine in Children: A Clinical Appraisal.

To establish a single and reliable test for evaluating growth hormone (GH) secretion, we examined successive GH provocation by two agents with different modes of action, GH releasing-hormone (GHRH) and arginine (Arg) in 60 children of short stature, 6 patients with pituitary dwarfism and 9 normal young adults. Their GH profiles were qualitatively classified into 4 types: 25 children and 7 adults responded to both stimuli with 2 GH peaks (48.7 +/- 4.3 [SEM] micrograms/L for GHRH and 32.2 +/- 2.6 micrograms/L for Arg in children; 25.8 +/- 7.6 micrograms/L and 30.1 +/- 9.2 micrograms/L respectively in adults) (type A). A single peak for GHRH (57.7 +/- 4.6 micrograms/L) without an Arg-induced peak was obtained in 29 younger children (type B), which is considered to be a GHRH-dominant pattern. Two of them were diagnosed as hypothalamic GHRH deficiency based on a low nocturnal plasma GH and good response to GH treatment. Six adolescents and 2 adults showed a blunted response to GHRH (9.0 +/- 1.1 micrograms/L) but a normal response to Arg (40.6 +/- 9.5 micrograms/L) (type C), which appears to be caused by somatostatin (SRIH) hypertonicity. None with pituitary dwarfism responded to both stimuli (4.5 +/- 1.3 and 2.3 +/- 0.5 micrograms/L). Thus, the GHRH-Arg test makes it possible to evaluate the counterbalance between GHRH and SRIH as well as to differentiate pituitary GH deficiency from hypothalamic GHRH dysfunction.

Chronic Growth Hormone Administration Does Not Suppress Endogenous Growth Hormone Secretion in Patients with Neurosecretory Growth Hormone Dysfunction

Short children who respond normally to growth hormone (GH) stimulation, but have a subnormal spontaneous secretion of GH (neurosecretory GH dysfunction, NSD) are treated with exogenous GH which might suppress their endogenous GH secretion. The effect of chronic administration of GH (8-24 months) on plasma GH responses to GHRH, clonidine and spontaneous GH secretion were studied in 17 NSD patients. The diagnosis of NSD was based on a normal GH response to clonidine (greater than 10 micrograms/l) and an integrated concentration of (IC-GH) GH less than 3.2 micrograms/l. The GH dose used in this study was 0.25 IU/kg three times a week in 10 patients and 0.05 IU/kg daily in 7 patients. Insulin-like growth factor I levels (nmol) increased significantly on therapy from 9.3 +/- 3.8 to 24.4 +/- 22.4 (p less than 0.001). The GH response (microgram/l) to GHRH was 20.4 +/- 5.5 before treatment and 22.4 +/- 6.2 on GH. Peak GH after clonidine was 22.4 +/- 8.9 and 22.8 +/- 8.1, respectively. There was no significant decrease in the number of GH spontaneous peaks (1.8 +/- 0.7 vs. 2.0 +/- 0.7, respectively) or in the area under the curve. A subcutaneous GH bolus of 0.25 IU/kg in 4 patients resulted in a GH peak of 55-82 micrograms/l at 3-5 h and a gradual return to basal levels at 15-20 h after GH administration. The first spontaneous GH peak appeared 26-28 h after GH injection, peak amplitude was 10-15 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone (GH) secretion in the dwarf rat: release, clearance and responsiveness to GH-releasing factor and somatostatin

The new mutant GH-deficient dwarf (Dw) rat was used to study the effects of GH-releasing factor (GRF) or somatostatin (SRIF) on GH release. In anaesthetized adult Dw female rats, i.v. injections of GRF (0.031-2.0 micrograms) elicited a dose-dependent release of GH. Although the peak plasma GH responses to maximal GRF doses were much lower in adult Dw rats compared with normal rats of this strain (AS), the responses largely reflected their relative pituitary GH contents (140 +/- 17 micrograms vs 2.9 +/- 0.4 micrograms, AS vs Dw (means +/- S.E.M.), P less than 0.001). Except at 20 days of age, normal AS rats were more sensitive to GRF than Dw rats despite their larger body weight. Peak GH responses to injection of 31.25 ng GRF increased nine-fold in normal rats between 20 and 40 days, whereas the GH responses to this GRF dose diminished in Dw rats over this age range, and their pituitary GH content was only 2-5% of that of age-matched AS rats. Treatment with human GH (200 micrograms/day for 7 days) stimulated growth in 40-day-old Dw rats and slightly increased the GH response to a low dose of GRF. Basal GH levels in adult Dw animals were sevenfold lower than in AS rats (2.4 +/- 0.3 vs 17.6 +/- 3.3 micrograms/l P less than 0.001) and were further suppressed by i.v. infusion of SRIF (25 micrograms/h). As in normal rats, a rebound GH secretion occurred in Dw rats after stopping SRIF, which was blocked by injection of anti-GRF serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone and prolactin response to rehydration during exercise: effect of water and carbohydrate solutions

The effect of progressive rehydration with either water or a carbohydrate solution on the plasma growth hormone (GH) and prolactin (PRL) response to exercise was examined together with plasma somatostatin. Five subjects underwent four 3-h experimental sessions at 36 degrees C in which 25-min exercise periods alternated with 5-min rest periods. The sessions were conducted without fluid replacement (DH) or under rehydration with either water or isosmotic carbohydrate solutions AISO (acid) or NISO (neutral). The fluid was given every 10 min after the 1st h of exercise. Plasma GH increased significantly (p less than 0.01) under DH after 2 and 3 h of exercise; this increase was prevented by rehydration with water, AISO and NISO. Plasma glucose was significantly higher following AISO and NISO rehydration compared with DH. This possibly influenced the GH response, but there was no difference between plasma glucose levels under DH and water rehydration at any time. The solutions tended to attenuate the increase in heart rate, rectal temperature and plasma cortisol, suggesting that the lack of GH response under rehydration conditions is a result of decreasing physiological stress levels. The GH response could not be explained by plasma somatostatin, which tended to decline in all sessions. Plasma PRL did not increase in any of the sessions, confirming that exercise without rehydration is a more potent stimulator of GH than of PRL. It is concluded that progressive rehydration with water is sufficient to prevent the exercise-induced increase in plasma GH.

GABA, depression and the mechanism of action of antidepressant drugs: a neuroendocrine approach

Recent evidence has suggested the involvement of the GABAergic system in depression and in the mechanism of action of somatic antidepressant treatments. In particular, GABA B receptors have been found to be increased in the rat frontal cortex following chronic antidepressant therapies. In the present study, the sensitivity of GABA B binding sites was assessed in nine healthy men and 10 depressed patients via the plasma growth hormone (GH) response to acute baclofen administration (20 mg p.o.). Depressed subjects were tested before and after 15 and 35 days of treatment with amitriptyline (100 mg/day), imipramine (100 mg/day) and fluoxetine (20 mg/day). GH response to acute GABA B receptor activation did not differ between depressed subjects and healthy controls. Moreover, chronic antidepressant treatment did not significantly modify this response, even when a clear therapeutic effect was obtained. These results do not support the idea that GABAergic mechanisms are involved in the pathophysiology of depression and in the mechanism of action of antidepressant drugs.

Very-low-calorie diet-induced weight reduction reverses impaired growth hormone secretion response to growth hormone-releasing hormone, arginine, and l-dopa in obesity

To determine whether impaired growth hormone (GH) secretion in obese subjects is a consequence of obesity or a pre-existing pituitary-hypothalamic disorder, we measured (1) plasma GH response to growth hormone-releasing hormone (GRH; 1 μg/kg body weight [BW]), arginine (0.5 g/kg BW), and l-dopa (500 mg); and (2) plasma glucose, insulin, and free fatty acids (FFA) in obese subjects before and after weight reduction due to very-low-calorie diet therapy using Optifast (240 kcal/d for 8 to 12 weeks). Body weight and body mass index (BMI) values before and after weight reduction were 87.2 ± 4.1 kg and 34.5 ± 0.9 kg/m 2, and 67.8 ± 2.7 kg and 27.0 ± 0.4 kg/m 2, respectively. GH response to GRH, arginine, and l-dopa in obese subjects was markedly impaired before weight reduction, whereas significantly increased responses were noted after weight reduction ( P < .01). Impaired integrated GH response to GRH, arginine, and l-dopa in obese subjects was significantly restored after weight reduction ( P < .01). Plasma glucose levels did not change, while plasma insulin and FFA levels decreased significantly after weight reduction ( P < .01, P < .05). There was no significant correlation between integrated GH response to these three stimuli and plasma levels of glucose, insulin, and FFA, respectively. The reversibility of GH response to all three stimuli after weight reduction suggests that impaired GH secretion is a consequence of obesity rather than a pre-existing pituitary-hypothalamic disorder.

Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging

In 11 elderly normal subjects and in 17 young healthy subjects we studied the response of plasma growth hormone to GH-releasing hormone (GHRH(29), 1 microgram/kg iv) alone and preceded by pyridostigmine (120 mg orally 60 min before GHRH), a cholinesterase inhibitor likely able to suppress somatostatin release. The GH response to pyridostigmine alone was also examined. Basal plasma GH levels were similar in elderly and young subjects. In the elderly, GHRH induced a GH rise (AUC, median and range: 207.5, 43.5-444.0 micrograms.l-1.h-1) which was lower (p = 0.006) than that observed in young subjects (548.0, 112.5-2313.5 micrograms.l-1.h-1). The pyridostigmine-induced GH rise in the elderly was similar to that in young subjects (300.5, 163.0-470.0 vs 265.0, 33.0-514.5 micrograms.l-1.h-1). Pyridostigmine potentiated the GH responsiveness to GHRH in both elderly (437.5, 152.0-1815.5 micrograms.l-1.h-1; p = 0.01 vs GHRH alone) and young subjects (2140.0, 681.5-4429.5 micrograms.l-1.h-1; p = 0.0001 vs GHRH alone). However, the GH response to pyridostigmine + GHRH was significantly lower (p = 0.0001) in elderly than in young subjects. In conclusion, the cholinergic enhancement by pyridostigmine is able to potentiate the blunted GH response to GHRH in elderly subjects, inducing a GH increase similar to that observed after GHRH alone in young adults. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in normal aging. However, a decreased GH response to combined administration of pyridostigmine and GHRH in elderly subjects suggests that other abnormalities may coexist, leading to the secretory hypoactivity of somatotropes.

Neuroendocrine measures of dopaminergic function in chronic cocaine users

Plasma prolactin (PRL) and growth hormone (GH) levels are determined, in part, by the effects of dopamine (DA) at pituitary and hypothalamic DA receptors, respectively. To determine if chronic cocaine abuse alters dopaminergic activity, basal PRL and GH concentrations were measured in 16 male patients meeting DSM-III-R criteria for cocaine dependence (8 cocaine users and 8 cocaine + alcohol users) and 8 normal controls. In addition, the functional responsivity of DA receptors was assessed in the same group of patients by measuring the change in plasma PRL and GH concentration following the administration of the direct-acting DA agonist, apomorphine (0.01 mg/kg, s.c.) or saline. No difference in basal plasma PRL and GH levels or plasma PRL and GH responses to apomorphine administration was found between the entire group of cocaine patients and normal controls. However, three of the cocaine patients had basal plasma PRL levels that were more than 2.5 SD greater than that of the normal controls, suggesting that some interference of dopaminergic inhibition of PRL secretion might be present in at least some cocaine users. Although baseline plasma PRL levels were elevated in a subgroup of cocaine users, these data do not support the hypothesis that chronic cocaine abuse produces consistent abnormalities in dopaminergic function at the pituitary or hypothalamus.

Chronic antidepressant drug treatment does not affect GH response to baclofen in depressed subjects

The growth hormone (GH) response to baclofen, a specific GABAB agonist, was tested in 8 male depressed patients before and after chronic treatment with amitriptyline (100 mg/day). No difference was seen in plasma GH response before and 28 days after amitriptyline treatment, suggesting that chronic antidepressant drug treatment does not increase hypothalamic GABAB receptor sites in humans. These data suggest that further studies need to support the hypothesis of a GABA involvement in the mechanism of action of antidepressant drugs.

The Effect of Cyproheptadine on Plasma Growth Hormone (GH) and on Somatostatin Response to GH-Releasing Hormone in Man

Cyproheptadine (CPH)--a putative serotonin antagonist--is known to inhibit growth hormone (GH) response to various pharmacological stimuli, as well as during sleep. To elucidate the possible site at which this drug takes effect, we examined plasma GH and somatostatin response to i.v. GHRH1-44 (1 microgram/kg body wt.) before and after CPH treatment in 10 healthy volunteers. The oral administration of CPH (8-12 mg daily for 5 days; total dose 56 mg) significantly curbed GH response to GHRH as expressed in peak plasma GH values (32.0 +/- 6.1 micrograms/l vs. 12.6 +/- 3.2 micrograms/l; P less than 0.01) and in integrated GH response area (2368 +/- 517 micrograms x l-1 x 2 h vs. 744 +/- 172 micrograms x l-1 x 2 h; P less than 0.01). Plasma somatostatin levels did not change in response to GHRH.