Evidence for a sex difference in the basal growth hormone response to GABAergic stimulation in humans

1988 ◽  
Vol 119 (3) ◽  
pp. 353-357 ◽  
Author(s):  
Palmiero Monteleone ◽  
Mario Maj ◽  
Michele Iovino ◽  
Luca Steardo

Abstract. Evidence has been provided supporting the existence of a sex-related difference in the GH secretion following different GH-releasing stimuli. Since pharmacological activation of the endogenous gamma-aminobutyric acid (GABA) system results in increased basal GH release in humans, the present study was undertaken to investigate whether a sex difference is present in the GH response to GABAergic stimulation. Sixteen healthy subjects (8 women and 8 men) received orally 10 mg of baclofen, the direct GABAB agonist which freely crosses the blood-brain barrier. Blood samples were collected before (T = −30 and 0) and 30, 60, 90, 120 and 180 min after the drug administration for plasma GH measurements. Following baclofen administration, plasma GH rose in healthy males (F = 19.417, P < 0.0001), but not in females (F = 1.67, NS). These results suggest that GABA modulation of human GH release is sex-dependent.

2019 ◽  
Vol 8 (5) ◽  
pp. 571
Author(s):  
Seung Hyun Kim ◽  
Namo Kim ◽  
Eui Hyun Kim ◽  
Sungmin Suh ◽  
Seung Ho Choi

Growth hormone (GH) secretion is regulated by various hormones or neurotransmitters, including gamma-aminobutyric acid. The aim of this study was to determine the propofol requirement in patients with GH-secreting pituitary tumors undergoing transsphenoidal surgery. General anesthesia was induced in 60 patients with GH-secreting tumors (GH group, n = 30) or nonfunctioning pituitary tumors (NF group, n = 30) using an effect-site target-controlled intravenous propofol infusion. The effect-site concentrations were recorded at both a loss of consciousness and a bispectral index (BIS) of 40, along with the effect-site concentration after extubation, during emergence from the anesthesia. The effect-site concentration of propofol was higher in the GH group than in the NF group at a loss of consciousness and a BIS of 40 (4.09 ± 0.81 vs. 3.58 ± 0.67, p = 0.009 and 6.23 ± 1.29 vs. 5.50 ± 1.13, p = 0.025, respectively) and immediately after extubation (1.60 ± 0.27 vs. 1.40 ± 0.41, p = 0.046). The total doses of propofol and remifentanil during anesthesia were comparable between the groups (127.56 ± 29.25 vs. 108.64 ± 43.16 µg/kg/min, p = 0.052 and 6.67 ± 2.89 vs. 7.05 ± 1.96 µg/kg/h, p = 0.550, respectively). The propofol requirement for the induction of a loss of consciousness and the achievement of a BIS of 40 is increased during the induction of general anesthesia in patients with GH-secreting tumors.


1984 ◽  
Vol 107 (1) ◽  
pp. 36-41 ◽  
Author(s):  
T. R. Hall ◽  
S. Harvey ◽  
A. Chadwick

Abstract. Anterior pituitary glands from chickens (Gallus domesticus) were incubated with or without single, mediobasal chicken hypothalami in medium containing histamine, alone or together with the antagonist diphenhydramine or in medium containing gamma-aminobutyric acid (GABA), alone or together with the antagonists bicuculline or picrotoxin. The release of prolactin (Prl) and growth hormone (GH) was measured by homologous radioimmunoassay. Histamine had no direct effect on the release of either hormone but stimulated Prl (in a dose-related way) and GH release when anterior pituitary glands were co-incubated with hypothalami. Diphenhydramine also had no direct effect on Prl or GH secretion but blocked the stimulatory effect of histamine on hypothalamusinduced Prl and GH release. When anterior pituitary glands were incubated without hypothalami, GABA, bicuculline and picrotoxin had no effect on the release of Prl or GH. However, GABA inhibited the release of both hormones in a concentration-related manner, when anterior pituitary glands were co-incubated with hypothalami. This inhibition was blocked by both bicuculline and picrotoxin. These results suggest that histamine and GABA may be involved in controlling the secretion of Prl and GH from the avian pituitary gland, possibly by modifying the secretion of hypothalamic releasing and/or release-inhibiting hormones.


1994 ◽  
Vol 131 (1) ◽  
pp. 50-55 ◽  
Author(s):  
V Coiro ◽  
R Volpi ◽  
ML Maffei ◽  
A Caiazza ◽  
G Caffarri ◽  
...  

Coiro V, Volpi R, Maffei ML, Caiazza A, Caffarri G, Capretti L, Colla R, Chiodera P. Opioid modulation of the gamma-aminobutyric acid-controlled inhibition of exercise-stimulated growth hormone and prolactin secretion in normal men. Eur J Endocrinol 1994;131:50–5. ISSN 0804–4643 The possible involvement of endogenous opioids in the gamma-aminobutyric acid-controlled (GABAergic) inhibition of growth hormone (GH) and prolactin (PRL) during physical exercise was evaluated in normal men. After fasting overnight, seven subjects were tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 15 min in all subjects. Tests were carried out under administration of placebo, the opioid antagonist naloxone (10 mg as an iv bolus injection), the GABAergic agonist sodium valproate (600 mg in three divided doses orally) or naloxone plus sodium valproate. During exercise, plasma GH and PRL levels rose 5.5- and 1.9-fold, respectively. The administration of naloxone did not modify, whereas sodium valproate significantly reduced the plasma GH and PRL rise during exercise. In the presence of sodium valproate, GH and PRL levels rose 3- and 1.5-fold, respectively, in response to exercise. When naloxone was given together with sodium valproate, both GH and PRL responses to exercise were abolished completely. These data suggest the involvement of a GABAergic mechanism in the regulation of GH and PRL responses to physical exercise in men. Furthermore, the data argue against a role of naloxone-sensitive endogenous opioids in the control of these hormonal responses to exercise, whereas they suggest a modulation by opioids of the GABAergic inhibitory action. Vittorio Coiro, Istituto di Clinica Medica Generale e Terapia Medica, Università di Parma, via Gramsci 14, 43100 Parma, Italy


1995 ◽  
Vol 132 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Massimo Scacchi ◽  
Cecilia Invitti ◽  
Angela I Pincelli ◽  
Claudio Pandolfi ◽  
Antonella Dubini ◽  
...  

Scacchi M, Invitti C, Pincelli AI, Pandolfi C, Dubini A, Cavagnini F. Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa. Eur J Endocrinol 1995;132:152–8. ISSN 0804–4643 High plasma growth hormone (GH) levels, associated with abnormal hormone responses to provocative stimuli, point to an altered GH secretion in anorexia nervosa. The GH-releasing effect of acutely administered glucocorticoids, firmly established in normal subjects, has not been reported in these patients. In this study, acute iv administration of 4 mg of dexamethasone, compared with saline, increased plasma GH in nine normal-weight women (AUC 848.2 ± 127.95 vs 242.8 ± 55.35 μg·l−1·min−1, p < 0.05, respectively) but was ineffective in 11 anorectic patients (AUC 3271.8 ± 1407.11 vs 2780.0 ± 1162.04 μg·l−1·min−1, NS). After dexamethasone, a significant lowering of plasma cortisol was observed in normal women (AUC 25367.0 ± 3128.43 vs 47347.1 ± 4456.61 nmol·l−1·min−1, after dexamethasone and saline, respectively, p < 0.05), but not in anorectic patients (AUC 77809.3 ± 8499.92 vs 78454.9 ± 7603.62 nmol·l−1·min−1, NS). In both groups, plasma adrenocorticotrophin (ACTH) displayed a significant decrease after dexamethasone (AUC 523.6 ± 92.08 vs 874.2 ± 115.03 pmol·l−1·min−1, p < 0.05, after dexamethasone and saline, respectively, in anorectic patients and 377.5 ± 38.41 vs 1004.9 ± 200.51 pmol·l−1·min−1, p < 0.05, in controls). However, when considering the hormonal decremental areas, a significant dexamethasone-induced ACTH inhibition, compared to saline, was evidenced in normal (ΔAUC –414.4 ± 65.75 vs 222.9 ± 42.40 pmol·l−1·min−1, p < 0.05) but not in anorectic women (ΔAUC –254.2 ± 96.92 vs 2.9 ± 132.32 pmol·l−1·min−1, NS). In conclusion, compared to normal subjects, anorectic patients do not display an increase of plasma GH levels and show a lower degree of inhibition of the hypothalamic–pituitary–adrenal axis following acute iv administration of dexamethasone. This observation broadens the array of the abnormal GH responses to provocative stimuli in anorexia nervosa and supports the existence, in these patients, of a decreased hypothalamic somatostatin secretion, although the possibility of a reduced tissue sensitivity to glucocorticoids cannot be excluded. Francesco Cavagnini, 2nd Chair of Endocrinology, University of Milan, Istituto Scientifico Ospedale San Luca, Centro Auxologico Italiano, via Spagnoletto 3, 20149 Milano, Italy


1993 ◽  
Vol 128 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Maria N Moreira-Andrés ◽  
Francisco J Cañizo ◽  
Federico Hawkins

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.


1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy


2001 ◽  
Vol 280 (3) ◽  
pp. E489-E495 ◽  
Author(s):  
Eleni V. Dimaraki ◽  
Craig A. Jaffe ◽  
Roberta Demott-Friberg ◽  
Mary Russell-Aulet ◽  
Cyril Y. Bowers ◽  
...  

To test whether endogenous hypothalamic somatostatin (SRIH) fluctuations are playing a role in the generation of growth hormone (GH) pulses, continuous subcutaneous octreotide infusion (16 μg/h) was used to create constant supraphysiological somatostatinergic tone. Six healthy postmenopausal women (age 67 ± 3 yr, body mass index 24.7 ± 1.2 kg/m2) were studied during normal saline and octreotide infusion providing stable plasma octreotide levels of 2,567 ± 37 pg/ml. Blood samples were obtained every 10 min for 24 h, and plasma GH was measured with a sensitive chemiluminometric assay. Octreotide infusion suppressed 24-h mean GH by 84 ± 3% ( P = 0.00026), GH pulse amplitude by 90 ± 3% ( P = 0.00031), and trough GH by 54 ± 5% ( P = 0.0012), whereas GH pulse frequency remained unchanged. The response of GH to GH-releasing hormone (GHRH) was not suppressed, and the GH response to GH-releasing peptide-6 (GHRP-6) was unaffected. We conclude that, in women, periodic declines in hypothalamic SRIH secretion are not the driving force of endogenous GH pulses, which are most likely due to episodic release of GHRH and/or the endogenous GHRP-like ligand.


2001 ◽  
Vol 280 (1) ◽  
pp. R225-R232 ◽  
Author(s):  
Janneke G. Langendonk ◽  
Johannes D. Veldhuis ◽  
Jacobus Burggraaf ◽  
Rik C. Schoemaker ◽  
Adam F. Cohen ◽  
...  

We compared four common mathematical techniques to determine daily endogenous growth hormone (GH) secretion rates from diurnal plasma GH concentration profiles in 24 women (16 upper- or lower-body obese and 8 normal-weight individuals). Two forms of deconvolution analysis and two techniques based on a priori determined GH clearance estimates were employed. Deconvolution analyses revealed significant differences in the 24-h GH secretion rate between normal-weight and upper-body obese women, whereas the other two techniques did not. Moreover, deconvolution analyses predicted that the reduction in mean plasma GH concentrations in upper-body obese women was accounted for by impaired GH secretion, whereas the other methods suggested that obesity increases GH metabolic clearance. Thus we infer that disparate conclusions concerning GH secretion can be drawn from the same primary data set. The different inferences likely reflect dissimilar kinetic assumptions and the particular limitations intrinsic to each analytical approach. Accordingly, we urge caution in the facile comparison of calculated GH secretion data in humans, especially when kinetic and secretion measurements are performed under different conditions. The most appropriate way to determine the GH secretion rate in humans must be balanced by the exact intent of the experiment and the acceptability of different assumptions in that context.


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