Plasma GH responses to human GHRH-antagonist in normal subjects

1996 ◽  
Vol 134 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Kunihiko Hanew ◽  
Aki Tanaka ◽  
Atsushi Utsumi ◽  
Akira Sugawara ◽  
Keishi Abe

Hanew K, Tanaka A, Utsumi A, Sugawara A, Abe K, Plasma GH responses to human GHRH-antagonist in normal subjects. Eur J Endocrinol 1996;134:67–72. ISSN 0804–4643 The effect of GHRH-antagonist {N-Ac-Tyr1, d-Arg2) GRF-(1–29)-NH2} on plasma GH morning and evening secretion was evaluated in 14 normal subjects (10 males, 4 females, aged 19–25 years). Plasma GH was determined using a high sensitivity IRMA kit (detection limit, 0.006 μg/l). After intravenous infusion of GHRH-antagonist (100 μg/100 ml saline over 75 min) in the morning, plasma GH remained constant during the 150 min post-infusion (N = 6). In contrast, when GHRH-antagonist was administered in the evening, plasma GH showed a clear and gradual decrease through the initial 90 min and returned to baseline levels at 150 min. Plasma GH values were also significantly lower from 75 min to 135 min when compared to physiological fluctuations in plasma GH (P < 0.05). Other anterior pituitary hormones remained unaffected by GHRH-antagonist. In conclusion, our data suggest that evening basal GH secretion, but not morning GH secretion, is maintained by endogenous GHRH. K Hanew, The Second Department of Internal Medicine, Tohoku University School of Medicine. 1-1 Seiryocho, Sendai 980, Japan

1990 ◽  
Vol 123 (2) ◽  
pp. 169-173 ◽  
Author(s):  
E. Ghigo ◽  
S. Goffi ◽  
E. Arvat ◽  
M. Nicolosi ◽  
M. Procopio ◽  
...  

Abstract. 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 μg/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 μg · 1−1 · h−1) which was lower (p = 0.006) than that observed in young subjects (548.0, 112.5-2313.5 μg · 1−1 · 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 μg · 1−1 · h−1). Pyridostigmine potentiated the GH responsiveness to GHRH in both elderly (437.5, 152.0-1815.5 μg · 1−1 · h−1; p = 0.01 vs GHRH alone) and young subjects (2140.0, 681.5-4429.5 μg · 1−1 · 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.


1993 ◽  
Vol 128 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Andrea Giustina ◽  
Mauro Doga ◽  
A Rosa Bussi ◽  
Massimo Licini ◽  
Maurizio Schettino

Galanin elicits growth hormone (GH) secretion in normal man but may cause a paradoxical fall of GH in acromegaly. The aim of our study was to investigate the effects of long-term treatment with bromocriptine on the galanin-induced GH decrease in acromegalic subjects. Six acromegalic patients (5F, 1M) chronically treated with bromocriptine underwent in randomized order: (i) iv infusion of 100 ml saline from 0 to 45 min and (ii) iv infusion of synthetic porcine galanin (0.5 mg in 100ml saline) from 0 to 45 min. In acromegalic patients, GH values fell from baseline (10.5±2.7 μg/1) to a mean nadir of 6.9±2.2 μg/1 after galanin infusion (57.8±9.4% vs basal levels). Saline infusion did not cause any change in circulating GH levels. The mean change in GH values with respect to baseline after galanin in these subjects significantly differed from that observed after saline from time 15 to 90 min. Serum prolactin levels were not significantly affected by galanin. Our results confirm that the dose of galanin capable of increasing plasma GH levels in normal subjects can decrease GH values in patients with acromegaly. Moreover, our data show that this paradoxical GH decrease induced by galanin can also be observed in patients chronically treated with bromocriptine. Therefore, the paradoxical decreasing effect of galanin on plasma GH levels in acromegaly seems not to be mediated via dopaminergic pathways.


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


2002 ◽  
pp. 761-766 ◽  
Author(s):  
D Micic ◽  
D Macut ◽  
M Sumarac-Dumanovic ◽  
A Kendereski ◽  
V Popovic ◽  
...  

OBJECTIVE: GH secretagogues and GH-releasing hormone (GHRH) exert a complex cross-talk at the somatotrope cell, and undertake homologous and heterologous desensitization. On the other hand, the discovery of ghrelin as a new factor implicated in the regulation of GH secretion makes a thorough assessment of its properties and cell biology processes mandatory. In order to implement this, three different testing schedules were devised using the administration, on the same day, of two GH stimuli administered in sequential order 120 min apart. The two aims of the study were (a) to evaluate the relative potency of ghrelin in comparison with other GH stimulants and (b) to assess the presence of homologous or heterologous desensitization between these compounds. DESIGN: The different testing days performed in random order were (a) on one day, saline was administered at time 0 min and ghrelin at time 120 min, (b) on another testing day, GHRH was administered at 0 min followed by ghrelin at 120 min and (c) on the last testing day, GH-releasing peptide-6 (GHRP-6) and ghrelin were injected at 0 and 120 min respectively. Ghrelin, GHRH and GHRP-6 were always administered at 1 microg/kg i.v., and plasma GH was measured. PATIENTS: Six normal subjects participated in the study after providing informed consent, and each was assessed on three different testing days, at least 1 week apart. RESULTS: Saline did not modify peak GH (means+/-s.e.) values (1.5+/-0.6 microg/l), and ghrelin administered 120 min later induced a significant GH rise (39.9+/-2.8 microg/l). On a different testing day, GHRH induced a GH peak (9.4+/-2.8 microg/l) lower than that of ghrelin injected 120 min later (26.8+/-4.7 microg/l). On the last testing day, GHRP-6 at time 0 induced a GH peak of 18.4+/-5.9 microg/l and ghrelin 120 min later a peak of 19.8+/-2.9 microg/l. The ghrelin-mediated GH secretion after GHRP-6 was significantly lower than the GH elicited by ghrelin when the preceding administration was saline. This demonstrated that ghrelin was partially affected by GHRP-6 and was not affected by GHRH. CONCLUSIONS: Calculated at equal mass doses or in molecular terms, ghrelin appears to be a more potent stimulus than GHRP-6 and GHRH. Ghrelin was completely insensitive to the previous administration of GHRH as well as relatively resistant to the homologous desensitization exerted by GHRP-6.


1991 ◽  
Vol 130 (1) ◽  
pp. 141-149 ◽  
Author(s):  
D. B. Dunger ◽  
D. R. Matthews ◽  
J. A. Edge ◽  
J. Jones ◽  
M. A. Preece

ABSTRACT The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00–08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9·1–20·9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization. The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150–180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30–75 min (r = 0·32; P < 0·001) and 30 min (r = 0·47; P < 0·0001) respectively. Generally, LH and prolactin pulses were in phase (r = 0·42; P < 0·0001) and there was a highly significant correlation (r = 0·64; P < 0·0001) between FSH and LH pulsatility. Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150–180 min was established and there was remarkable temporal coupling of pulsatility. Journal of Endocrinology (1991) 130, 141–149


2004 ◽  
pp. 447-450 ◽  
Author(s):  
R Takeno ◽  
Y Okimura ◽  
G Iguchi ◽  
M Kishimoto ◽  
T Kudo ◽  
...  

OBJECTIVE: Ghrelin is a potent peptide stimulating GH secretion. Besides its direct action on the pituitary, ghrelin has been reported to stimulate GH release via the vagal afferent nerve in rats. To examine the involvement of vagal nerve in ghrelin-induced GH secretion in humans, GH responses to ghrelin were compared between vagotomized patients with gastrectomy and normal subjects. METHODS: Ghrelin (0.2 microg/kg) or GHRH (1 microg/kg) was administered intravenously in vagotomized patients and normal subjects on separate days, and plasma GH responses to the stimuli were examined. RESULTS: Ghrelin caused a significant plasma GH rise in both vagotomized patients and normal subjects. Peak GH levels in vagotomized patients (37.5+/-16.9 ng/ml) were not different from those in normal subjects (29.9+/-23.1 ng/ml). The areas under the curve of GH response to ghrelin did not differ between the two groups. GHRH also increased GH levels, and peak GH levels and areas under the curve after GHRH stimulation were also comparable between vagotomized patients and normal subjects. CONCLUSIONS: In the present study, the involvement of the afferent vagal nerve in ghrelin-induced GH secretion was not confirmed in humans.


Author(s):  
S. Jalalah ◽  
K. Kovacs ◽  
E. Horvath

Lactotrophs, as many other endocrine cells, change their morphology in response to factors influencing their secretory activity. Secretion of prolactin (PRL) from lactotrophs, like that of other anterior pituitary hormones, is under the control of the hypothalamus. Unlike most anterior pituitary hormones, PRL has no apparent target gland which could modulate the endocrine activity of lactotrophs. It is generally agreed that PRL regulates its own release from lactotrophs via the short loop negative feedback mechanism exerted at the level of the hypothalamus or the pituitary. Accordingly, ultrastructural morphology of lactotrophs is not constant; it is changing in response to high PRL levels showing signs of suppressed hormone synthesis and secretion.By transmission electron microscopy and morphometry, we have studied the morphology of lactotrophs in nontumorous (NT) portions of 7 human pituitaries containing PRL-secreting adenoma; these lactotrophs were exposed to abnormally high PRL levels.


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