Glucocorticoid modulation of growth hormone secretion in vitro. Evidence for a biphasic effect on GH-releasing hormone mediated release

Abstract. Glucocorticoids have been shown to have both stimulatory and suppressive effects on GH secretion in vitro and in vivo. In order to study the kinetics of glucocorticoid action on the somatotrope, cultured rat pituitary cells were exposed to dexamethasone for varying periods of time. During short-term incubations (≤ 4 h), dexamethasone inhibited GHRH and forskolin-elicited GH secretion, but during longer incubation periods, the glucocorticoid enhanced both basal and GHRH-stimulated GH release. The inhibitory effect of brief dexamethasone exposure was also seen in cells which previously had been exposed to dexamethasone. In addition, growth hormone secretion from cultured rat and human somatotropinoma cells was inhibited by a brief exposure to dexamethasone. Thus, the nature of glucocorticoid action on the isolated cultured somatotrope is biphasic, with brief exposure inhibiting, and more prolonged exposure stimulating GH secretion.

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Dichotomic action of glucocorticoids on growth hormone secretion

Acta Endocrinologica ◽

10.1530/acta.0.1160165 ◽

1987 ◽

Vol 116 (2) ◽

pp. 165-171 ◽

Cited By ~ 48

Author(s):

Koji Nakagawa ◽

Tatsuya Ishizuka ◽

Takao Obara ◽

Miyao Matsubara ◽

Kazumasa Akikawa

Keyword(s):

Hormone Secretion ◽

Growth Hormone Secretion ◽

Inhibitory Effect ◽

Female Rats ◽

Pituitary Cells ◽

Gh Secretion ◽

Normal Rat ◽

Rat Pituitary Cells

Abstract. The mechanism of apparently discrepant actions of glucocorticoids (GC) on GH secretion, in vivo suppression and in vitro potentiation, was studied in rats. Dexamethasone (Dex), at the concentration of 50 nmol/l, Potentiated basal and GHRH-stimulated GH release from monolayer culture of normal rat pituitary cells in 48 h. On the other hand, in vivo administration of Dex, 165 μg daily for 3 days, consistently suppressed serum GH levels in female rats. In these rats, the hypothalamic content of immunoreactive (IR) SRIH was significantly increased, whereas that of IR-GHRH was significantly decreased in comparison with the untreated rats. Bioassayable GH-releasing activity was also lower in Dex-treated rats. These findings indicate that the suppressing effect of GC on GH release in vivo is, at least partially, due to the increase in hypothalamic SRIH release and probably also to the decrease in GHRH release, and these effects surpass the potentiating effect of GC on GH release at the pituitary level, resulting in a net inhibitory effect in vivo.

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EFFECT OF CHICKEN HYPOTHALAMUS ON PROLACTIN AND GROWTH HORMONE SECRETION IN MALE CHICKENS

Journal of Endocrinology ◽

10.1677/joe.0.0820193 ◽

1979 ◽

Vol 82 (2) ◽

pp. 193-197 ◽

Cited By ~ 18

Author(s):

S. HARVEY ◽

C. G. SCANES ◽

A. CHADWICK ◽

G. BORDER ◽

N. J. BOLTON

Keyword(s):

Growth Hormone ◽

Medulla Oblongata ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Pituitary Cells ◽

Plasma Prolactin ◽

Gh Secretion ◽

Brain Tissues

SUMMARY The effects of a chicken hypothalamic extract (HE) on the secretion of prolactin and growth hormone (GH) in vivo have been investigated by radioimmunoassay in the domestic fowl. Different i.v. doses of HE (0·25–25 HE equivalents/kg body weight) had no effect on GH secretion in conscious or anaesthetized cockerels. In both groups of birds the concentration of plasma prolactin was significantly increased within 10 min of administration of the extract. Extracts of other brain tissues (cerebral cortex, cerebellum and medulla oblongata) had no stimulatory effect on prolactin or GH secretion. Release of both prolactin and GH by dispersed pituitary cells and by hemipituitary glands in vitro was enhanced following incubation with HE (5 hypothalami equivalents/ml) or with single whole hypothalami respectively. Other brain tissues (cerebellum, optic lobes and medulla oblongata) had no effect on the concentration of prolactin or GH released by incubated hemipituitary glands.

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Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents

Endocrinology ◽

10.1210/en.2006-1231 ◽

2007 ◽

Vol 148 (4) ◽

pp. 1648-1653 ◽

Cited By ~ 125

Author(s):

Philippe Zizzari ◽

Romaine Longchamps ◽

Jacques Epelbaum ◽

Marie Thérèse Bluet-Pajot

Keyword(s):

Food Intake ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Male Rats ◽

Pituitary Cells ◽

Gh Secretion ◽

Freely Moving ◽

Stimulation Of

Administration of ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHSR 1a), induces potent stimulating effects on GH secretion and food intake. However, more than 7 yr after its discovery, the role of endogenous ghrelin remains elusive. Recently, a second peptide, obestatin, also generated from proteolytic cleavage of preproghrelin has been identified. This peptide inhibits food intake and gastrointestinal motility but does not modify in vitro GH release from pituitary cells. In this study, we have reinvestigated obestatin functions by measuring plasma ghrelin and obestatin levels in a period of spontaneous feeding in ad libitum-fed and 24-h fasted mice. Whereas fasting resulted in elevated ghrelin levels, obestatin levels were significantly reduced. Exogenous obestatin per se did not modify food intake in fasted and fed mice. However, it inhibited ghrelin orexigenic effect that were evident in fed mice only. The effects of obestatin on GH secretion were monitored in superfused pituitary explants and in freely moving rats. Obestatin was only effective in vivo to inhibit ghrelin stimulation of GH levels. Finally, the relationship between octanoylated ghrelin, obestatin, and GH secretions was evaluated by iterative blood sampling every 20 min during 6 h in freely moving adult male rats. The half-life of exogenous obestatin (10 μg iv) in plasma was about 22 min. Plasma obestatin levels exhibited an ultradian pulsatility with a frequency slightly lower than octanoylated ghrelin and GH. Ghrelin and obestatin levels were not strictly correlated. In conclusion, these results show that obestatin, like ghrelin, is secreted in a pulsatile manner and that in some conditions; obestatin can modulate exogenous ghrelin action. It remains to be determined whether obestatin modulates endogenous ghrelin actions.

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A possible relationship between serum transferrin, growth hormone secretion and height velocity in children

Acta Endocrinologica ◽

10.1530/acta.0.0930134 ◽

1980 ◽

Vol 93 (2) ◽

pp. 134-138 ◽

Cited By ~ 4

Author(s):

M. Donnadieu ◽

R. M. Schimpff ◽

P. Garnier ◽

J. L. Chaussain ◽

J. C. Job

Keyword(s):

Growth Hormone ◽

Growth Regulation ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Height Velocity ◽

Obese Children ◽

Gh Secretion ◽

Growth Promoting

Abstract. Since transferrin (Tf) in vitro has a growth-promoting activity and is associated with NSILA properties, the aim of this work was to study in vivo the relationships between Tf, somatomedin activity (SM), growth hormone (GH) secretion, and height velocity in children. An iv infusion of ornithine hydrochloride was given to 23 controls; the induced rise of GH was accompanied by a simultaneous fall of SM (r = −0.711, P < 0.001) and was preceded by a fall of Tf (r = −0.610, P < 0.01). In 17 obese children SM was within the normal range, when Tf levels were higher and arginineinduced GH peaks lower than in the controls, and a negative correlation was found between Tf basal levels and GH peaks (r = −0.608, P < 0.01). In 9 children with confirmed hypopituitarism the Tf levels were significantly lower than in the controls. In 14 children with confirmed or suspected hypopituitarism a single im injection of hGH (6 mg) failed to induce Tf variations over 24 h. In 39 of these children the height velocity was significantly correlated with Tf basal levels (r = 0.701, P < 0.001). These data suggest that transferrin is involved in growth regulation, and that GH secretion is related to transferrin levels by a feed-back mechanism.

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Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours

Acta Endocrinologica ◽

10.1530/acta.0.1150149 ◽

1987 ◽

Vol 115 (1) ◽

pp. 149-154 ◽

Cited By ~ 23

Author(s):

Eric F. Adams ◽

Maria S. Venetikou ◽

Christine A. Woods ◽

S. Lacoumenta ◽

J. M. Burrin

Keyword(s):

Growth Hormone ◽

Neuropeptide Y ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Inhibitory Effect ◽

Pituitary Cells ◽

Maximal Effect ◽

Human Pituitary ◽

Amino Acid Peptide ◽

Gh Secretion

Abstract. Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25–25 nmol/l) inhibited GH secretion by 20–53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.

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On the role of the peptide galanin in regulation of growth hormone secretion

Acta Endocrinologica ◽

10.1530/acta.0.1250518 ◽

1991 ◽

Vol 125 (5) ◽

pp. 518-525 ◽

Cited By ~ 33

Author(s):

Anna-Lena Hulting ◽

Björn Meister ◽

Lena Carlsson ◽

Agneta Hilding ◽

Olle Isaksson

Keyword(s):

Growth Hormone ◽

Anterior Pituitary ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Pituitary Cells ◽

Anterior Pituitary Cells ◽

Human Anterior Pituitary ◽

Plasma Gh

Abstract. The effects of the peptide galanin on growth hormone secretion were studied in vitro using cultured rat and human anterior pituitary cells, and in vivo by iv administration of galanin in both rats and humans. Galanin in concentrations from 10 nmol/l to 1 μmol/l did not alter basal GH release, but slightly inhibited GHRH-stimulated GH release from cultured rat anterior pituitary cells. Galanin (1 μmol/l) did not significantly change basal or GHRH-stimulated GH secretion from cultured human anterior pituitary cells. In contrast, iv injection of 1 μg (300 pmol) galanin to rats induced an increase in plasma GH that was reproducible at repetitive injections. The galanin-induced GH release in rats was of a lower magnitude than the increase in plasma GH after iv injections of GHRH, and was seen with a 5-15 min delay in comparison to iv administered GHRH. In man, iv infusions of galanin (40 pmol ·kg−1 · min−1 · (40 min)) also caused a significant increase in plasma GH, but it occurred 25-30 min after the beginning of the infusion. These results suggest an indirect action of galanin on GH release in both rats and humans, i.e. galanin does not directly affect the somatotropes. In agreement with a central action, no binding sites for galanin could be demonstrated in the rat anterior pituitary by autoradiography. Since galanin did not affect somatostatin release from fragments of rat mediobasal hypothalamus, the stimulatory effects of galanin on GH release are most likely mediated via a stimulatory effect on GHRH neurons.

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Inhibition of growth hormone secretion by activin A in human growth hormone-secreting tumour cells

Acta Endocrinologica ◽

10.1530/acta.0.1240666 ◽

1991 ◽

Vol 124 (6) ◽

pp. 666-671 ◽

Cited By ~ 5

Author(s):

Masafumi Kitaoka ◽

Kohji Takano ◽

Yuji Tanaka ◽

Itaru Kojima ◽

Akira Teramoto ◽

...

Keyword(s):

Growth Hormone ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Human Growth ◽

Activin A ◽

Tumour Cells ◽

Free Calcium ◽

Gh Secretion

Abstract. Effect of activin A on growth hormone secretion was studied in primary culture of 8 human GH-secreting adenomas, which were responsive to TRH in vivo. When studied in vitro, basal GH secretion was reduced in all cases when cells were pre-incubated for 48 h with activin A at a concentration of 5×10−9 mol/l or greater. Pretreatment of GH-secreting cells with 1× 10−9 mol/l activin A did not affect either basal secretion or cellular content of GH. These tumour cells also responded to TRH in vitro and the GH response to TRH was completely blocked in cells pretreated with activin A. Activin A slightly reduced the increase in cytoplasmic free calcium concentration induced by TRH. Furthermore, pretreatment of the cells with activin A attenuated GH secretion induced by A23187 or 12-O-tetradecanoyl phorbol-4-acetate, agents which bypass receptor-mediated generation of second messengers. These results indicate that activin A inhibits GH secretion by directly acting on human GH-secreting cells and that activin A inhibits the action of TRH by acting on multiple steps in the messenger system.

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Ghrelin-induced growth hormone secretion in humans

Acta Endocrinologica ◽

10.1530/eje.0.143r011 ◽

2000 ◽

pp. R11-R14 ◽

Cited By ~ 162

Author(s):

R Peino ◽

R Baldelli ◽

J Rodriguez-Garcia ◽

S Rodriguez-Segade ◽

M Kojima ◽

...

Keyword(s):

Growth Hormone ◽

Total Dose ◽

Dose Response ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Prolactin Secretion ◽

Gh Secretion ◽

Relevant Dose

Ghrelin is a novel growth hormone (GH) releaser acylated peptide that has recently been purified from stomach, and which potently binds to the GH secretagogue receptor. Ghrelin releases GH in vitro and in vivo in animal models, however its actions, potency and specificity in humans are unknown. In the present study, 12 healthy subjects were studied: 6 underwent four tests with ghrelin administered i.v. at the dose of 0 (placebo), 0.25, 0.5 and 1 microg/kg which corresponds to 0, 18, 37 and 75 microg total dose. A further 6 volunteers underwent two tests on different days with ghrelin at the dose of 3.3 or 6.6 microg/kg which corresponds to 250 microg and 500 microg total dose. Ghrelin-mediated GH secretion showed a dose-response curve, in which 1 microg/kg was the minimally effective dose in some individuals, but not as a group. On the contrary, the total doses of 250 microg and 500 microg elicited a powerful GH secretion, with a mean peak of 69.8+/-9.2 microg/l and 90.9+/-16.9 microg/l respectively, and areas under the curve of 4435+/-608 and 6125+/-1008 microg/l per 120 min respectively. All of them statistically significant vs placebo and vs the 1 microg/kg dose. Ghrelin administration also elicited a relevant dose-response mediated prolactin secretion suggesting no specificity of its actions. No relevant side effects were observed with ghrelin apart from a hyperhydrosis episode in two individuals tested with the higher ghrelin doses. In conclusion, ghrelin is a potent releaser of GH in normal individuals, with a dose-response pattern of operation. No saturating dose was observed.

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