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

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1648-1653 ◽  
Author(s):  
Philippe Zizzari ◽  
Romaine Longchamps ◽  
Jacques Epelbaum ◽  
Marie Thérèse Bluet-Pajot

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.

1987 ◽  
Vol 116 (2) ◽  
pp. 165-171 ◽  
Author(s):  
Koji Nakagawa ◽  
Tatsuya Ishizuka ◽  
Takao Obara ◽  
Miyao Matsubara ◽  
Kazumasa Akikawa

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.


1987 ◽  
Vol 114 (4) ◽  
pp. 465-469 ◽  
Author(s):  
Gian Paolo Ceda ◽  
Robert G. Davis ◽  
Andrew R. Hoffman

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.


1979 ◽  
Vol 82 (2) ◽  
pp. 193-197 ◽  
Author(s):  
S. HARVEY ◽  
C. G. SCANES ◽  
A. CHADWICK ◽  
G. BORDER ◽  
N. J. BOLTON

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.


1980 ◽  
Vol 93 (2) ◽  
pp. 134-138 ◽  
Author(s):  
M. Donnadieu ◽  
R. M. Schimpff ◽  
P. Garnier ◽  
J. L. Chaussain ◽  
J. C. Job

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.


Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 4031-4041 ◽  
Author(s):  
Warren K. Yunker ◽  
Sean Smith ◽  
Chad Graves ◽  
Philip J. Davis ◽  
Surajlal Unniappan ◽  
...  

Abstract Using Southern blot analysis of RT-PCR products, mRNA for three different somatostatin (SS) precursors (PSS-I, -II, and -III), which encode for SS14, goldfish brain (gb)SS28, and [Pro2]SS14, respectively, were detected in goldfish hypothalamus. PSS-I and -II mRNA, but not PSS-III mRNA, were also detected in cultured pituitary cells. We subsequently examined the effects of the mature peptides, SS14, gbSS28, and [Pro2]SS14, on somatotrope signaling and GH secretion. The gbSS28 was more potent than either SS14 or [Pro2]SS14 in reducing basal GH release but was the least effective in reducing basal cellular cAMP. The ability of SS14, [Pro2]SS14, and gbSS28 to attenuate GH responses to GnRH were comparable. However, gbSS28 was less effective than SS14 and [Pro2]SS14 in diminishing dopamine- and pituitary adenylate cyclase-activating polypeptide-stimulated GH release, as well as GH release resulting from the activation of their underlying signaling cascades. In contrast, the actions of a different 28-amino-acid SS, mammalian SS28, were more similar to those of SS14 and [Pro2]SS14. We conclude that, in goldfish, SSs differentially couple to the intracellular cascades regulating GH secretion from pituitary somatotropes. This raises the possibility that such differences may allow for the selective regulation of various aspects of somatotrope function by different SS peptides.


1991 ◽  
Vol 125 (5) ◽  
pp. 518-525 ◽  
Author(s):  
Anna-Lena Hulting ◽  
Björn Meister ◽  
Lena Carlsson ◽  
Agneta Hilding ◽  
Olle Isaksson

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.


1986 ◽  
Vol 108 (3) ◽  
pp. 413-416 ◽  
Author(s):  
C. G. Scanes ◽  
S. Harvey ◽  
J. Rivier ◽  
W. Vale

ABSTRACT Rat hypothalamic GH-releasing factor (rhGRF), at doses between 0·1 and 10 μg/kg, increased plasma GH concentrations in immature domestic fowl 5–10 min after i.v. injection. Sodium pentobarbitone anaesthesia blunted the GH responses to rhGRF, although in both conscious and anaesthetized chicks the maximal responses were induced by a dose of 1 μg rhGRF/kg. The stimulatory effect of rhGRF on in-vivo GH secretion was less than that provoked by corresponding doses of human pancreatic GRF, but greater than that elicited by two rhGRF analogues, (Nle27)-rhGRF(1–32) and (Nle27)-rhGRF(1–29). These results demonstrate that the chicken pituitary is responsive to mammalian GRF and provide evidence of structure-activity relationships of GRF in the domestic fowl. J. Endocr. (1986) 108, 413–416


1987 ◽  
Vol 116 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Maria S. Venetikou ◽  
Jacky M. Burrin ◽  
Christine A. Woods ◽  
Tom H. Yeo ◽  
Judith Brownell ◽  
...  

Abstract. Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.


1993 ◽  
Vol 137 (2) ◽  
pp. 329-334 ◽  
Author(s):  
M. Daniels ◽  
P. E. Harris ◽  
R. A. James ◽  
S. J. Turner ◽  
J. H. Dewar ◽  
...  

ABSTRACT Activin A is a homodimer of inhibin βA subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The βA subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques. Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0·01–10 nmol recombinant human activin A/1 followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12–63% above control values during treatment with 0·01–10 nmol activin A/1, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0·01–1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these. These data demonstrate that activin A stimulates basal GH secretion from the cells of some, but not all, human somatotrophinomas in vitro. Pretreatment with the peptide may also partially block GRF-stimulated GH release from GRF-responsive somatotrophinoma cells. The importance of these actions in the pathophysiological regulation of human somatotrophinomas remains to be determined. Journal of Endocrinology (1993) 137, 329–334


Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Rubén Nogueiras ◽  
Paul Pfluger ◽  
Sulay Tovar ◽  
Myrtha Arnold ◽  
Sharon Mitchell ◽  
...  

Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its biological activity and acts through the orphan receptor, GPR-39. Obestatin was shown to have actions opposite to ghrelin on food intake, BW, and gastric emptying. In the present study, we failed to observe any effect of obestatin on food intake, BW, body composition, energy expenditure, locomotor activity, respiratory quotient, or hypothalamic neuropeptides involved in energy balance regulation. In agreement with the first report, we were unable to find any effect of obestatin on GH secretion in vivo. Moreover, we were unable to find mRNA expression of GPR-39, the putative obestatin receptor, in the hypothalamus of rats. Therefore, the results presented here do not support a role of the obestatin/GPR-39 system in the regulation of energy balance.


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