scholarly journals Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents

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.

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.


1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90


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.


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.


2018 ◽  
Vol 19 (10) ◽  
pp. 3067 ◽  
Author(s):  
Xinli Zhang ◽  
Jin-Kui Yang ◽  
Chen Chen

Significant growth hormone (GH) reductions have been reported in diabetic animal models with disturbed metabolic balance coinciding with GH deficiency. Therefore, enhanced GH secretion may have beneficial effects in controlling diabetes. Thus, we aim to investigate the effect of hexarelin, a synthetic GH secretagogue (GHS), on GH secretion in streptozotocin (STZ, 65 mg/kg)-induced diabetic rats. Daily hexarelin (100 μg/kg) treatment was performed for two weeks in four-week-long STZ-diabetic and vehicle control rats. Pulsatile GH secretion in STZ-rats was significantly reduced in total, pulsatile, basal, and mass of GH secretion per burst. In addition, impaired GH secretion was followed by an increase in fasting-level free fatty acids (FFAs) and a decrease in insulin-like growth factor 1 (IGF-1) compared to control rats. After hexarelin treatment, pulsatile GH secretion in STZ-rats was significantly increased in total, pulsatile, and basal, but not in the mass GH secretion per burst, compared to STZ-rats without hexarelin treatment. However, there was no significant elevation in GH secretion in the hexarelin-treated control group. In addition, hexarelin-treated STZ-rats showed a significant decrease in fasting level FFAs, whereas suppression of fasting level for IGF-1 was maintained. These results suggest that STZ-induced diabetic rats have impaired pulsatile GH secretion, causing increased FFAs and decreased IGF-1 levels in circulation. Hexarelin injections for two weeks is able to normalize impaired pulsatile GH secretion with normal fasting levels of FFAs, but fails to recover IGF-1 levels.


1985 ◽  
Vol 110 (2) ◽  
pp. 152-157 ◽  
Author(s):  
David A. Lewis ◽  
Barry M. Sherman

Abstract. Controversy still exists regarding the role of serotonin in the regulation of prolactin (Prl) and growth hormone (GH) secretion in man. We gave healthy male volunteers three oral doses (0.5, 1.0 and 1.5 mg/kg) of fenfluramine, a serotonin-releasing agent and uptake inhibitor, and a corresponding placebo. There was a significant dose-response effect of fenfluramine on Prl but not on GH levels. Following the highest dose of fenfluramine, mean Prl levels increased from 9.7 ng/ml to 42.3 ng/ml. In a separate study, subjects were pre-treated with cyproheptadine, a serotonin antagonist, before the administration of fenfluramine. Cyprohaptadine did not significantly affect basal Prl or GH levels, but it did blunt the response of Prl to fenfluramine. Cyproheptadine pretreatment did not alter plasma levels of fenfluramine. Our findings support a stimulatory role for serotonin in the regulation of Prl secretion in man. They also suggest that serotonin does not have a major influence on GH secretion in man.


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


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.


Sign in / Sign up

Export Citation Format

Share Document