Growth Hormone Secretion In Sheep Research Articles

Effect of intravenous administration of glucagon-like peptide 1 on growth hormone secretion in sheep

Effect of intravenous administration of glucagon-like peptide 1 on growth hormone secretion in sheep

Insulin hypoglycemia and growth hormone secretion in sheep: a paradox revisited.

Although insulin-induced hypoglycemia is a potent stimulus for growth hormone (GH) secretion in humans, hypoglycemia was reported to suppress GH in sheep. We investigated whether GH suppression in sheep during insulin hypoglycemia resulted from the dose of insulin administered or the fed state of the animal. Saline or insulin (0.05, 0.2, 1.0, or 5.0 U/kg) intravenous boluses were administered to eight fasted ewes in a crossover experiment. In another experiment, four sheep were fed 2 h before intravenous administrations of either 0.2 or 5 U/kg of insulin. All doses of insulin resulted in comparable hypoglycemia, although the duration of hypoglycemia increased directly with insulin dose. Hypoglycemia in fasted animals stimulated GH secretion. The GH rise above baseline was inversely related to the insulin dose, and the insulin doses of 1 and 5 U/kg resulted in late suppression of GH below baseline concentrations. Insulin administration to fed animals caused an identical degree of hypoglycemia but no increase in GH. Insulin-hypoglycemia stimulates GH secretion in sheep in a manner similar to humans, and the response is dependent on both fed state and insulin dose.

Hypothalamic Mediated Action of Free Fatty Acid on Growth Hormone Secretion in Sheep

Hypothalamic Mediated Action of Free Fatty Acid on Growth Hormone Secretion in Sheep

Hypothalamic mediated action of free fatty acid on growth hormone secretion in sheep.

Experimental data suggest that elevated FFA levels play a leading role in the impaired GH secretion in obesity and may therefore contribute to the maintenance of overweight. GH has a direct lipolytic effect on adipose tissue; in turn, FFA elevation markedly reduces GH secretion. This suggests the existence of a classical endocrine feedback loop between FFA and GH secretion. However, the FFA mechanism of action is not yet understood. The involvement of somatostatin (SRIH) is controversial, and in vitro experiments suggest a direct effect of FFA on the pituitary. In sheep it is possible to collect hypophysial portal blood and quantify SRIH secretion in hypophysial portal blood under physiological conscious and unstressed conditions. In this study we determined the effects of FFA (Intralipid and heparin) infusion on peripheral GH and portal SRIH levels in intact rams chronically implanted with perihypophysial cannula and in rams actively immunized against SRIH to further determine SRIH-mediated FFA effects on GH axis. Immediately after initiation of Intralipid infusion, we observed a marked increase in the FFA concentration (2160 +/- 200 vs. 295 +/- 28 nmol/ml; P < 0.01) as well as a significant decrease in basal GH secretion (1.8 +/- 0.1 vs. 2.5 +/- 0.3 ng/ml; P < 0.05) and a drastic reduction of the GH response to i.v. GH-releasing hormone injection (4.8 +/- 0.7 ng/ml in FFA group vs. 35.8 +/- 9.7 ng/ml in saline group; P < 0.01). No change in plasma insulin-like growth factor I levels was observed. During the first 2 h of infusion, the GH decrease observed was concomitant with a significant increase in portal SRIH levels (22.1 +/- .2 vs. 13 +/- 1.6 pg/ml; P < 0.01). In rams actively immunized against SRIH, the effect of FFA on basal GH secretion was biphasic. During the first 90 min of infusion, the decrease in GH induced by FFA was significantly blunted in rams actively immunized against SRIH (57 +/- 9% for immunized rams vs. 23.5 +/- 2.5% for control rams). This corresponds to the period of increased SRIH portal levels. After this first 90-min period, no difference was seen between control and immunized rams. Our results show that FFA exert their inhibitory action on the GH axis at both pituitary and hypothalamic levels, the latter mainly during the first 90 min, through increased SRIH secretion.

Effect of abomasal infusion of alanine and aspartic acid on growth hormone secretion in sheep

Effect of abomasal infusion of alanine and aspartic acid on growth hormone secretion in sheep

Neuroendocrine regulation of growth hormone secretion in sheep. VII. Effects of GABA

The effects of intravenous (i.v.) or intracerebroventricular (i.c.v.) administration of γ aminobutyric acid (GABA) on plasma growth hormone (GH) concentrations have been examined in sheep. Intravenous administration of GABA resulted in a rapid, significant ( P<0.001) increase in plasma GH. Administration of 10 mg of GABA i.c.v. produced a significant ( P<0.001) increase in GH release. By contrast, 100 mg given i.c.v. was inhibitory and resulted in a decrease ( P<0.05) in plasma GH levels. Concurrent administration of somatostatin (0.5 μg/min i.v. over 1 h) did not alter the plasma GH response to 10 mg GABA given i.c.v. These data are consistent with the concept of dual sites of action for GABA in regulating GH release in sheep, but the exact mechanism through which this effect is mediated remains unclear.

Adrenergic regulation of growt hormone secretion in the ewe

This study examined the role of the adrenergic system in the regulation of growth hormone (GH) secretion in sheep. Intravenous infusion of noradrenaline (0.5μg/kg per min for 2 hr) totally suppressed plasma GH concentrations. Concomitant treatment of animals with the β-adrenergic antagonist propranolol completely blocked the noradrenaline-induced suppression of GH. In contrast, intravenous injection of the centrally acting α 2-agonist clonidine (2μg/kg) elicited a release of GH. To further investigate the central adrenergic regulation of GH secretion 10 μg of noradrenaline or adrenaline was microinjected (1μl) directly into the preoptic area of the hypothalamus of ovariectomized ewes. When the time of injection coincided with a GH trough period, both noradrenaline and adrenaline caused an increase in plasma GH concentrations, whereas if the injection coincided with an endogenous pulse of GH no additional GH response was obtained. In conclusion, these results provide evidence for the involvement of the adrenergic system in the regulation of GH secretion in sheep. Centrally, adrenergic pathways exert a stimulatory effect on GH release via an α 2-adrenergic system, whereas peripherally adrenergic pathways exert an inhibitory effect via β-adrenergic mediated mechanisms. Furthermore, adrenergic stimulation of the preoptic area may inhibit somatostatin activity and directly facilitate a GH pulse. Alternatively, adrenergic innervation of the preoptic area may influence neurons (somatostatin or other) that project to the arcuate nucleus and stimulate the release of GH-releasing factor.

Constitutive growth hormone secretion in sheep after hypothalamopituitary disconnection and the direct in vivo pituitary effect of growth hormone releasing peptide 6.

The effect of hypothalamopituitary disconnection (HPD) on growth hormone (GH) secretion was studied in sheep. Plasma GH levels were measured in serial blood samples (10 min x 6-8 h) taken from 12 Romney wethers and 5 ewes which had undergone HPD 40-506 days earlier and from 4 wethers (10 min x 7 h) to serve as controls. Five wethers and 5 ewes were taken approximately 300 days after HPD and injected with vehicle or 10 micrograms/kg of the synthetic hexapeptide growth hormone-releasing peptide 6 (GHRP-6); GH responses were monitored. In a second series of sheep, 4 wethers and 6 HPD wethers were given saline, 0.5 micrograms/kg of synthetic growth hormone-releasing factor (GRF) or 5 micrograms/kg GHRP-6 and were blood-sampled to measure the plasma GH response. A further group of 4 HPD wethers and 3 control wethers were killed and the anterior pituitary glands collected for the quantification of GH and LH beta mRNA by Northern analysis. Three HPD wethers and 1 HPD ewe and 1 control ewe were killed and their brains were perfused; the hypothalami were sectioned and immunostained for the presence of GRF-containing fibres in the median eminence. Normal episodic GH secretion was abolished by HPD in both wethers and ewes but plasma values did not fall below the assay detection limit, indicating constitutive secretion. Northern blot analyses showed that the GH mRNA was detectable in HPD wethers at a lower (p < 0.05) level than in control animals but mRNA for LH beta was undetectable in the HPD wethers. Immunohistochemistry revealed GRF-positive staining in the median eminence of the controls but GRF-positive staining was not seen below the operation site in the median eminence of the HPD animals. In the first series, 3/5 wethers and 3/5 of the ewes responded to GHRP-6 challenge; the magnitude of the response was similar in both sexes. In the second series, responses to GRF were lower (48%) (p < 0.03) in HPD wethers than in control wethers, and responses to GHRP-6 were much lower (p < 0.01) than those to GRF in both controls and HPD wethers. These studies show that HPD removes GRF inputs to the pituitary gland and abolishes pulsatile GH secretion in most cases but constitutive non-pulsatile secretion continues. The HPD wether pituitary glands had lower GH mRNA levels than controls. Accordingly, HPD sheep were able to respond to a single injection of GRF although the response was half that seen in control animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuroendocrine regulation of growth hormone secretion in sheep. V. Growth hormone releasing factor and thyrotrophin releasing hormone

The effects of intravenous (IV) and intracerebroventricular (ICV) administration of either bovine growth hormone releasing hormone (GRF) or thyrotrophin releasing hormone (TRH) on plasma growth hormone (GH) and glucose levels have been examined in sheep. Intravenous GRF 1–29NH 2 at 3 and 30 μg stimulated an increase in GH levels in a dose-dependent fashion; administration of GRF into a lateral cerebral ventricle, however, produced a smaller GH response which was similar at these two doses. Evaluation of somatostatin levels in petrosal sinus blood (which collects pituitary effluent blood) showed that ICV administration of GRF stimulated a release of somatostatin into the blood. Furthermore, concurrent administration of GRF and a potent anti-somatostatin serum ICV resulted in a much enhanced release of GH which was similar to that obtained with a comparable dose of GRF given IV. TRH (as another putative GH-secretagogue) was also administered both IV and ICV. When given IV, 200 μg (but not 100 μg) TRH produced an elevation in GH levels. By contrast, when 5 μg TRH was given ICV there was a decrease in circulating GH levels, but no change in plasma somatostatin concentrations. These results indicate that the smaller GH response to ICV- compared with IV-administered GRF is due to the release of somatostatin within the brain. In addition, it would seem that TRH is not a physiological GH-secretagogue in sheep.

Effects of intracerebroventricular corticotropin-releasing hormone and intravenous morphine on cortisol, prolactin and growth hormone secretion in sheep

It has previously been demonstrated that naloxone and morphine modify the adrenocortical and pituitary responses of sheep to stress. Since CRH acts within the brain to co-ordinate the stress response, the present experiment was conducted to determine whether morphine has similar effects in sheep given oCRH centrally. Plasma concentrations of cortisol, prolactin and growth hormone were measured in blood samples collected at 10 min intervals from sheep (N=5) over a 3-hr period. Intravenous injections of saline vehicle or morphine sulphate (0.4 mg/kg) were given after 40 min and intracerebroventricular injections of oCRH (0, 5 or 20 μg) were administered after 60 min. Sustained, dose-related, increases in cortisol were induced by oCRH and, in agreement with findings in stressed sheep, these responses were reduced by pretreatment with morphine. Prolactin levels appeared to increase after morphine but oCRH, on its own, did not increase prolactin secretion in this study. There was no change in growth hormone concentrations after oCRH whereas morphine transiently stimulated release.

Neuroendocrine regulation of growth hormone secretion in sheep. IV. Central and peripheral cholecystokinin

The result of alterations in the levels of CCK, in the blood and in the cerebrospinal fluid, on the functioning of the growth hormone axis has been examined in sheep. Male Coopworth sheep of about 40 kg liveweight were given various doses of CCK either intracerebroventricularly ( icv) or intravenously ( iv). Other similar sheep were given various doses of a CCK antagonist (loxiglumide) by the same routes. Bolus iv administration of either 35 μg or 200 μg of CCK had no effect on plasma GH levels. When given icv, however, CCK resulted in a marked (P<0.01) prolonged depression in plasma GH levels. The decrease in GH secretion could be partially attenuated by concurrent administration of loxiglumide, but was completely unaffected by concurrent administration of anti-somatostatin serum icv. Loxiglumide alone had no effect on plasma GH levels when given at up to 200 μg icv, but intravenous administration of 8 mg of the CCK antagonist resulted in an increase in plasma GH concentrations (P<0.05). Plasma levels of somatostatin, glucose and cortisol were unaffected by both icv and iv administration of CCK. These results show that CCK can have a strong GH-inhibiting effect in the brain. Furthermore, this effect seems to be independent of hypothalamic somatostatin, suggesting another GH-inhibiting system exists.

Neuroendocrine regulation of growth hormone secretion in sheep III. Serotoninergic systems

The role of serotoninergic pathways in the regulation of growth hormone secretion in the sheep has been investigated. Both peripheral and central routes of administration of serotonin agonists and antagonists have been used. Intravenous administration of the serotonin agonist, buspirone, at 1.2 mg/kg/h lowered plasma GH levels (P<0.001) but at 0.21 mg/kg/h there was no significant decrease. Intracerebroventricular ( icv) administration of serotonin itself also depressed GH levels (P<0.01). The serotonin antagonist, cyproheptadine, failed to affect GH concentrations when given either intravenously (0.25 mg/kg/h) or intracerebroventricularly (4 mg). Neither serotonin nor cyproheptadine had any significant effect on plasma glucose or cortisol levels when administered icv. The possible role of somatostatin in mediating the serotonin associated decrease in GH was investigated by concurrent administration of serotonin and a specific, potent anti-somatostatin serum into a cerebral ventricle. This treatment also resulted in a marked, sustained depression in GH (P<0.001). These data suggest that serotonin can inhibit release of GH from the pituitary in sheep and that this is independent of hypothalamic somatostatin.

Neuroendocrine regulation of growth hormone secretion in sheep II. Effect of somatostatin on growth hormone and glucose levels

The effect of intravenous ( iv) and intracerebroventricular ( icv) administration of somatostatin on the plasma levels of growth hormone (GH) and glucose was studied in sheep. Intravenous somatostatin decreased (P<0.001) circulating GH when infused at the rate of 5 μg/min (150 ng/kg/min) over 1 hr, but when used at 1 μg/min there was no effect on plasma GH levels during infusion. At both doses used there was an indication of an increase in GH following the cessation of somatostatin infusion. Somatostatin given at both these doses iv had no effect on plasma glucose levels. When given icv neither 1.8 μg, 18 μg nor 180 μg somatostatin had any significant effect of plasma GH levels, although there was a significant (P<0.05) elevation in GH levels 75 min after 180 μg somatostatin icv. Plasma glucose levels did not increase following injection of somatostatin icv at 1.8 or 18 μg, but there was a clear hyperglycaemic episode following 180 μg icv. Despite a lack of effect of somatostatin on GH release when given icv, there was a clear elevation (P<0.05) in plasma GH levels immediately following icv administration of a somatostatin antiserum. These data indicate that iv administration of somatostatin at pharmacological levels can depress unstimulated GH levels in sheep while administration icv does not. Central administration of somatostatin increases plasma glucose levels only at high doses and seems unlikely to be of physiological importance in glucose homeostasis.

Episodic growth hormone secretion in sheep in relation to time of feeding, spontaneous meals and short term fasting.

1. Blood samples were taken every 20 min (for at least 28 hr) from five castrate male and two anoestrus female and libitum fed sheep. Analysis for plasma growth hormone (GH) showed that two of the males, on two occasions, had regular, although individually specific, patterns of GH secretion (peaks 3.5-5 hr). The other animals all had irregular patterns of GH release. 2. Throughout the experiments, meal sizes and frequency were recorded and it was found that out of eighty spontaneous meals of at least 50 g, 57 (71%) occurred in the hour after GH peaks, which accounted for 50% of the total time. Furthermore, on twenty out of twenty-four occasions GH levels were found to be falling before the 'expected' feeding time when fresh food was offered and the animals normally consumed a large meal. The removal of the food from three of the males for 10 hr during an experiment prompted an increase both in the size and frequency of the GH peaks. After re-feeding, GH levels immediately fell and remained low for 1-2 hr. 3. We believe that these results show an association between GH secretion and meal feeding in sheep, and that GH secretion quickly responds to fasting. As GH levels fell before, or in the early stages of meals, this indicates a neural reflex in the inhibition of GH before a meal.

Plasma levels of prolactin, growth hormone and insulin in sheep following the infusion of arginine, leucine and phenylalanine.

The effects of amino acid infusions on plasma levels of prolactin (Prl), growth hormone (GH) and insulin (Ins) in sheep were studied using specific double antibody radioimmunoassay systems. The infusion of arginine (0.5 g/kg), leucine (0.2 g/kg) and phenylalanine (0.3 g/kg) into the carotid artery (via an indwelling cannula) of mature, anestrus ewes, resulted in a significant increase in plasma levels of Prl. Arginine and leucine also stimulated significant increases in plasma GH and insulin levels, while the phenylalanine treatment significantly increased plasma levels of insulin but not GH. The intrajugular injection of arginine (0.5 g/kg) into immature male and female sheep also produced significant increases in Prl, GH and insulin. It was also observed that physically or psychologically stressful factors may produce a significant elevation in plasma levels of Prl, but do not appear to affect GH secretion in sheep. (Endocrinology 91: 205, 1972)

Effects of cyclic AMP and epinephrine on insulin and growth hormone secretion in sheep.

Effects of cyclic AMP and epinephrine on insulin and growth hormone secretion in sheep.

Influence of blood glucose levels on growth hormone secretion in sheep.

SummaryConcentrations of plasma GH, as estimated by radioimmunoassay, did not change significantly in sheep during the 72 hr after feeding; however, the concentrations of blood glucose and plasma insulin decreased and levels of plasma FFA increased markedly. Furthermore, insulin-induced hypoglycemia was not a stimulus for GH secretion. Rapidly falling blood glucose levels from normal or hyperglycemic levels stimulated an increase in plasma GH concentration of short duration. Growth hormone disappeared from plasma with a half-life of 8.6 to 14.7 min. Growth hormone was distributed in a volume equal to 5.0% of body weight. The average GH secretion in 40-kg sheep was estimated to be 0.7 μg/kg/hr.