Rise In Plasma GH Levels Research Articles

Effects of Central Infusion of Ghrelin on Food Intake and Plasma Levels of Growth Hormone, Luteinizing Hormone, Prolactin, and Cortisol Secretion in Sheep

Ghrelin is an endogenous ligand for the GH secretagogue/ghrelin receptor (GHS-R) and stimulates feeding behavior and GH levels in rodents and humans. A preprandial increase in plasma ghrelin levels is seen in sheep on programmed feeding, followed by a postprandial rise in plasma GH levels, but effects on food intake and endocrine function are not defined in this ruminant species. We administered ghrelin to female sheep in various modes and measured effects on voluntary food intake (VFI) and plasma levels of GH, LH, prolactin, and cortisol. Whether administered intracerebroventricularly or iv, ghrelin consistently failed to stimulate VFI. On the other hand, ghrelin invariably increased plasma GH levels and alpha,beta-diaminopropanoic acid-octanoyl3 human ghrelin was more potent than ovine ghrelin. Bolus injection of ghrelin into the third cerebral ventricle reduced plasma LH levels but did not affect levels of prolactin or cortisol. These findings suggested that the preprandial rise in plasma ghrelin that is seen in sheep on programmed feeding does not influence VFI but is likely to be important in the postprandial rise in GH levels. Thus, ghrelin does not appear to be a significant regulator of ingestive behavior in this species of ruminant but acts centrally to indirectly regulate GH and LH secretion.

Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats.

Genetically obese male Zucker rats have an impaired secretion of GH, coupled to hyperinsulinemia, hyperlipidemia and glucose intolerance. The aim of this study was to evaluate whether a chronic treatment with hexarelin, a synthetic enkephalin-derived hexapeptide with a potent GH-releasing activity, might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity in male obese Zucker rats. Furthermore, as decreased GH secretion and insulin resistance are associated with increased cardiovascular risk, we also tested the capacity of hexarelin to prevent postischemic ventricular dysfunction in hearts of male obese Zucker rats. Obese and lean male rats of the Zucker strain were treated with hexarelin (80 microgram/kg, b.i.d., s.c.) or saline (1 ml/kg, b.i.d., s.c.) for 30 days. An acute hexarelin injection (80 microgram, s.c.) at the 28th day of treatment elicited a rise in plasma GH levels in ! lean but not in obese rats (pretreated or not with hexarelin); lean rats chronically treated with hexarelin showed a greater increase in plasma GH as compared with control counterparts. At the end of the experiment, pituitary GH mRNA levels were significantly reduced in obese rats and hexarelin administration failed to increase pituitary GH mRNA and IGF-I concentrations in plasma and heart. Chronic treatment with hexarelin increased insulinemia and blood glucose levels in obese but not in lean rats, left unaltered the high triglyceride levels but significantly decreased plasma cholesterol concentrations in obese rats. Heart preparations from lean and obese Zucker rats treated with saline, subjected to low flow ischemia and reperfusion, showed at reperfusion: a) a low recovery of postischemic left ventricular developed pressure (LVDP), coupled to a substantial increase in coronary perfusion pressure, and b) a marked increase in creatine kinase released in the perfusates. Hexare! lin administration for 30 days counteracted the heart ischemic damage both in lean and obese Zucker rats. In fact, the recovery of LVDP at reperfusion was significantly higher than in controls and the increase in coronary resistance was minimal. Collectively, these data indicate that a 30-day treatment with hexarelin was unable to improve somatotropic function in male obese Zucker rats but was successful in decreasing plasma cholesterol concentrations. Hexarelin exerted a cardioprotective effect in both lean and obese rats. The heart-protective activity afforded by the peptide was divorced from any stimulation of the GH axis and is probably exerted through activation of specific cardiac receptors.

Pharmacological manipulations of alpha-adrenoceptors in the infant rat and effects on growth hormone secretion. Study of the underlying mechanisms of action.

The aim of this study was to evaluate whether in infant rats, as in adult rats, the brain adrenergic mechanisms regulate plasma GH levels and, if so, to determine the contribution of GH-releasing hormone (GHRH) and/or somatostatin (SS) pathways. In 10-day-old rats, activation of alpha 2-adrenoceptors by clonidine (CLO) was effective to stimulate GH release starting from 50 micrograms/kg ip and up to 450 micrograms/kg ip, though no dose-related effect was evident. Conversely, alpha 2-adrenoceptor blockade by yohimbine (YOH, 10 mg/kg, ip) decreased baseline GH levels. Administration of methoxamine (METHOX, 10 micrograms/rat, ip), a alpha 1-adrenoceptor agonist, significantly reduced plasma GH concentrations, while prazosin (5 mg/kg BW, ip), a specific alpha 1-adrenoceptor antagonist, stimulated plasma GH secretion. Administration of an anti-SS serum (SS-ab, 300 microliters, ip) induced a significant rise in plasma GH levels, while administration of an anti-GHRH serum (GHRH-ab, 100 microliters, ip) was associated with a striking fall in GH levels. In rats pretreated with SS-ab, administration of CLO induced a further rise in plasma GH levels. GHRH-ab significantly reduced plasma GH levels, and this effect was not altered by subsequent CLO administration. Administration of SS-ab and YOH resulted in plasma GH levels intermediate between those of rats treated with SS-ab alone or YOH alone, while pretreatment with GHRH-ab induced a lowering of plasma GH greater than when YOH was given alone. in rats pretreated with SS-ab, the GH-lowering effect of METHOX was completely lacking, while GHRH-ab and METHOX induced a lowering of plasma GH similar to that ensuing after METHOX alone or GHRH-ab alone. Administration of prazosin in rats pretreated with SS-ab did not elicit any further rise in plasma GH, while combined administration with GHRH-ab elicited a GH-lowering effect comparable to that elicited by GHRH-ab alone. These data demonstrate that in the infant rat: brain adrenergic mechanisms involved in the neural regulation of GH secretion are operative; different neuropeptide mechanisms mediate the effect of activation or inhibition of alpha 1- and alpha 2-adrenoceptors. In particular, activation of alpha 2-adrenoceptors stimulates GH secretion via endogenous GHRH release, although a mechanism operating to inhibit hypothalamic SS release cannot be excluded; stimulation of alpha 1-adrenoceptors is inhibitory to GH secretion exclusively via an increased release of hypothalamic SS.

Growth hormone releasing activity persists in the deafferented medial-basal hypothalamus of the rat.

The possible role of the neural connections of the medial-basal hypothalamus (MBH) in the maintenance of GH releasing activity of the pituitary stalk median eminence (SME) was investigated. Male rats, subjected to sham-operation and to complete and anterolateral cuts around the MBH were used 7-8 days after surgery. Electrical stimulation of neural structures within the MBH caused an increase of plasma GH in pentobarbitone- as well as in urethane-anaesthetized animals. In sham-operated rats the rise of plasma GH levels was apparent only after completion of 10 min of electrical stimulation, while in animals with complete or anterolateral cuts an increase was already evident during electrical stimulation. The results suggest that depolarization of somatostatin secreting fibres in the median eminence may be responsible for the delay in the rise of GH levels in sham-operated rats, while the increment can be attributed to a GH releasing principle in the hypothalamus. Acidic extracts of the SME of rats with complete or anterolateral cuts stimulated the release of GH by primary cultures of rat anterior pituitary cells. Microinjection of 0.05 SME equivalents of SME extract into the anterior pituitary gland of urethane-anaesthetized rats produced a rise in plasma GH levels within 3 min of injection. These data favour the existence of a GH releasing factor, and suggest that the ventromedial and arcuate hypothalamic nuclei are major sites of production of this releasing hormone.

L-Tryptophan injection enhances pulsatile growth hormone secretion in the rat.

The effect of injecting L-tryptophan or a serotonin receptor agonist [6-Cl-2-[1-piperazinyl]pyrazine ((MK0212)] on pulsatile GH secretion was studied in male rats bearing right atrial cannulae. After injection, blood samples were drawn at 15-min intervals for periods up to 4 h. L-Tryptophan administration (50 or 100 mg/kg, ip) significantly enhanced mean plasma GH levels measured over a 3.5-h period. Injection of another large neutral amino acid, L-valine (100 mg/kg, ip), did not influence plasma GH levels. However, when administered with tryptophan, valine blocked the tryptophan-induced enhancement of GH secretion and blunted the increases in brain tryptophan and serotonin levels that normally accompany tryptophan injection. Injection of MK-212 (2 mg/kg, ip) elicited an immediate rise in plasma GH levels; this effect was completely blocked by pretreatment with metergoline (2 mg/kg, ip), a serotonin receptor antagonist. Taken together, these data support the notion that treatments which increase serotonin receptor stimulation enhance or induce pulsatile GH secretion.

Growth hormone, prolactin and thyrotrophin responses to thyrotrophin-releasing hormone in diabetic patients

Growth hormone (GH), prolactin (PRL) and thyrotrophin (TSH) responses to thyrotrophin-releasing hormone (TRH) were studied in 15 insulin-dependent diabetic patients. Basal plasma GH levels were raised above 5 mu./l in 6 patients and following the injection of TRH there was a significant rise in plasma GH levels in 9. The mean rise in plasma GH from basal to peak values was significant in the group as a whole (P < 0.01). Basal PRL and TSH levels were normal and rose normally in response to TRH. GH release may be qualitatively abnormal in some diabetics and any such loss of specificity of GH-releasing mechanisms would further contribute to the raised GH levels found in many diabetics which would be of importance if GH is a factor in the aetiology of diabetic microangiopathy.

Effects of a dopaminergic stimulant, amfonelic acid, on anterior pituitary hormone release in conscious rats

The response of plasma LH, Prolactin, GH and TSH levels to systematic administration of a specific central dopaminergic stimulant, amfonelic acid (AFA), by intravenous pulse injection in ovariectomized (OVX) and OVX estrogen-progesterone primed conscious rats has been evaluated. Intravenous injection of 0.2 mg/kg of AFA had no influence on plasma LH concentration until 60 min after injection when it was significantly elevated. Increasing the dose to 1 mg/kg reduced LH titers at 15 and 30 min with a return to preinjection levels by 60 min. AFA produced a dose-dependent decrease in plasma prolactin levels; the decrease occurred as early as 5 min after injection. AFA, both at 0.2 and 1 mg/kg doses, was effective in producing a sharp, dose-related rise in plasma GH levels. By contrast, TSH levels were significantly suppressed by both doses of AFA. Injection of the 1 mg/kg dose of AFA did not modify plasma LH levels in OVX-steroid-primed animals, white producing a comparable effect on plasma prolactin, GH and TSH levels to that observed in OVX animals. The present results indicate that endogenously released DA can have profound effects on pituitary hormone release, inhibiting PRL and TSH discharge, stimulating GH release and either inhibiting or stimulating LH release.

Stimulation of growth hormone secretion by median eminence extracts in the sheep.

Extracts of bovine stalk-median eminence fragments (SME) equivalent to 3–5 glands were infused into the carotid artery of young sheep. Plasma GH increased from 4.8 at zero time to 17.7 mμg/ml 30 min after infusion had begun. Infusion of saline or cerebrum extracts had no effect on plasma GH. SME extracts also caused an elevation of plasma glucose and insulin which preceded the rise in GH. Evidence is presented which indicates that the rise in plasma GH levels is not a response to insulin but is a direct effect of a releasing factor in the SME extracts. (Endocrinology 80: 205, 1967)