Increased Serum Growth Hormone Research Articles

Increased serum growth hormone and somatic growth in exercising adult hamsters.

In freely feeding adult hamsters, voluntary exercise induces accelerated somatic growth and increased food consumption that last through several days of retirement. We examined the effects of exercise on serum concentrations of growth hormone (GH) and insulin during ad libitum or restricted intake of food. Serum insulin and GH concentrations were measured by radioimmunoassays in exercising, retired, or sedentary hamsters during ad libitum or restricted intake of food. Linear growth was delayed in food-restricted, exercising hamsters until they were retired and unlimited food consumption was allowed. Serum GH concentrations were increased during exercise and after retirement; serum insulin concentrations were increased only after retirement during both dietary regimes. In food-restricted hamsters, endocrine changes were noted after 4 h of feeding but not after a 14-h fast. We conclude that 1) in adult hamsters voluntary exercise leads to increased secretion of GH even when ingested nutrients are insufficient to support increased growth, and 2) increased secretion of insulin is not related directly to exercise.

A heterologous radioimmunoassay method for measurement of hamster growth hormone.

A heterologous radioimmunoassay (RIA) for determination of hamster growth hormone (GH) is described which involves the use of radioiodinated rat GH (NIAMDD Rat GH-I-2), antiserum to rat GH (NIAMDD Anti-Rat-GHS-3), a standard hamster anterior pituitary homogenate (SHAP), as well as purified hamster GH (AFP-1595-B). This RIA was shown to be a reliable, sensitive, and specific method for measurement of hamster GH. With this method we have determined the effects of stress and hypophysectomy on serum GH concentrations as well as changes in serum GH concentration, and pituitary GH content and concentration as a function of hamster age. In contrast to responses noted in rats, the stress of ether anesthesia and i.c. puncture caused significant increases in serum GH. A decrease in the serum GH concentration was observed in hamsters at the age 2 to 16 days. Pituitary GH content and concentration increased steadily between 9 and 120 days of age.

Clonidine-induced increase in serum growth hormone: Possible role of epinephrine-mediated synapses

(1) The central “alpha adrenergic” agonist and antagonist clonidine (10 μg/kg) and piperoxane (1.0 and 2.5 mg/kg) were administered to nonhuman primates ( M. arctoides) in doses believed to increase or decrease activity at epinephrine-mediated synapses. (2) Clonidine, but not piperoxane or saline, produced a significant ( p < 0.05) rise in serum growth hormone (GH) levels at 30 min after the infusion. (3) Either pre-clonidine or post-clonidine administration of piperoxane blocked the clonidine-induced rise in GH levels. (4) These data support the hypothesis that the clonidine-induced increase in serum GH is mediated by alpha adrenergic receptors and suggest a role for epinephrine-mediated synapses in the stimulation of GH secretion.

Inhibition of dopamine-induced release of growth hormone by thyrotropin-releasing hormone.

The effects of thyrotropin-releasing hormone (TRH) and dopamine (DA) on serum growth hormone (GH) levels were examined in the adolescent male baboon. Intravenously administered DA (40 microgram/kg-min-1 for 20 min) raised serum GH and glucose and lowered serum insulin concentrations but caused no increase in blood pressure. Concomitant intravenous infusion of TRH at 2 doses (96 ng/kg-min-1 and 40 microgram/kg-min-1 for 20 min) blocked the DA-induced increase in serum GH. The relatively low effective doses of TRH used to suppress the DA-induced GH increase suggest an interaction with catecholamines at the hypothalamic and/or pituitary to influence GH release.

Growth Hormone Antiserum Suppresses the Growth Effect of Diabetic Serum: Studies on Rabbit Aortic Medial Cell Cultures

Growth medium containing serum from young diabetic subjects caused a significant stimulation both of cell proliferation and of the outgrowth in cultures of rabbit aortic medial cells above that noted with normal human sera. The addition to the sera of guinea-pig human growth hormones antibody caused a marked inhibition of these stimulatory effects. The growth effect of rabbit serum was not affected by the human growth hormone antiserum. Reinvestigation of the effect of human growth hormone disclosed that the same increase as observed in growth with the diabetic sera could be obtained with a growth hormone concentration of 0.2 ng. per milliliter medium. The present results strongly suggest that the increased stimulatory effect of normolipemic human diabetic serum on growth and cell proliferation of aortic medial cell cultures is due to increased serum growth hormone concentration.

Effect of methysergide and pimozide on apomorphine-induced growth hormone secretion in men.

The dopamine receptor agonist, apomorphine HCl (0.75 mg sc) increased serum growth hormone (GH) concentrations in each of 6 subjects. This increase was not inhibited by pretreatment with the serotonin antagonist, methysergide, but was completely abolished in the 4 individuals pretreated with pimozide, a selective dopamine receptor blocking agent. These results provide further evidence that apomorphine-induced GH secretion is mediated by a dopaminergic mechanism and is independent of a serotonergic mechanism.

Transitory growth hormone deficiency successfully treated with human growth hormone.

This study was carried out in order to determine whether children with a transitory type of growth hormone deficiency showed an accelerated growth in height velocity on treatment with human growth hormone (HGH). Following careful diagnostic routine procedures 13 extremely short children were diagnosed as having isolated growth hormone deficiency, and were successfully treated with HGH. A true isolated growth hormone deficiency was present in 5 of the children, whereas 8 showed a normal increase in serum growth hormone on repeated growth hormone stimulation tests after their development of puberty and termination of HGH treatment. Three boys with bone ages of 5.5, 8.0 and 9.5 years showed an undisputable effect following HGH administration. They showed an initial growth at the start of treatment, and a second growth spurt during development of puberty. Two of the boys reached final statures of 14 cm taller than the predicted heights. The other patients, including the children with true isolated growth hormone deficiency showed an initial spurt of growth at the start of the HGH treatment immediately followed by a pubertal growth spurt. The mean accleration of height velocity for the children with true isolated growth hormone deficiency was from 3.4 cm during the year before treatment to 7.0 cm during the first year on treatment, as compared to 2.8 and 7.4 cm, respectively, for the children with transitory growth hormone deficiency. A girl with severe anorexia nervosa who had a transitory growth hormone deficiency, showed an accelerated high velocity from 1.1 cm to 7.6 cm during the first year following treatment with HGH.

Effect of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy.

Serum growth hormone (GH) and prolactin (PRL) concentrations were measured after administration of the dopamine receptor agonist, apomorphine HC1 (0.75 mg subcutaneously), to 17 chronic schizophrenic patients, four of whom had an oral dyskinesia, who were withdrawn from chronic neuroleptic therapy for periods of two to 15 weeks, and in 21 control subjects (normal volunteers or physically healthy alcoholics not exposed to neuroleptics). Six of the schizophrenic patients, but none of the controls, had raised baseline levels of GH (greater than 6 ng/ml). After apomorphine all controls showed an increase in serum GH with a peak concentration of 9 ng/ml or more, whereas eight subjects withdrawn from neuroleptics showed an inadequate response (peak less than 6 ng/ml) and in two others an inadequate response was obtained on one of two trials. The peak GH concentration was significantly less after apomorphine in patients withdrawn from neuroleptics (11.90 +/- 3.19 ng/ml) compared with controls (20.80 +/- 2.11 ng/ml) (P less than 0.05). Among patients withdrawn from neuroleptics, those with an oral dyskinesia had significantly lower peak GH concentration 2.46 +/- 0.93 ng/ml) after apomorphine compared with those without (14.85 +/- 3.83 ng/ml) (P less than 0.05). There were no differences in serum PRL concentrations, before or after apomorphine administration, between patients withdrawn from neuroleptics and controls. In uncontrolled observations none of the four patients with an oral dyskinesia showed any worsening of the movement disorder after apomorphine. These data provide no evidence for supersensitivity of dopamine receptors in chronic schizophrenic patients withdrawn from chronic neuroleptic therapy.

Effect of Clonidine on Growth Hormone, Prolactin, Luteinizing Hormone, Follicle-Stimulating Hormone, and Thyroid-Stimulating Hormone in the Serum of Normal Men

Clonidine (0.15 mg iv), a selective noradrenergic receptor agonist, increased serum growth hormone (GH) levels (greater than 6 ng/ml) on 8 out of 12 administrations to 6 normal men. This increase was independent of the hypotensive effects of the drug and unrelated to changes in serum cortisol. Clonidine induced a hyperglycemic effect in all subjects which was greatest 15 min after commencint the injection. No changes in blood sugar or GH occurred after placebo injection. Apomorphine, a selective dopamine receptor agonist, elevated GH in each of these 6 subjects (greater than 10 ng/ml). Clonidine had no effect on serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), or thyroid-stimulating hormone (TSH). These data are compatible with a dual dopaminergic and noradrenergic mechanism modulating GH secretion in normal men and with the absence of a noradrenergic mechanism in the regulation of PRL, LH, FSH, or TSH.

Milking, thyrotropin-releasing hormone and prostaglandin induced release of prolactin and growth hormone in cows.

Within 30 min of starting continuous ivy infusion of 333 mug thyrotropin-releasing hormone (TRH)/hr into 12 cows, serum prolactin (PRL) increased more than 10-fold and growth hormone (GH) increased 2.6- to 4-fold above basal concentrations. Constant infusions of 30 mg/hr of prostaglandin F2alpha (PGF2alpha) increased serum PRL and GH to maxima wius infusion of TRH or PGF2alpha, PRL declined throughout the 6- to 13-hr infusion interval although it remained well above preinfusion or saline-infusion control values. Serum GH declined more rapidly than PRL in the face of TRH or PGF2alpha infusions, reaching basal concentrations in one experiment within 1-3 hr. Application of milking stimuli during the 5th hr of TRH infusion caused an additional increase of 23 ng/ml of PRL above the TRH-stimulated concentrations. Similarly, intravenous injection of 5 mg PGF2alpha during the 5th or 12th hr of TRH infusion increased serum PRL an additional 582-682 ng/ml and further increased serum GH 9-91 NG/ML. When 200 mug TRH was injected during the 5th hr of a PGF2alpha infusion, serum PRL increased another 267 ng/ml and GH increased an additional 61 ng/ml. Administration of 10 doses of TRH of 200 mug each in 2 hr did not increase PRL or GH in the serum above that observed when 2.2 mg TRH was infused over a 6-hr period. Collectively, the data suggest that a ceiling exists in cows for secretion of PRL and GH, but this ceiling may be overcome with application of a second heterologous stimulus.

Suppression of serum growth hormone levels by glucagon in patients with active acromegaly.

One mg of glucagon was given subcutaneously to eight patients with active acromegaly. Seven out of eight patients had a rapid decrease in serum growth hormone (GH) levels at 30 min after the glucagon injection. In two out of seven patients a rebound increase in serum GH following the early GH reduction was observed. On the other hand, oral administration of 50 g glucose which caused a comparable increase in blood glucose to that after the glucagon injection elicited no early suppression in serum GH levels in the same patients. These data suggest that the inhibition of GH release induced by glucagon could not be related to the increase in blood glucose by glucagon.

Lack of growth hormone-releasing activity of (pyro)Glu-Ser-Gly-NH 2

Youdaev et al. (1) reported that (pyro)Glu-Ser-Gly-NH 2 isolated from bovine hypothalami or made synthetically stimulates the release of growth hormone (GH). Therefore, we synthesized the tripeptide and tested it in several in vivo and in vitro assay systems for GH releasing activity. Our results demonstrate that (pyro)Glu-Ser-Gly-NH 2 does not stimulate the release of immunoreactive GH from rat pituitaries in vitro in doses of 0.1–1000 nanog/ml. Similarly, (pyro)Glu-Ser-Gly-NH 2, injected intravenously into rats in doses of 1μg and 10μg/rat or infused into a hypophysial portal vessel in doses of 0.01 μg and 0.1 μg/rat did not increase serum GH levels as measured by radioimmunoassay. When this tripeptide was injected intravenously in doses of 500 μg into sheep it did not raise plasma GH levels. These results demonstrate that under the conditions of this investigation (pyro)Glu-Ser-Gly-NH 2 does not display any GH-releasing activity.

Pituitary function in the deprivation syndrome

Fasting serum growth hormone values of infants and some children with thedeprivation syndrome were increased, providing tests were done before unrestricted feeding. Pituitary growth hormone and adrenocorticotropic hormone release were unresponsive to hypoglycemia only in children (5/7); however, some (3/5) had normal or increased serum growth hormone values on admission, and all had normal metyrapone tests. One severely emaciated child probably had deficient growth hormone and thyroid function. Control infants with growth failure due to undernutrition with an organic basis had elevated fasting serum growth hormone values. Insensitivity to hypoglycemia was not related to the severity of the linear growth failure and probably does not reflect growth hormone deficiency at the target organ.

Growth Hormone, Insulin, and Glucose in Suckling, Weanling, and Mature Ruminants

Experiments were designed to test growth hormone and immunoreactive insulin responses of goats and sheep at three stages of development to known stimulators of growth hormone release. Glucose, deoxyglucose, insulin, and arginine were injected intravenously into ruminants in which glucose utilization rates differed, and immunoreactive growth hormone and insulin, and glucose were measured in serum. Increased blood glucose was followed by increased serum growth hormone. Deoxyglucose injections increased glucose but decreased glucose utilization and increased growth hormone (most in suckling and least in mature ruminants). Insulin injections caused the most severe hypoglycemia in weanling ruminants, but there was no age-related difference in the growth hormone response as has been reported for humans. Arginine injections increased growth hormone and insulin in all groups although increases were least in the youngest animals. When compared with the pattern of responses previously reported, especially in mature primates, growth hormone responses to similar stimuli in mature ruminants were more sluggish and the peaks attained were lower. In ruminants intravenous glucose is a potent growth hormone stimulus whereas in primates it is a depressant.

ABNORMAL BLOOD GLUCOSE REGULATION IN COCKAYNE'S SYNDROME

Review of all previous reports of Cockayne's syndrome indicates that the disorder is a unique entity readily identified by certain physical findings and radiographic features. A 16-year-old Negro female with the disorder was found to have hyperglycemia and elevated plasma insulin. Increased serum growth hormone levels were not demonstrated.

UDP-glucose-glucan glucosyl-transferase activity of polymorphonuclear leukocytes from diabetic subjects.

1. In normal leucocytes, glycogen-transferase was only found in the glucose-6-phosphate dependent D-form. An increase in activity was observed within 30 min after glucose feeding, and is assumed to be mediated through the action of released insulin. A late secondary increase in activity occurred simultaneously with an increase in serum growth hormone. — 2. In most diabetic leucocytes, glycogen-transferase was found in both the I- (independent of glucose-6-phosphate) and D-form. The I+D activity was low in uncontrolled diabetes and increased in response to insulin treatment. The I-activity was low immediately upon isolation of the leucocytes, but increased during incubation of the enzyme, especially in the presence of Mg2+; indicating that diabetic leucocytes possess transferase-D phosphatase activity in contrast to normal cells. The D to I transformation of the enzyme was greatly increased by insulin treatment. — 3. K m for UDPG and K a for glucose-6-phosphate did not vary between normal and diabetic leucocytes. — 4. The D to I interconversion of the incubated enzyme from diabetic cells was found to depend on the concentration of ATP and ADP in the incubation medium. It is suggested, that the activating effect of Mg2+ on the D to I transformation is due to an activation of an endogenous ATP-ase and adenylate kinase.

Iatrogenic hypopituitarism in craniopharyngioma: Unexplained catch-up growth in three children

Nine consecutive children with craniopharyngiomas were studied who had relatively normal pituitary function prior to operation. Surgical attempts to remove the craniopharyngiomas were frequently followed by a loss of thyroid stimulating hormone, evaluated indirectly by the butanol extractable iodine, and by failure of adrenocorticotrophic hormone as reflected by a fall in urinary 17-hydroxycorticosteroids and a loss of previously normal SU-4885 responsiveness. In addition, diabetes insipidus, which had not been present preoperatively, invariably followed stalk section which was often necessary during surgery. Despite the postoperative appearance of diabetes insipidus and of thyroid-stimulating hormone and adrenocorticotropic hormone failure, three of ten patients showed “catch-up growth” postoperatively. One of the three had a growth spurt which carried him from below the third up to the fiftieth percentile in 1 1/2 years after operation. He showed no increase in serum growth hormone during arginine or insulin provocative tests. The growth spurts in these three patients are difficult to explain in view of the loss of integrity of their hypothalamic-pituitary pathways.