Direct effect of human growth hormone to inhibit glucose uptake in cultured human fibroblasts

We have examined the effect of human growth hormone (HGH) on both basal and insulin stimulated glucose uptake in human fibroblasts. High concentrations of HGH (100 μg/mL) depressed both basal and insulin-stimulated glucose uptake by 25%. Significant inhibition was not seen at concentrations below 50 μg/mL of HGH. HGH-related hormones like human prolactin and ovine growth hormone had no effect on glucose uptake while high concentrations of ovine prolactin reduced basal glucose uptake, albeit to a lesser degree than HGH. In conclusion, high concentrations of HGH act independently of insulin to inhibit glucose uptake in human fibroblasts. These data may help explain the glucose imbalance and insulin resistance that is characteristic of acromegaly.     

Influence of acute administration of human growth hormone and alpha-MSH on plasma concentrations of aldosterone, cortisol, corticosterone and growth hormone in man.

The effect of acute administration of human growth hormone (HGH) and of alpha-melanocyte stimulating hormone (alpha-MSH) on plasma aldosterone, cortisol, corticosterone and growth hormone has been studied in normal man and in patients with panhypopituitarism. There is no acute effect of exogenous HGH on plasma levels of aldosterone, cortisol and corticosterone in normal man and in patients with panhypopituitarism. The plasma level of immunoreactive HGH measured during acute HGH infusion in man does not seem to be proportional to the dose administred in our study. Alpha-MSH raises the concentartion of plasma HGH, BYT THIS STIMULATION IS NOT DOSE-DEPENDENT. Aldosterone, cortisol and corticosterone concentrations are not influenced by the elevation of HGH mediated by alpha-MSH in normal man. Although in some patients with panhypopituitarism an elevation of plasma aldosterone concenntration following alpha-MSH infusion is observed, it is unlikely that MSH is directly involved in the acute regulation of aldosterone secretion in healthy subjects.     

Human growth hormone as a regulator of blood glucose concentration and as a diabetogenic substance

Summary Human growth hormone (HGH) has recently been shown to play a prominent role in the control of blood glucose homeostasis. Furthermore, it has long been known that administration of growth hormone in animals can induce a diabetes-like state. In human subjects, exogenous administration of HGH or hypersecretion of the endogenous hormone in acromegaly is accompanied by glucose intolerance in only about 25 per cent of the cases. — In this paper, data are presented which give a more diversified picture of the so-called diabetogenic action of HGH. It is suggested that HGH, although decreasing the peripheral utilization of glucose, is not a primary diabetogenic factor, since its insulinogenic action causes a compensatory hyperinsulinism, with normal glucose tolerance as the result. HGH is diabetogenic only in prediabetic subjects whose pancreas is unable to respond to the insulinogenic effect of the hormone. In such subjects, the diabetogenic action of HGH not being counterbalanced by a compensatory hyperinsulinism, glucose intolerance may result. Thus, HGH may be regarded as anadditional factor for the development of diabetes, the major prerequisite being a preëxisting prediabetic state.Presented as an invited lecture at the VI Acta Endocrinologica Congress, Helsinki, Finland, August 8th–12th, 1967.     

Correlative study of radioreceptor assay and radioimmunoassay of serum growth hormone in children: normal children and HGH-treated pituitary dwarfs

A sensitive and reproducible radioreceptor assay (RRA) for human growth hormone (HGH) is described. It allows the evaluation of HGH concentrations as low as 2 ng/ml. It has a limited cross-reactivity with human prolactin, which does not interfere at physiological levels in children. Comparison of the results with those of radioimmunoassay (RIA) showed no discrepancies in the serum of normal children before and after stimulation tests for GH (mean RRA/RIA ratio 1.03 +/- SEM 0.04, range 0.75 to 1.65) nor in the serum from hypopituitary dwarfs during the 12 h following an im injection of 6 mg of HGH (mean RRA/RIA ratio 1.05 +/- 0.04, range 0.84 to 1.28). It is concluded that receptoractivity of HGH is parallel to its immunoreactivity in normal children and in hypopituitary patients clinical grade HGH.     

重组人生长激素在成人生长激素缺乏症的应用

近20年来,重组生长激素已可以无限量的制备。近年来的研究已阐明成人生长激素缺乏的影响及生长激素替代治疗的益处。成人生长激素缺乏症对人影响最大的是生活质量、骨骼健康及包括血清脂质谱、身体构成变化的心血管危险因子的改变,而这也正是生长激素替代治疗获益最显著之处。大量的证据显示了重组人生长激素治疗的疗效,尤其在改善骨代谢和改善心血管危险因素等多方面发挥作用,并且是安全的。     

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.     

Determination of growth hormone in plasma of psoriatic arthritis, psoriasis vulgaris and seronegative spondylarthritis

By means of radio-immunoassay the concentration of human growth hormone (HGH) was measured in the blood plasma of 61 patients with psoriasis (21 suffering from psoriasis vulgaris and 40 with psoriatic arthritis), 30 patients with ankylosing spondylitis, 9 with atypical spondylarthritis and 34 patients with diseases of the soft tissue or degenerative joint and spinal column disease. No connection was found between the HGH concentration and the skin lesions in psoriasis. On the other hand a correlation between HGH and the sacroiliitis in psoriatic arthritis and seronegative spondyloarthropathies may be possible. In contrast to the plasma of psoriatics, the mean HGH concentration was higher in the plasma of patients with degenerative joint diseases. Therefore the results of this paper confirm those opinions in the literature which deny increased HGH concentrations in psoriatics. The beneficial effect of the therapeutic administration of somatostatin, an inhibitor of the release of HGH, in psoriasis vulgaris and psoriatic arthritis is - if indeed it occurs - attributable to other hitherto unidentified mechanisms.     

Biphasic action of human growth hormones, of hypophyseal origin or bacterial production, on the lipolysis of rat adipocytes in vitro

Actions of: human growth hormone resultant from hypophysis: HGH h (contaminated by beta LPH 1%) or produced by bacteria HGH b (pure), beta LPH resultant from human hypophysis, one of the somatomedins: multiplication stimulating activity (MSA), produced from a culture of rat hepatocytes, are considered in lipolysis of rat adipocytes "in vitro": basal, stimulated by epinephrine (0.1 and 1 microgram/ml), and when insulin is present (0.1 and 1 mUI/ml), during two periods I: 0-1 h 30, II: 1 h 30 - 4 h (hormonal addition at time 0). MSA appears to be antilipolytic during the two periods, between 0 and 4 h, with 500 ng/ml. A dose of 200 ng/ml is inactive. Beta LPH is lipolytic: 400 and 230 ng/ml, during phase I. At the ratio of the contaminate of HGH h 1000 ng/ml, resultant from hypophysis: 10 ng/ml, the action is less significant. Human growth hormones HGH h and HGH b appear to be: antilipolytic during the first period 0 1 h 30 with 1000 and 300 ng/ml, and, then lipolytic between 1 h 30 and 4 h with 1000, 300 and 100 ng/ml. The effect is pure with HGH b during the two periods, and, principally, during phase I when there is an absence of lipolytic contaminate. Biphasic action: antilipolytic, lipolytic, ascertained with a pure growth hormone: HGH b "in vitro" represents an effect "per se", non mediated by an eventual "in vivo" action of somatomedins.     

Suppressive effect of L-dopa on human prolactin release during sleep.

Immunoreactive plasma human prolactin (HPr) and human growth hormone (HGH) concentrations were measured in six normal young men with polygraphic sleep monitoring during normal sleep and during sleep in which l-dihydroxyphenylalanine (l-DOPA) was infused intravenously at a rate of 0.8 to 1.0 mg/min. The intravenous infusion of l-DOPA significantly suppressed the episodic release of HPr during sleep and the occurrence of rapid eye movement (REM) sleep. However, HGH release during sleep was not remarkably influenced by l-DOPA. These results suggest that central catecholaminergic neural mechanisms are related to both sleep-related HPr release and REM sleep, but do not play an important role in sleep-related HGH release.     

THYROTROPHIN RESPONSES TO INTRAVENOUS THYROTROPHIN-RELEASING HORMONE IN PATIENTS WITH HYPOTHALAMIC AND PITUITARY DISEASE

Plasma immunoreactive thyrotrophin (TSH) responses to synthetic thyrotrophin releasing hormone (TRH) have been measured in forty-five patients with pituitary or hypothalamic disease (largely non-functioning and functioning pituitary tumours) tested before and/or after ablative treatment. Subnormal TSH responses usually indicated impaired pituitary function but were less sensitive indices than those of human growth hormone (HGH) after hypoglycaemia. High basal TSH values with exaggerated rises after TRH were occasionally found with hypothyroidism and impaired HGH and cortisol secretion. Delayed TSH responses were indicative of hypothalamic disease in some cases, but in others were associated with pituitary tumours without overt hypothalamic disease. Normal TRH tests were found with hypothyroidism, while five abnormal tests (four delayed) were found in euthyroid patients. Patterns of TSH response to TRH in hypothalamic-pituitary disease are complex and their significance is not always clear.     

Plasma growth hormone response to insulin-induced hypoglycemia in diabetes mellitus

Summary Plasma human growth hormone (HGH) response to insulin-induced hypoglycemia was studied in patients with diabetes mellitus and age and sex matched normal subjects. The diabetics comprised two groups: (a) those with retinopathy, (b) those without retinopathy. Adequate hypoglycemia (50% or a greater fall in fasting blood glucose) was achieved by i.v. administration of insulin 0.1 U/kg body weight in normal subjects and 0.2 U/kg in diabetics. Mean fasting plasma HGH levels did not differ significantly between control subjects (1.39 ± 0.25 SEM, ng/ml), diabetics without retinopathy (1.55 ± 0.25) and diabetics with retinopathy (1.81 ± 0.6). There was a significant rise in plasma HGH, following insulin-induced hypoglycemia in all three groups. When mean Δ HGH or sum HGH value in different groups were compared, no significant difference was observed. However, mean HGH-hypoglycemia index (Δ HGH · 100/nadir blood glucose) was significantly lower in the two diabetic groups as compared to that obtained in control subjects, but it was identical in diabetics with or without retinopathy. In 32% of diabetic patients abnormal blood glucose and plasma HGH responses were observed.     

Effect of administered human growth hormone on growth retardation in inflammatory bowel disease

In a previous study of 22 severely growth-retarded children with inflammatory bowel disease (IBD), endocrinologic evaluation revealed hypogonadism and low growth hormone (HGH) levels. This was attributed to a secondary hypopituitarism. In order to assess this hypothesis, two individuals from this group and another similar child who was not so severely growth-retarded as to be included in the initial study were given HGH replacement in an acute trial and for a 6-month interval. No significant height increment could be attributed to the HGH administration although a definite anabolic response was present in each patient during the acute trial. It appears that the youngsters with IBD may have a relative end-organ resistance to the metabolic and growth-promoting effects of HGH and that their growth problems are not related to hypopituitarism.     

Kyolic and Pycnogenol increase human growth hormone secretion in genetically-engineered keratinocytes.

The amount of human growth hormone (HGH) decreases significantly after the age of 30. This decrease has been implicated as one of the major causes in the signs of aging, such as thinning of the skin and bones, a decrease in lean muscle mass and an increase in adipose tissue. Supplementing the body's dwindling supply with recombinant human growth hormone (rHGH) has been shown to reverse the signs and symptoms of aging. However, drawbacks in rHGH replacement therapy include prohibitively high cost, the need for repeated injection and side effects such as carpel tunnel syndrome, gynecomastia and insulin resistance. The purpose of this study was to establish an in vitro model using genetically-engineered keratinocytes to screen natural compounds for the ability to stimulate HGH secretion. We now report that a combination of equal amounts of L-arginine and L-lysine, aged garlic extract (Kyolic), S-allyl cysteine and Pycnogenol significantly increased secretion of HGH in this in vitro model. The data indicate that this in vitro model may be used to screen for other secretagogues.     

Bromocriptine: effect on serum prolactin and growth hormone in psychogeriatric hospital patients

Serum prolactin (PRL) and human growth hormone (HGH) were assessed before, and three hours after oral administration of 2.5 mg of bromocriptine in 39 hospitalized geriatric patients with organic brain syndrome. Serum PRL concentrations decreased significantly irrespective of initial values (also in the 7 geriatric control subjects), but HGH levels were low in all patients and did not change during the three hours after administration of bromocriptine. Closer scrutiny of the HGH responses to bromocriptine in 5 patients and 5 controls showed that the serum HGH response was more variable among the patients than among the controls. The findings are discussed in relation to neuroendocrine changes associated with aging, institutional living, and mental disease.     

Phenformin has opposite effects on insulin and growth hormone binding to IM-9 lymphocytes

We studied simultaneously the effect of various concentrations of phenformin on insulin and growth hormone binding to IM-9 lymphocytes, a cell type known to have receptors for both these hormones. After 24 hr preincubation with phenformin at 2 x 10(-5) M, insulin binding to IM-9 cells was increased by 80.4 +/- 10.5% over control (mean +/- SE of 10 experiments). In parallel experiments HGH binding was decreased by 43.1 +/- 2.2% (mean +/- SE). This effect of phenformin was dose-dependent for both HGH and insulin binding over the concentration range 1.5 x 10(-6) M to 5 x 10(-5) M, and was already detectable 3 hr after phenformin addition. These data indicate that phenformin has an opposite effect on insulin and growth hormone binding to IM-9 cells. Several possible mechanisms might be suggested for the decrease of HGH binding sites induced by phenformin: the simultaneous opposite effect on HGH and insulin receptors raises the possibility that some metabolic event triggered by the drug is able to induce opposite changes in the binding of these two hormones with different biological activities.     

THE HORMONAL RESPONSE TO PHYSICAL EXERCISE

Studies of the hormonal response to physical exercise were performed on young males who were classified as physically fit or unfit. The studies included serial measurements of blood sugar, plasma free fatty acids (FFA), serum growth hormone (HGH), serum insulin, serum glucagon and plasma cortisol levels during and following a 30-minute period of maximal physical exercise. The hormonal response in both groups was similar except in the case of HGH. In both groups there was an elevation of HGH level during exercise, but in the fit group HGH returned to basal levels within 30 minutes, whereas in the unfit group the HGH level continued to rise for a further hour before decreasing. These results confirm that HGH secretion occurs during vigorous muscular exercise, and that in the unfit subject there is a delay in the return of HGH to basal levels following exercise. Studies during submaximal exercise revealed an elevation of HGH only in the unfit group. The possibility of anaerobic metabolites acting as the stimulus for HGH in exercise was investigated by infusion of sodium lactate, which caused a significant elevation of HGH level. From the above data we conclude that a characteristic of physical fitness is a rapid return of HGH secretion to basal levels following vigorous muscular exercise.     

Pituitary and adrenal hormones in patients after myocardial infarction under ergometer load

The levels of human growth hormone (HGH), ACTH and cortisol in the plasma of 100 middle-aged men were measured by means of radioimmunoassay (12 patients in the phase of hospitalization after myocardial infarction, 47 patients in convalescence, 31 patients in post-convalescence, 10 healthy men). Twenty patients in the phase of convalescence and all patients in post-convalescence did exercises on bicycle ergometer with submaximal loading. Patients after myocardial infarction showed significantly lower basic levels of HGH than healthy persons, and the increase in the HGH level induced by exercise was significantly lower. The hormones ACTH and cortisol showed only slight differences. The secretion of the pituitary hormones, mainly HGH, seems to be altered in patients after myocardial infarction.     

Growth hormone response to L-Dopa in diabetes mellitus

Summary The effect of a single oral dose of 0.5 g L-Dopa on the serum levels of human growth hormone (HGH) was studied in 38 diabetics and 15 age and sex matched control subjects. The diabetics were divided into three clinical sub-groups:a) juvenile diabetics, 15;b) maturity onset diabetics, 15; andc) insulin dependent diabetics admitted in a state of ketoacidosis, 8. L-Dopa-induced HGH secretion in juvenile and maturity onset diabetics was studied before and after the control of diabetes mellitus. HGH was estimated by a homologous double antibody radioimmunoassay. The fasting serum HGH in maturity onset diabetics did not differ significantly from that of control subjects; it was significantly higher in juvenile diabetics and in ketotic diabetics during ketosis and after the control of diabetes. In juvenile diabetics the mean fasting serum HGH level decreased after the control of diabetes but was still significantly higher than in normal subjects. L-Dopa caused a significant rise in serum HGH in 14 control subjects. Among the diabetics the HGH response to L-Dopa was either absent or markedly attenuated in the uncontrolled state. After the control of diabetes a significant improvement in HGH response to L-Dopa was evident in juvenile diabetics but no improvement was seen in maturity onset diabetics. There is thus a considerable derangement in HGH secretion in diabetes mellitus. The various possibilities are discussed.     

The many faces of human growth hormone

The story of human growth hormone (hGH) is colorful by drug industry standards. HGH, also known as somatropin, was first used to treat stunted growth in children. Later is was used in people with HIV disease to treatment the gauntness of AIDS-related wasting and, more recently, the fat accumulations associated with lipodystrophy. HGH also may play a role in immune reconstitution. Outside the field of HIV, this very expensive therapy has multiple indications. Unapproved uses for hGH run the gamut from muscle enhancer to purported cure-all. Not surprisingly, the man-made hormone does not always perform as desired. Yet new research into how hGH may fit into the future of HIV disease management warrants another look at this unusual drug.     

Effect of alcohol administration on plasma growth hormone response to insulin-induced hypoglycemia.

Plasma growth hormone (HGH) response to insulin-induced hypoglycemia was assessed in a group of normal adult volunteers, with and without prior consumption of ethanol. A significant difference was found in peak HGH concentrations on the two occasions, indicating that prior consumption of ethanol attenuates the normal HGH response to insulin-induced hypoglycemia. It is suggested that ethanol may deplete catecholamine stores in the neurons of the ventromedial nucleus of the hypothalamus and may thereby impair secretion of growth hormone releasing factor. Under certain circumstances this could be of importance in the pathogenesis of alcohol-induced hypoglycemia.