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.     

In vitro activation of neutrophils of the aged by recombinant human growth hormone.

Several functions of polymorphonuclear neutrophils (PMNL) have been found to be altered in the aged. As the neuroendocrine network, in particular growth hormone (GH), may interfere with the regulation of nonspecific host defense mechanisms, a recently described PMNL-priming activity of recombinant human (rH) GH in vitro was investigated. Oxidative metabolism of PMNL from young and old subjects was studied by measuring reduction of nitroblue tetrazolium (NBT) or cytochrome c. In the absence of stimulating agents, PMNL from old subjects reduced NBT to a significantly lesser extent than did PMNL from young subjects. Addition of rHGH to PMNL from old subjects reversed the suppressed spontaneous oxidative metabolism. No differences between young and old were observed for the increase of stimulated oxidative metabolism. The results suggest that altered PMNL function in the aged may be reversed by rHGH and that the ability of PMNL to respond to rHGH does not decline with age.     

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.     

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.     

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.     

Adjuvant effect of human growth hormone with an inactivated flavivirus vaccine

Vaccines made by inactivating pathogenic microorganisms have been dramatically successful in controlling diseases in humans and animals. Despite their successes, they have a major disadvantage in that several inoculations are required for them to be effective. To overcome this problem, a commercial inactivated vaccine preparation against tickborne encephalitis was combined with human growth hormone (HGH). This formulation produced complete protection in a murine model with only one dose of vaccine, apparently by binding hormone and antigen to an insoluble matrix containing aluminium hydroxide. Thus it is postulated that when virus-specific lymphocytes are attracted to the site of injection, the hormone is at a high local concentration and stimulates the clonal expansion of antigen-specific T cells. The development of genetically engineered HGH now gives unlimited supplies of hormone, potentially resulting in an increase in efficacy of a wide variety of vaccines, especially those needing prolonged immunization schedules such as those being developed to combat human immunodeficiency virus infection.     

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.     

Dietary regulation of human growth hormone secretion

The effect of diet on the secretion of human growth hormone (HGH) was investigated in eight normal subjects—each studied before and after four separate dietary regimens. A high-carbohydrate (525 g) diet of 3600 cal containing 75 g of protein for 23 days suppressed completely arginine-initiated HGH secretion. While subjects were ingesting a control diet, the mean maximal response to arginine was 21.5 ± 3.5 mμg/ml vs. 4.6 ± 0.9 mμg/ml (p < 0.01) following the experimental diet ($\text{X}$ ± SEM). The latter value did not differ from the mean maximal HGH response occurring “spontaneously” after control infusion of saline (3.5 ± 0.9 mμg/ml). This suppression of HGH secretion appeared related to the amount of carbohydrate rather than the total caloric level. An identical pattern occurred when carbohydrate was proportionately the same, but total intake was reduced to 2300 cal. With a high-carbohydrate diet of 2300 cal, the mean maximal HGH response to arginine was 4.7 ± 1.1 mμg/ml vs. a control response of 21.4 ± 4.7 mμg/ml (p < 0.01). Twenty-four-hour secretory patterns of HGH were assessed in three subjects befor and after the high-carbohydrate diet of 2300 cal. Overall HGH secretion was reduced significantly at the termination of the 23-day experimental period in two of these three subjects. HGH secretion was, likewise, significantly reduced by high-carbohydrate diets containing less protein. The change of HGH secretion could not be related in any study to differences in plasma-free fatty acid (FFA) or glucose concentration. FFA concentrations did decline in the first 3–7 days of each experimental period, but returned to basal values 7–8 days prior to reassessment of HGH secretion. Plasma glucose concentrations did not change significantly at any time.     

EFFECT OF l-DOPA ON THE SECRETION OF PLASMA GROWTH HORMONE IN CHILDREN AND ADOLESCENTS

The stimulation of growth hormone release in children by L-dopa has been studied. An oral dose of 0.5 g L-dopa was administered to fourteen children with, and to fifteen children without, hypothalamic-pituitary insufficiency. In the control group, L-dopa induced a release of pituitary growth hormone, the peak of which occurred from 30 to 60 min after ingestion. Nine out of fifteen control subjects showed peak levels of plasma growth hormone greater than 8 ng/ml. None of the patients with hypothalamic-pituitary insufficiency showed levels greater than 5 ng/ml. In five out of six children with measurable amounts of plasma HGH, and in fourteen children with a lack of HGH, there was a good correlation between the HGH response after L-dopa, insulin hypoglycaemia and arginine infusion. It is concluded that the administration of one oral dose of L-dopa can be used as a provocative test of growth hormone secretion.     

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.     

Evaluation of propranolol-glucagon test

A propranolol-glucagon test was evaluated in 24 control normal children, 21 pituitary dwarfs, 15 patients with constitutional short stature, 2 with chromosome aberration and 4 with miscellaneous diseases. The dose of glucagon enough for the stimulation of human growth hormone (HGH) secretion is more than 20 microgram/kg of body weight. During the test in the control subjects the serum HGH level increased from 2.3 +/- 1.2 ng/ml to a maximum level of 30.0 +/- 15.1 ng/ml, when 10 mg propranolol, regardless of body weight and 30 microgram glucagon per kg of body weight are given. The dose of propranolol administered ranged from 0.2 to 1.0 mg/kg of body weight in normal children studied. Serum 11-OHCS also increased significantly from 14.5 +/- 11.2 microgram/100 ml to 30.1 +/- 15.5 microgram/100 ml (P less than 0.01). There was no difference in the maximum level of urinary total catecholamines in propranolol-glucagon test between 7 pituitary dwarfs and 7 control subjects. The mechanism of HGH response to propranolol-glucagon administration is unknown, but propranolol-glucagon administration is a sensitive and reliable provocative test for HGH secretion, since false negative response of HGH are not observed in patients with non-pituitary disease.     

Human growth hormone and cortisol response to insulin stimulation in aging.

The influence of age on plasma growth hormone (HGH) and cortisol response to i.v. insulin (0.1 U/kg of body weight) was evaluated in 32 healthy subjects whose ages ranged between 20 and 84 years. A significant reduction in HGH response to insulin was observed with aging. In the young (20-34 years), middel-aged (35-49 years), and elderly (53-84 years) groups, average HGH peaks were 46.51 +/- 7.37, 29.95 +/- 5.35, and 14.31 +/- 2.39 ng/ml while average HGH areas were 2.911 +/- 0.484, 1.654 +/- 0.316, and 0.699 +/- 0.149 mug-min, respectively. Since insulin's hypoglycemic effect became less rapid with aging, this could, in part, explain the progressive decline in the HGH response to insulin. This phenomen may also be attributed to histological changes occurring in the pituitary with aging. Moreover, cortisol response was similar to all three age groups. These findings suggest that, while HGH response to insulin is correlated with age, adrenal response does not show any important modifications with aging.     

The skin as a mirror of the aging process in the human organism--state of the art and results of the aging research in the German National Genome Research Network 2 (NGFN-2)

As our society is growing older, the consequences of aging have begun to gain particular attention. Improvement of quality of life at old age and prevention of age-associated diseases have become the main focus of the aging research. The process of aging in humans is complex and underlies multiple influences, with the probable involvement of heritable and various environmental factors. In particular, hormones are decisively involved in the generation of aging. Over time, important circulating hormones decline due to a reduced secretion of the pituitary, the adrenal glands and the gonads or due to an intercurrent disease. Among them, serum levels of growth factors and sexual steroids show significant aging-associated changes. Within the scope of the Explorative Project 'Genetic aetiology of human longevity' supported by the German National Genome Research Network 2 (NGFN-2) an in vitro model of human hormonal aging has been developed. Human SZ95 sebocytes were maintained under a hormone-substituted environment consisting of growth factors and sexual steroids in concentrations corresponding to those circulating in 20- and in 60-year-old women. Eight hundred and ninety-nine genes showed a differential expression in SZ95 sebocytes maintained under the 20- and 60-year-old hormone mixture, respectively. Among them genes were regulated which are involved in biological processes which are all hallmarks of aging. The most significantly altered signaling pathway identified was that of the transforming growth factor-beta (TGF-beta). A disturbed function of this cascade has been associated with tumorigenesis, i.e. in pancreatic, prostate, intestine, breast, and uterine cancer. Interestingly, genes expressed in signaling pathways operative in age-associated diseases such as Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and amyotrophic lateral sclerosis (ALS) were also identified. These data demonstrate that skin and its appendages may represent an adequate model for aging research. Hormones interact in a complex fashion, and aging may be partly attributed to the changes in their circulating blood levels. Furthermore, a disturbed hormone status may partially act towards the manifestation of neurodegenerative diseases. Thus, these results could be a basis for an integrated and interdisciplinary approach to the analysis of the aging process.     

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.     

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.     

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.     

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.     

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。     

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.     

Daily production and metabolic clearance of growth hormone in juvenile diabetes mellitus

Summary Daily production (PR) of human growth hormone (HGH) was calculated in patients with juvenile diabetes and control subjects by determining metabolic clearance rate (MCR) of¹³¹I HGH, at equilibrium, and mean endogenous HGH levels throughout a 24 h day. Half hourly sampling or a constant withdrawal pump were used to obtain an integrated mean endogenous HGH level. MCR (liters/day) was significantly reduced in all diabetic subjects both in absolute terms (96 ± 15 vs 274 ± 37) and relative to surface area (62 ± 8 vs 171 ± 21) (p < 0.01). Mean HGH levels were 8.4 ng/ml in the diabetics and 5.5 ng/ml in age matched controls. Daily HGH PR in the diabetic subjects (339 to 1365 g/day) did not exceed values in the control subjects (1005–1426 g/day). The results indicate that the elevated plasma HGH levels and increased HGH response to stimuli observed in diabetes, reflect reduced metabolic clearance, rather than increased pituitary secretion.