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 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.     

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。     

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.     

Growth and body composition in intrauterine growth retardation (IUGR) before and during human growth hormone administration

The influence of exogenous HGH upon the size and number of muscle cells, nitrogen retention on a nitrogen balance study, and linear growth were evaluated in eight children with intrauterine growth retardation. Before treatment, these patients were all significantly short and had decreased muscle nuclear number for age. On HGH treatment, linear growth increased significantly over previous growth rates, nitrogen retention occurred, and the muscle cells responded with an increase in cell multiplication but without an increase in cell size. These children, therefore, were capable of response to HGH, since cell multiplication but not cytoplasmic growth are ascribed to HGH.     

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.     

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.     

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.     

Leukemia in a patient treated with growth hormone

It is well known that growth hormone (GH) therapy is associated with increased risk of development of malignant tumors, especially leukemia. In the case presented, growth hormone treatment was initiated in a 25-year-old patient with hypopituitarism. After 4 months of therapy with thrice a week injections of rhGH, acute myelogenous leukemia developed. It was thought that no clearcut evidence existed to establish a relationship between the growth hormone treatment and development of acute leukemia.     

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.     

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.     

Metabolic disorders in myocardial infarction. Changes in blood serum zinc, growth hormone, insulin and glucose concentration in patients with acute myocardial infarction.

The authors examined the concentrations of zinc, HGH, insulin and glucose in blood serum of 40 patients with acute myocardial infarction. Zinc and HGH concentrations in blood serum correlated well with changes in the clinical state in these patients. The more severe the condition of the patient, the greater zinc concentration fall and HGH concentration rise in blood serum were noted. All the changes were statistically significant (P less than 0.001) in cases of severe clinical course and most distinct in cardiogenic shock. On the other hand, in MI of mild course, zinc concentration fall in blood serum was not accompanied by HGH rise. A positive correlation between the concentrations of zinc and HGH found in normal subjects became negative in patients with acute MI of severe course. The changes of zinc and HGH concentrations seem to be due to the non-specific effect of acute myocardial stress, particularly enhanced in MI with severe course and cardiogenic shock, Observation of the intensity of changes may have prognostic significance due to the fact that they were most distinctive in MI of most severe course.     

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.     

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.     

Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease

Background: Platelet-derived endothelial cell growth factor (PD-ECGF) is reported to be highly expressed in tumors and inflammatory tissues, but its expression and role in inflammatory bowel disease (IBD) are still unclear. In this study we examined the location and tissue density of cells immunoreactive for PD-ECGF in the colonic mucosa of IBD. Methods: Paraffin-embedded sections of colonic tissue from patients with ulcerative colitis (UC) or Crohn's disease (CD) were immunostained for PD-ECGF. As controls, noninflamed mucosa of IBD, as well as normal colonic mucosa from patients with colorectal cancer, were used. Also, cancer tissues were evaluated. In addition, changes in the expression of PD-ECGF in human umbilical vein endothelial cells (HUVEC) after treatment with inflammatory cytokines and angiogenic factors, as well as after coculture with colon cancer cell lines, were evaluated by flow cytometry. Results: In normal colonic mucosa and noninflamed mucosa of IBD, PD-ECGF expression was negligible. In inflamed colonic mucosa, strong expression was observed, predominantly in macrophages and fibroblasts. Vascular endothelial cells of the inflamed colonic mucosa, but not of normal colonic mucosa or of neoplastic tissues, stained for PD-ECGF, and the microvessel density was significantly increased in the severely inflamed mucosa. Flow cytometry demonstrated that PD-ECGF was constitutively expressed in HUVEC. Inflammatory cytokines and vascular endothelial growth factor (VEGF) increased its expression, whereas basic fibroblast growth factor (bFGF) decreased it. Coculture with colon cancer cell lines in direct contact, but not in those without contact, also resulted in an important decrease in the expression of PD-ECGF in HUVEC. Conclusions: Autocrine production of PD-ECGF by endothelial cells may be a mechanism of inflammatory angiogenesis, but not tumor angiogenesis, and may be particularly important for the maintenance of damaged vasculature in IBD. Received: September 17, 2001 / Accepted: September 6, 2002 Acknowledgments. This study was supported partly by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and partly by a grant from the Ministry of Health, Labour, and Welfare of Japan. Reprint requests to: S. Saito, Present address: Department of Surgery, Chigasaki Municipal Hospital, 5-15-1 Honson, Chigasaki 253-0042, Japan     

Effect of pituitary ultrasonic treatment on plasma human growth hormone levels in diabetic retinopathy and acromegaly

Summary Sixteen diabetic patients presenting advanced retinopathy and 6 patients with acromegaly underwent ultrasonic treatment (UST) of the pituitary, according to Arslan’s method. In the diabetic retinopathy patients, circadian variations of plasma human growth hormone (HGH) levels were studied as well as the response to insulin stimulation, previous to and 7 days after the operation. Five patients were also studied 3 months post-ultrasonic treatment. Preoperative HGH plasma levels were normal and no reduction was observed following operation. Acromegalic patients were rested for oral glucose tolerance and insulin response, before and 7 days after operation. High pre-operatory HGH levels fell appreciably after operation, but the reduction was not significant. Our data demonstrate that high plasma levels of HGH are not always found in diabetes and that even after UST of the pituitary, there does not seem to be a relationship between degree of pituitary inhibition and clinical results. On the other hand, ultrasonic treatment of the pituitary in acromegalic patients determines partial hypophyseal inhibition. Research carried out with C.N.R. funds, Contract No. 73.00507.04.     

Transforming growth factor-beta and hepatocyte growth factor plasma levels in patients with inflammatory bowel disease

OBJECTIVE: An increased mucosal expression of transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) has been reported in patients with active inflammatory bowel diseases (IBD) and in proximity to injured gastric and intestinal mucosal surfaces. The aim of this study was to measure systemic concentrations of TGF-beta and HGF and to assess their potential value to predict disease activity or severity of inflammation in patients with inflammatory bowel diseases. DESIGN AND METHODS: Plasma HGF and TGF-beta1 peptide levels were determined in 29 patients with ulcerative colitis, 45 patients with Crohn's disease and 28 healthy controls using commercial ELISA assays. Peptide levels were correlated with disease activity indices and various laboratory parameters. RESULTS: HGF and TGF-beta1 plasma levels were detected in all control and IBD subjects. Although a tendency towards increased HGF and TGF-beta1 peptide levels in IBD patients was observed, differences between groups were not significant In ulcerative colitis patients HGF plasma levels positively correlated with white blood cell counts and negatively correlated with serum albumin concentrations and haematocrit. In Crohn's disease patients, a positive correlation between TGF-beta and platelet count was observed. CONCLUSIONS: HGF and TGF-beta1 plasma concentrations are not significantly different in IBD and healthy control subjects. Stratification of IBD patients according to disease activity did not reveal any substantial differences, suggesting that HGF and TGF-beta plasma levels have no value in the assessment of disease activity or severity of inflammation in patients with IBD.     

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.     

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.     

Human growth hormone abuse in male weightlifters

In a study of performance-enhancing substance use among 231 experienced young male weightlifters, we found that 27 (12%) reported illicit use of human growth hormone (HGH) or its bioactive derivative, insulin-like growth factor-1. All of these 27 men also reported use of anabolic-androgenic steroids (AAS) and 22 (81%) met criteria for current or past AAS dependence. Fifteen (56%) also reported current or past dependence on opioids, cocaine, and/or ecstasy. These findings suggest that among young male weightlifters, illicit HGH use has become a common form of substance abuse, frequently associated with both AAS dependence and classical substance dependence.