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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.
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PMID:Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies. 876 5

Changes in food intake, serum adipsin, and obesity were evaluated in the MSG-treated mouse. In Experiment 1, mice treated with MSG had 50% lower serum adipsin and over 2-fold higher percentage of body fat than the lean controls. Both feeding caffeine and restricting intake normalized serum adipsin and caused weight loss, but did not normalize the percentage of body fat. No additional effect was gained by feeding isoproterenol or ephedrine in combination with caffeine. In Experiment 2, we separated the direct effect of caffeine from the associated depression in intake using a paired feeding design, and also determined the effects of selected adrenergic agents and somatotropin (S). Somatotropin increased weight gain and reduced the percentage of body fat in healthy and obese mice, and tended to lower serum adipsin. Caffeine clearly depressed intake, caused weight loss, and increased serum adipsin, but similar results were achieved by restricting intake. None of the adrenergic drugs tested changed serum adipsin. Ephedrine depressed food intake and caused weight loss, but reduced the percentage of body fat only at the highest dietary concentration (2000 mg per kg of diet). Phenylephrine reduced weight gain without a concomitant effect on the percentage of body fat, and isoproterenol did not influence weight gain or body fat.
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PMID:Regulation of adipsin and body composition in the monosodium glutamate (MSG)-treated mouse. 891 74

Growth hormone (GH) secretion is reduced with age in normal subjects. Aging is furthermore associated with a decline in lean body mass and an increase in relative adiposity, and overt obesity is a negative determinant of GH secretion in all age groups. We tested the hypothesis that differences in body composition and physical fitness rather than age determine stimulated GH secretion in healthy adults. Forty-two clinically nonobese adults [22 women and 20 men, mean age 39.4 yr (range 27-59), mean +/- SE body mass index (BMI) = 23.9 +/- 0.5 kg/m2] underwent 2 GH stimulation tests (arginine and clonidine), determination of maximal oxygen consumption (VO2-max), and a number of anthropometric measurements: body mass index (BMI), waist to hip (W/H)-ratio, intraabdominal fat and thigh muscle to fat (M/F)-ratio (computed tomography scan), total body fat, and lean body mass (DEXA scan). Peak GH levels were lower with clonidine [mean +/- SE (micrograms/L): 9.79 +/- 1.29 (arginine) vs. 3.56 +/- 0.57 (clonidine) (P < 0.001)]. Arginine-stimulated GH peak levels correlated negatively with indices of adiposity and age [intraabdominal fat: r = -0.72, P < 0.001; W/H-ratio: r = -0.58, P < 0.001; age: r = -0.54, P < 0.001], and positively with VO2-max [r = 0.60, P < 0.001]. Clonidine-stimulated GH peak correlated negatively with intraabdominal fat [r = -0.60, P < 0.001] and age [r = -0.46, P = 0.008]. Multiple linear regression revealed multicollinearity among several of the independent variables. In all equations abdominal adiposity and physical fitness, rather than age, contributed significantly to predict changes in arginine stimulated GH secretion. Intraabdominal fat was a more important determinant of the clonidine evoked GH response than age. In clinically nonobese, healthy adults relative adiposity, in particular in the abdominal region, is a major negative determinant of stimulated GH secretion, and physical fitness is an important positive predictor. The cause-effect relationship of these observations remains to be elucidated, but our findings may have clinical implications in the diagnosing of GH-deficiency in adults.
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PMID:Abdominal adiposity and physical fitness are major determinants of the age associated decline in stimulated GH secretion in healthy adults. 896 53

A relationship exists between obesity and non-insulin-dependent diabetes mellitus. Central, abdominal obesity carries a particularly high risk that is most likely associated with enlargement of visceral fat deposits. A multiple endocrine perturbation is associated with visceral obesity. This consists of a hypersensitive hypothalamic-pituitary-adrenal (HPA) axis, with resulting excess of cortisol secretion upon stimulation. Growth hormone levels in both sexes are diminished and testosterone concentrations in men are lower than normal. In women a moderate hyperandrogenism is often present. The elevated sensitivity of the HPA axis may be a primary event, followed by adrenal androgen production in women and by interaction at several levels, with inhibition of both the growth hormone and pituitary-gonadal axes. Together, these endocrine perturbations seem to be able to centralize body fat to visceral depots because of a high density of steroid hormone receptors. The endocrine perturbations are most likely followed by insulin resistance. Elevated cortisol levels, deficiencies in sex-specific steroid hormones and excess androgens result in insulin resistance. The endocrine abnormalities in visceral obesity are followed by insulin resistance, both directly and indirectly via contribution of excess free fatty acids from centralized body fat depots. The hyperactivity of the HPA axis may be due to frequent challenges and it is amplified by a deficient feedback inhibition. A depressive, helplessness reaction to stress may be involved. Such stress factors may be found in socioeconomic and psychosocial handicaps, as suggested by results of population studies. This hypothesis is strongly supported by the reproduction of an identical condition in non-human primates that react with a depressive reaction upon psychosocial types of stressors. The perturbations of the HPA axis may thus be in the centre of the syndrome. Studies of this axis in established non-insulin-dependent diabetes mellitus suggest similar perturbations, but the information is not conclusive.
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PMID:The origins and consequences of obesity. Diabetes. 901 75

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. Growth hormone (GH) secretion is markedly influence by body weight being markedly suppressed in obesity and underweight. The aim of the present study was to study whether leptin can act as a metabolic signal connecting the adipose tissue with the growth hormone axis. We administered leptin antiserum (10 ul, i.c.v.) or normal rabitt serum (NRS; 10 ul, i.c.v.) to freely moving fed rats. Furthermore we assessed the effect of leptin administration (10 ug, i.c.v.) on fed and fasted rats. Spontaneous GH secretion was assessed over 6 hours with blood samples taken every 15 min. Administration of leptin antiserum led to a decrease in spontaneous GH secretion as assessed by the area under the curve (AUC) (168+/-72 ng/ml/6h) in comparison to NRS-treated rats (813+/-179 ng/ml/6h, p<0.01). While leptin administration (10 ug/rat; i.c.v.) to normal fed rats did not modify spontaneous GH secretion, leptin administration to fasted rats led to a reversal of the inhibitory effect exerted by fasting on GH secretion (AUC, 1650+/-351 ng/ml/6h vs 77+/-32 ng/ml/6h, p<0.01). This data suggests that leptin is a metabolic signal that regulates GH secretion.
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PMID:Regulation of in vivo growth hormone secretion by leptin. 911 21

Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration: in fact, prolonged administration of GHRPs increases IGF-1 levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and decreases thereafter. By the sixth decade of life, the activity of GHRPs is reduced but it is still marked and higher than that of GHRH. The GH-releasing activity of GHRPs is synergistic with that of GHRH, is not affected by opioid receptor antagonists, such as naloxone, and is only blunted by inhibitory influences, including neurotransmitters, glucose, free fatty acids, gluco corticoids, recombinant human GH and even exogenous somatostatin, which are known to almost abolish the effect of GHRH. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states such as in acromegaly, anorexia nervosa and hyperthyroidism. On the other hand, their good GH-releasing activity has been shown in some but not in other somatotrope hyposecretory states. In fact, reduced GH responses after GHRP administration have been reported in idiopathic GH deficiency as well as in idiopathic short stature, in obesity and in hypothyroidism, while in patients with pituitary stalk disconnection or Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. In short children an increase in height velocity has also been reported during chronic GHRP treatment. Thus, based on their marked GH-releasing effect even after oral administration, GHRPs offer their own clinical usefulness for treatment of some GH hyposecretory states.
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PMID:Growth hormone-releasing peptides. 918 61

A gender-related impairment of the somatotrophic axis is present in obese Zucker rats, female rats being better preserved than males. We showed that another animal model of obesity, i.e., male rats made obese by feeding a hypercaloric diet had a reduced function of somatotrophic axis which was likely related to impairment of gonadal function. Aim of this work was that of studying the function of somatotrophic axis in female overfed rats and comparing it to that of male rats of the previous study. Sprague-Dawley female rats were fed an energy-rich palatable diet for seven months. At the end of overfeeding, according to the degree of overweight, rats were divided into overtly obese (Obese), overweight (Overweight) and Non-Obese, i.e. rats whose weights were similar to those of controls. Rats fed ad libitum with the standard pellet chow served as controls (Controls). Acute administration of a supramaximal dose of GHRH (2 microg/rat, iv) elicited a plasma GH rise similar to that of Controls in all the groups, except in Obese which had a lower GH response. Growth hormone responses after GHRH administration were inversely related to plasma levels of free fatty acids (FFA). Pituitary GH content and gene expression as well as hypothalamic GHRH and SS mRNA content, were similar in all experimental groups and in Controls and the same was true for plasma concentrations of free IGF-I. These results indicate that, similarly to obese female Zucker rats, also overfed female rats had a better preservation of the somatotrophic axis than their male counterparts. In diet-induced obese rats, also the etiology of the impairment of somatotrophic axis seems to be gender-related i.e. due to a reduction of gonadal function in males and to an elevation of FFA in females.
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PMID:Hypothalamo-pituitary-IGF-1 axis in female rats made obese by overfeeding. 928 81

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) metabolism may be disturbed in obese children. We investigated serum GH, IGF-I, IGF-binding protein-3 (IGFBP-3) levels in 42 obese and 40 non-obese healthy children aged 6-14 years. GH stimulation tests with L-dopa and insulin were performed. Serum IGF-I levels were studied by immunoradiometric assay (IRMA) and IGFBP-3 levels by radioimmunoassay (RIA). IGF-I levels were significantly higher in the obese group (p < 0.05), but IGFBP-3 levels were not different from the control group. IGF-I and IGFBP-3 levels were significantly higher in the obese pubertal children than in the obese prepubertal ones (p < 0.05). A positive linear correlation was found between body mass index (BMI) and IGF-I levels (r = 0.51, p < 0.05). These results suggest that obesity may have a considerable effect on IGF-I.
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PMID:Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in obese children. 938 22

Growth hormone-releasing peptides (GHRPs) are a series of hepta (GHRP-1)- and hexapeptides (GHRP-2, GHRP-6, Hexarelin) that have been shown to be effective releasers of GH in animals and humans. More recently, a series of nonpeptidyl GH secretagogues (L-692,429, L-692,585, MK-0677) were discovered using GHRP-6 as a template. Some cyclic peptides as well as penta-, tetra-, and pseudotripeptides have also been described. This review summarizes recent developments in our understanding of the GHRPs, as well as the current nonpeptide pharmacologic analogs. GHRPs and their analogs have no structural homology with GHRH and act via specific receptors present at either the pituitary or the hypothalamic level. The GHRP receptor has recently been cloned and it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. Although the exact mechanism of action of GHRPs has not been fully established, there is probably a dual site of action on both the pituitary and the hypothalamus, possibly involving regulatory factors in addition to GHRH and somatostatin. Moreover, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. The marked GH-releasing activity of GHRPs is reproducible and dose-related after intravenous, subcutaneous, intranasal, and even oral administration. The GH-releasing effect of GHRPs is the same in both sexes, but undergoes age-related variations. It increases from birth to puberty and decreases in aging. The GH-releasing activity of GHRPs is synergistic with that of GHRH and not affected by opioid receptor antagonists, while it is only blunted by inhibitory influences that are known to nearly abolish the effect of GHRH, such as neurotransmitters, glucose, free fatty acids, glucocorticoids, rhGH, and even exogenous somatostatin. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states, such as acromegaly, anorexia nervosa, and hyperthyroidism. On the other hand, GHRPs and their analogs have been reported to be effective in idiopathic short stature, in some situations of GH deficiency, in obesity, and in hypothyroidism, while in patients with pituitary stalk disconnection and in Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. A potential role in the treatment of short stature, aging, catabolic states, and dilated cardiomyopathy has been envisaged.
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PMID:Growth hormone-releasing peptides and their analogs. 946 89

Growth hormone secretagogues (GHS) are synthetic, non-natural peptidyl and nonpeptidyl molecules with potent stimulatory effect on somatotrope secretion. They have no structural homology with growth hormone-releasing hormone (GHRH) and act via a specific receptor, which has now been cloned and is present at both the pituitary and hypothalamic level. This evidence strongly suggests the existence of a still unknown natural GHS-like ligand. Several data favour the hypothesis that GHS could counteract somatostatinergic activity at both the pituitary and hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that they act via an unknown hypothalamic factor remains open. GH-releasing peptide-6 (GHRP-6) is the first hexapeptide studied extensively in humans. More recently, peptidyl superanalogues GHRP-1, GHRP-2 and hexarelin, and nonpeptidyl mimetics, such as the spiroindoline derivative MK-677, have been synthesized and their effects have been studied in humans. The GH-releasing activity of GHS is marked, dose related and reproducible after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHS is partially desensitized but prolonged, intermittent oral administration increases insulin-like growth factor I (IGF-I) levels. The GH-releasing effect of GHS undergoes age-related variations; it increases from birth to puberty, remains similar in adulthood and decreases with ageing. The effect of GHS on GH release is synergistic with that of GHRH, while it is only partially refractory to inhibitory influences, which nearly abolish the effect of GHRH. GHS maintain their GH-releasing activity in some somatotrope hypersecretory states such as acromegaly, anorexia nervosa, hyperthyroidism and critical illness. The GH response to GHS has been reported clear although reduced in GH deficiency, obesity and hypothyroidism, while it is strongly reduced in patients with pituitary stalk disconnection or Cushing's syndrome. In short children, elderly subjects, critically ill patients and even in adult patients with GH deficiency an increase of IGF-I has been shown after GHS treatment. These data indicate that treatment with orally active GHS in humans enhances the activity of the GH-IGF-I axis and could be clinically useful.
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PMID:Orally active growth hormone secretagogues: state of the art and clinical perspectives. 966 94


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