The effect of alpha-MSH on plasma growth hormone, cortisol and TSH in children.

The effect of synthetic alpha-MSH injected intravenously in a uniform dose of 3 mg was studied in 19 prepubertal children. A marked growth hormone (GH) response was seen only in 2 out of 8 constitutionally small children with a normal GH response to insulin and arginine stimulation. Three of of 11 children suffering from hypopituitarism with documented GH and other hormone deficiencies, unexpectedly, showed a significant rise of GH after alpha-MSH: all three had craniopharyngiomas. Alpha-MSH led to an increase of plasma cortisol in all except 3 patients who had secondary adrenal insuffciency. The increase of cortisol after alpha-MSH and after insulin was of the same extent: but the hypoglycemia and stress responsible for the insulin effect were not observed after alpha-MSH. It is possible that alpha-MSH acts by an ACTH-like direct stimulation on the adrenals. There was no effect of alpha-MSH on plasma TSH or on blood glucose.     

Long-term trophic action of alpha-melanocyte-stimulating hormone on the zona glomerulosa of the rat adrenal cortex

The effects of alpha-melanocyte-stimulating hormone (alpha-MSH) on the rat adrenal cortex were investigated by coupled morphometric and radioimmunological techniques. Short-term alpha-MSH administration provoked a significant increase in the aldosterone plasma level along with a notable lipid droplet depletion in zona glomerulosa cells. Long-term alpha-MSH treatment induced a notable hypertrophy of zona glomerulosa cells and a further rise in the blood concentration of aldosterone. alpha-MSH did not affect zona fasciculata morphology and corticosterone plasma level. The possibility is discussed that alpha-MSH may be specifically involved in the control of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.     

Actions of desacetyl-alpha-melanocyte-stimulating hormone on human adrenocortical cells

The responses of human adrenocortical cells to stimulation by ACTH(1-24), desacetyl-alpha-MSH, alpha-MSH and angiotensin II amide have been compared. Both desacetyl-alpha-MSH, thought to be the major form of the peptide in the human pituitary and in circulating plasma, and alpha-MSH caused a significant stimulation of aldosterone, corticosterone and cortisol secretion. Significant stimulation of the production of these steroids was obtained with desacetyl-alpha-MSH at a concentration of 1 nmol/l, while the response to alpha-MSH was considerably less sensitive, with a minimum effective concentration of 0.1 mumol/l. These values compared with minimum effective concentrations of 1 pmol/l for ACTH and 0.1 mumol/l for angiotensin II amide. Although cell types were not separated, it is possible to conclude that none of the peptides showed any specificity for the zona glomerulosa, and in each case the same minimum effective concentration of peptide was required for both aldosterone and cortisol secretion. Yields of steroid obtained under conditions of maximal stimulation by ACTH(1-24), alpha-MSH and desacetyl-alpha-MSH were at least three to five times the basal output of aldosterone, four to eight times that for corticosterone and more than seven to sixteen times that for cortisol. Angiotensin II amide was a relatively poor stimulant with maximal stimulation only 1.5 x basal. In these experiments the minimum effective concentration for desacetyl-alpha-MSH (1 nmol/l) was close to the circulating concentration of desacetyl-alpha-MSH (0.3 nmol/l) in man, and it is thus possible that this peptide may have a physiological role in the control of adrenocortical function.     

Plasma profiles of adrenocorticotropic hormone, cortisol, alpha-melanocyte-stimulating hormone, and growth hormone in dogs with pituitary-dependent hyperadrenocorticism before and after hypophysectomy

The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.     

Plasma aldosterone response to acute stimulation in panhypopituitarism

The influence of acute stimulation by ACTH, upright posture and angiotensin II on plasma aldosterone levels was assessed in human panhypopituitarism. While stimulation by ACTH in hypopituitary patients induced a plasma aldosterone increase similar to that observed in healthy controls, stimulation by upright posture or by infusion of angiotensin II resulted in a lower plasma aldosterone response than in controls in most of the patients. These results suggest that the presence of an anterior pituitary hormone, most likely ACTH, directly or indirectly exerts a permissive action on aldosterone secretion in man.     

Different effects of exogenous cyclic adenosine monophosphate and its dibutryl derivative on plasma growth hormone, glucose, insulin and cortisol.

The effects of the infusion in four different dosages (0.001, 0.005, 0.02 and 0.2 mg/kg/min during 60 min) of cyclic 3',5'-adenosine monophosphate and of its dibutyryl derivative on plasma growth hormone and on glucose, immunoreactive insulin and cortisol were studied in 38 normal subjects and in 10 patients with idiopathic hypopituitarism. In normal subjects cyclic 3',5'-adenosine monophosphate provokes an increase in plasma growth hormone levels (only when a dosage of 0.2 mg/kg/min is used) without any changes in plasma glucose, insulin and cortisol. The maximal value of the means is observed 75 min after starting the infusion. Dibutyryl cyclic 3',5'-adenosine monophosphate (0.2 and 0.02 mg/kg/min) provokes a dose-related rise in plasma growth hormone levels which is always preceded by hyperglycaemia and hyperinsulinaemia. The peak of the mean growth hormone levels occurs at 135 min after initiation of the infusion. In all but one hypopituitary patients the nucleotides do not promote growth hormone secretion. It is concluded that exogenous cyclic 3',5'-adenosine monophosphate and its dibutyryl derivative may not be considered as analogous and that both compounds may contribute to study growth hormone release in normal subjects and in patients with growth abnormalities.     

Effects of hypophysectomy and substitution with growth hormone, prolactin, and thyroxine on growth and deposition in juvenile frogs, Xenopus laevis

Handling and confinement caused a pronounced elevation in the plasma cortisol levels of brown trout. This response was more rapid, and the elevation greater, at 13.4 than at 5 degrees although basal cortisol levels were also higher at the warmer water temperature. The large increase in plasma cortisol caused by handling and confinement was not accompanied by any changes in the plasma levels of either alpha-MSH or endorphin. However, when handling and confinement was combined with a thermal shock, not only was there a rapid and pronounced elevation in plasma cortisol, but there were also concomitant and sustained rises in the plasma levels of both alpha-MSH and endorphin. The levels of a alpha-MSH and endorphin induced by the thermal shock were considerably higher than those recorded in long-term, black-adapted brown trout, the only other circumstance in fish known to cause an elevation of the plasma levels of these two peptides. These results indicate that handling and confinement only activated the corticotrophs of the pars distalis, not the melanotrophs of the neurointermediate lobe, whereas when combined with a thermal shock, both cell types were activated.     

Effect of changes in plasma levels of free fatty acids on plasma glucagon,insulin, and growth hormone in man

A regulatory role of acute changes in plasma concentration of free fatty acids on glucagon secretion has been suggested. We have studied the effect of such changes on plasma levels of glucagon, insulin, and growth hormone in man. Basal plasma levels of immunoreactive glucagon (IRG) were only slightly raised in 11 healthy subjects when the mean concentration of free fatty acids (FFA) was depressed to levels as low as 0.315 ± 0.043 (SEM) mM by infusion of nicotinic acid. Basal levels were increased modestly when the mean FFA level was elevated to 3.027 ± 0.184 mM by infusion of a triglyceride emulsion (Intralipid) with heparin. The plasma IRG response to intravenous arginine was unaffected by high or low levels of plasma FFA. These findings contrasted with the effects upon plasma levels of immunoreactive insulin (IRI) and growth hormone (IGH). During elevation of FFA levels, the mean basal level of plasma IRI increased by 100%, and the IRI response to arginine increased by 50%. Concomitantly, basal IGH levels and the plasma IGH response to arginine were suppressed markedly by elevation of FFA levels. The results of these studies do not offer support for a significant role of variation in plasma level of FFA as a regulator of acute changes in plasma IRG in man. An influence of changing levels of FFA on insulin secretion was found, and an effect on levels of growth hormone was confirmed.     

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.     

Growth hormone release in unstable diabetes: Tests with saline,arginine, glucagon,and epinephrine

Summary Changes in plasma growth hormone (HGH) concentrations during tests with arginine, glucagon, epinephrine and saline were compared in 8 unstable and 4 stable diabetics, and 5 normal subjects. These same subjects had previously also been tested with insulin-induced hypoglycemia and their blood glucose variability had been quantified during near-normal (ambulatory-fed) living conditions. Compared with saline infusion, arginine induced higher HGH increases but glucagon and epinephrine did not. Compared to preinfusion levels, epinephrine decreased HGH concentrations. Patterns of mean HGH increase and decrease after arginine were similar in the 3 groups of subjects. Only during saline infusion did unstable diabetics have higher peak levels than did stable diabetics and normal subjects. The higher or similar increases of HGH in unstable diabetics always occurred at higher concentrations of blood glucose and frequently, but not invariably, at higher concentrations of serum free fatty acids and ketone bodies than in stable diabetics and in normals. HGH release is abnormal in unstable diabetics in that hyperglycemia does not inhibit the release of HGH. The abnormality is associated with impaired modulation of blood glucose and other variables through inability to secrete endogenous insulin. Traduzione a cura degli AA.     

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.     

Response of plasma ACTH and adrenocortical hormones to potassium loading in essential hypertension

The effect of potassium loading on plasma adrenocortical hormones concentrations in 9 patients with essential hypertension (EH) was investigated. The plasma renin activity (PRA), plasma concentrations of growth hormone (GH), ACTH, cortisol, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC) and aldosterone, and serum electrolytes were measured before and after potassium chloride (KC1) infusion (0.33 mEq/kg/h, for one hour). The KC1 infusion caused significant increases in serum potassium levels and plasma levels of GH, ACTH, cortisol, DOC, 18-OH-DOC and aldosterone, while PRA remained unchanged. Regression analysis at 30 min revealed significant positive correlations between delta ACTH and delta cortisol, between delta ACTH and delta DOC, between delta ACTH and delta 18-OH-DOC. However, the relationship between delta ACTH and delta aldosterone was not statistically significant. These results suggest that (1) acute potassium loading causes a significant increase in the plasma ACTH level and increased levels of adrenocortical hormones may be produced by increased ACTH secretion, and (2) it may be considered that a part of the increased level of plasma aldosterone following acute potassium loading may arise from increased ACTH secretion in EH.     

17 alpha-hydroxylase deficiency: mineralocorticoid hormone profiles in an affected family

The plasma concentrations of mineralocorticoid hormones, basal and after stimulation and suppression with ACTH, can identify the heterozygotes in a family with two siblings with 17 alpha-hydroxylase deficiency. Both parents and one sibling had elevated levels of plasma deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycorticosterone, but normal cortisol and aldosterone concentrations. Stimulation with ACTH effected additional increases in the elevated steroid and cortisol levels, but not in aldosterone, further increasing the discrepancy and the ratio between 18-hydroxycorticosterone and aldosterone. One sibling had normal steroid patterns and an 18-hydroxycorticosterone to aldosterone ratio. Suppression of ACTH restored the steroids to low normal levels. In addition, the ratio of the gas chromatographic analysis of the total major urinary metabolites of corticosterone to total metabolites of cortisol was greater, and the sum of urinary androsterone and etiocholanolone to total corticosterone and cortisol metabolites was less in the heterozygotes than in normal subjects. This identifies deficient 17-hydroxylation, which is required for the production of cortisol and C-19 steroids. These criteria appear unique for the 17 alpha-hydroxylase defect in the heterozygote.     

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.     

Pituitary proopiomelanocortin-derived peptides and hypothalamus-pituitary-interrenal axis activity in gilthead sea bream (Sparus aurata) during prolonged crowding stress: differential regulation of adrenocorticotropin hormone and alpha-melanocyte-stimulating hormone release by corticotropin-releasing hormone and thyrotropin-releasing hormone

Plasma levels of cortisol, growth hormone (GH), adrenocorticotropin hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), N-acetyl-beta-endorphin, in vitro ACTH-stimulated cortisol secretion, and in vitro corticotropin-releasing hormone (CRH)- and thyrotropin-releasing hormone (TRH)-stimulated ACTH and alpha-MSH secretion were investigated in gilthead sea bream exposed to high stocking density (30 kg m(-3)) for 23 days. Within 3 days after the onset of crowding, plasma levels of cortisol, ACTH, alpha-MSH, and N-acetyl-beta-endorphin were above control values. After 7 days, plasma parameters had returned to control levels, but at 23 days, cortisol, alpha-MSH, and N-acetyl-beta-endorphin levels were again elevated over controls, indicating a long-term activation of the melanotrope cells. In contrast, crowding stress elicited a prolonged reduction in plasma GH levels concomitant with the increased hypothalamus-pituitary-interrenal axis (HPI) activation. Crowding stress enhanced cortisol secretory activity of the unstimulated interrenal cells. However, interrenal tissue from crowded fish in vitro displayed an attenuated response to ACTH stimulation compared with tissue from control fish, indicating a desensitization of these cells to ACTH during crowding. The involvement of pituitary proopiomelanocortin-derived peptides in the HPI axis of sea bream is indicated by the observed modulation of the CRH and TRH responsiveness of the corticotropes and melanotropes in crowded fish. At day 1, when there were crowding-induced plasma increases in ACTH and alpha-MSH, there was an attenuated CRH-stimulated but not TRH-stimulated, ACTH release. However, at that time, CRH- and TRH-induced responses of alpha-MSH secretion, and the unstimulated secretory activity of the MSH cells, were enhanced in crowded sea bream. These data provide evidence for stimulatory roles of multiple hypothalamic (CRH and TRH) and pituitary (ACTH and alpha-MSH) peptides in the activation of the hypothalamus-pituitary-interrenal axis under crowding conditions in sea bream.     

Effects of acute and chronic stress on the levels of circulating growth hormone in the rainbow trout, Oncorhynchus mykiss.

The acute stress of handling followed by confinement for a period of 1 or 24 hr caused a typical stress response in rainbow trout (elevation of plasma ACTH and cortisol) and a significant reduction in the concentration of circulating growth hormone. The chronic stress of low oxygen levels in both crowded and uncrowded tanks of fish caused a significant elevation of circulating GH levels, an effect which was abolished by the provision of additional aeration to the rearing tanks. This chronic elevation of GH levels was closely correlated with an elevation of plasma cortisol in the same fish. These findings are discussed in relation to stress-induced growth suppression and to the links between the hypothalamic-pituitary-interrenal axis and somatotrope activity.     

The effect of alanine infusions on growth hormone,insulin, and glucose in protein-calorie malnutrition

In view of the previously reported inverse correlation between the elevated serum growth hormone (HGH) and low alanine in children with protein-calorie malnutrition (PCM), 30-min alanine infusions were performed in five children with PCM and 12-hr infusions in four children before and after therapy. These infusions did not lower basal HGH or improve its glucose suppressibility in untreated PCM, excluding a feedback relationship between HGH and alanine. There was no insulinotropic effect during 30-min infusions, but an improved insulin response to glucose after the 12-hr alanine infusion was found in three of four children before therapy. Plasma glucose rose slightly during alanine infusion in three of five children before treatment, but the magnitude of change was small and the relevance unclear.     

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.     

Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children.

The interaction between the immune and endocrine systems has recently been investigated. Hodgkin's disease represents a model of immune disturbance frequently associated with endocrine impairment. The present study evaluated the effect of the acute administration of beta-interferon or thymopentin on plasma growth hormone, prolactin and cortisol levels in children with Hodgkin's disease (N = 8) and age- and sex-matched healthy controls (N = 8). beta-interferon (1,000,000 IU), thymopentin (50 mg) or placebo (saline) were injected after two basal blood samples (-15 and 0) and further samples were drawn at 15, 30, 45, 60, 90 and 120 min. Plasma growth hormone, prolactin and cortisol levels were measured by specific RIAs. Plasma prolactin levels did not show significant change following beta-interferon or thymopentin injection in either the controls or the patients. In the patients with Hodgkin's disease, beta-interferon injection induced a significant increase in both plasma growth hormone and cortisol levels, while thymopentin was not effective. In controls both thymopentin and beta-interferon administration increased plasma growth hormone and cortisol levels. These results indicate that beta-interferon and thymopentin are immune substances active on the release of growth hormone and cortisol in healthy children. The lack of effect of thymopentin in children with Hodgkin's disease suggests an impairment of the immune-endocrine interaction in these patients.     

Dopaminergic Modulation of Corticosteroid Responses to Angiotensin II in Man

This study was designed to investigate dopaminergic mechanisms involved in the control of corticosteroid secretion in man. Plasma cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone (18-OHB), and aldosterone responses to graded doses of angiotensin II and ACTH were evaluated in six healthy male volunteers with and without treatment with the dopamine agonist bromocriptine (BEC). Angiotensin II infusion resulted in parallel responses of 18-OHB and aldosterone without affecting other precursors of the aldosterone biosynthetic pathway. BEC (2.5 mg tid for 6 days) markedly suppressed basal supine plasma 18-OHB levels without affecting basal levels of aldosterone. Basal supine plasma corticosterone levels were increased after BEC treatment. BEC treatment inhibited the 18-OHB and aldosterone responses to graded infusions of angiotensin II. Plasma 18-OHB responses to ACTH infusion were not altered by BEC treatment. Other factors known to affect aldosterone and 18-OHB secretion such as plasma renin activity and serum electrolytes were not altered by BEC administration. These results suggest that angiotensin-mediated 18-OHB and aldosterone secretion is selectively inhibited by dopaminergic mechanisms.