Growth Hormone In Man Research Articles

Effect of Analogues of Somatostatin on Pancreatic and Gut Hormones and Growth Hormone in Man

Effect of Analogues of Somatostatin on Pancreatic and Gut Hormones and Growth Hormone in Man

Effects of haloperidol on afternoon sleep and on the secretion of growth hormone in man

The sleep pattern and the plasma concentration of growth hormone were determined during afternoon naps of seven healthy young subjects after i.v. treatment with 3.5 mg haloperidol. The latency of sleep onset and the period in stage 2 were reduced, but the time spent awake was increased compared to control conditions. The magnitude of the sleep induced peak in growth hormone concentration was not modified in five subjects. In two subjects it was abolished as a consequence of shortened sleeping time and disturbed sleep. It is suggested that unlike growth hormone secretion induced by endocrine or metabolic factors, that occurring during sleep is not mediated by a central dopaminergic neuronal pathway.

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) m M by infusion of nicotinic acid. Basal levels were increased modestly when the mean FFA level was elevated to 3.027 ± 0.184 m M 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.

Effects of 2-Bromo-Alpha-Ergocryptine on the Secretion of Pituitary Hormones in Normal Male Subjects

It is well known that catecholamines in the hypothalamus influence the control of release of hormones by the anterior pituitary, especially that of prolactin and Gil. Catecholamines are reported to play a role as a neurotransmitter which stimulates the release of prolactin release-inhibiting factor (PIF) and/or directly to inhibit the relase of prolactin at the pituitary gland. L-dopa, the precursor of dopamine, is known to stimulate the secretion of growth hormone in man. On the other hand, although the effects of catecholamines on the release of gonadotropins and ACTH from the pituitary gland were studied by many investigators, the results are inconsistent. McCann and his coworkers reported that the release of gonadotropins was stimulated by dopamine or dopaminergic mechanism. On the contrary, Fuxe found that the dopaminergic neuron took part in inhibiting the release of gonadotropins. On the release of ACTH, the results obtained by Abe and Hiroshige were different from those by Ganong and his coworkers.Recently, the ergot alkaloid, 2-bromo-alpha-ergocryptine (CB-154, Sandoz Co.), was found to be a strong dopaminergic stimulator, to inhibit the secretion of prolactin, and to be effective in inhibiting galactorrhea.In the present study, effects of CB-154 which was used as a strong dopaminergic stimulator on plasma prolactin, LH, FSH, TSH, Gil and ACTH levels in normal male subjects are investigated.After an over-night fast, 2. 5 mg of CB-154 was orally administered 8 a.m. and blood sample was withdrawn 10 a.m. and then 100 μg of luteinizing hormone-releasing hormone (LH-RH) and 500 μg of thyrotropin-releasing hormone (TRH) was injected intravenously. After the injection, 1-arginine (0.5 g/kg b.w.) was infused into a cubital vein over 30 min. Blood was taken 15, 30, 60, 90, and 120 min following the injection of LH-RH and TRH.Plasma ACTH, GH TSH, LH, FSH and prolactin were determined by radioimmunoassay kits.The following results were obtained : 1) CB-154 inhibited not only basal plasma prolactin levels, but also the increase in plasma prolactin levels induced by TRH.2) Although the single administration of CB-154 had no effect on basal plasma LH and FSH levels, the increase in plasma gonadotropins, especially FSH, induced by LH-RH had a tendency to be enhanced by CB-154.3) CB-154 suppressed the increment of plasma TSH by TRH in normal male subjects.4) The oral administration of CB-154 had a tendency to elevate basal plasma GH levels, it did not augment the increase in plasma GH levels induced by 1-arginine.5) In a few case, CB-154 enhanced ACTH release. However, the effect of CB-154 on ACTH release was inconsistent. These results revealed that CB-154, a strong dopaminergic stimuiant, inhibits the release of TSH as well as that of of prolactin in normal male subjects, and stimulates the release of gonadotropins and of GH.

Lack of effect of hyperglycaemia on apomorphine induced growth hormone release in normal man.

Six healthy adult males were studied to evaluate the effect of apomorphine on growth hormone (GH) secretion under normoglycaemic and hyperglycaemic conditions. Both under normoglycaemia and hyperglycaemia all subjects responded to the subcutaneous injection of 0.75 mg apomorphine hydrochloride with a marked increase in plasma GH concentration reaching a maximum after 30-60 min. In control studies no significant changes in plasma GH were observed following the injection of physiological saline. As apomorphine is considered a selective dopamine receptor stimulating agent, the results support the view that GH release in man can be modulated through a dopaminergic mechanism. The finding that the plasma GH rise after the administration of apomorphine is not suppressible by glucose indicates that apomorphine activates dopaminergic receptors localized distally in the hypothalamus or in the anterior pituitary. Amorphine in low dosage may be used clinically to test the capacity of the pituitary to release GH in man, at least in special cases.

Effect of electroconvulsive therapy without anticonvulsive premedication on serum growth hormone in man.

Serum concentrations of human growth hormone (HGH) were measured in psychiatric patients during the first, third and sixth electroconvulsive therapy (ECT) without anticonvulsive premedication. Serum HGH increased 30 min after the application of current and no differences were found between responses to 1st, 3rd, or 6th ECT. Maximal increase of serum glucose was seen after the first ECT and gradual decreases after the 3rd and 6th ECT were observed

Effect of cyproheptadine on human growth hormone secretion.

ABSTRACT In order to determine whether or not a serotonergic mechanism is involved in the secretion of growth hormone, the effect of cyproheptadine, an antiserotonergic agent, on plasma human growth hormone (hGH) levels was studied in normal human subjects. Oral administration of 150 mg of 5-HTP, a precursor of serotonin, caused a rise in plasma hGH in 7 of 8 normal subjects tested, with peak hGH levels of 21.1 ± 4.7 ng/ml (mean ± sem). Plasma hGH response to 5-HTP was significantly suppressed by the intravenous infusion of cyproheptadine, an antiserotonergic agent (p < 0.01). Intravenous infusion of arginine caused a significant increase in plasma hGH, with peak hGH levels of 20.6 ± 4.9 ng/ml (mean ± sem). Plasma hGH response to arginine was significantly suppressed by the intravenous infusion of cyproheptadine (p < 0.05). These results suggest that the serotonergic mechanism is involved in the secretion of growth hormone in man.

Retention of biologic activity of human growth hormone in man after reduction and alkylation.

ABSTRACT This study demonstrates the lipolytic, nitrogen-retaining, calciuric and insulinotropic capacities of reduced tetra-S-carbamidomethyl hGH (RCAM-hGH). hGH was reduced with dithiothreitol and alkylated with iodoacetamide to yield RCAM-hGH. Total reduction was confirmed by quantitative yield of 4 residues of S-carboxymethylcysteine per mole RCAM-hGH. After 8 days on a diet of known composition, 2 prepubertal males with growth hormone deficiency received 5 mg RCAM-hGH im daily for 5 to 6 days. Five to 7 days later, 5 mg hGH im daily, was given for 4 days. RCAM-hGH administration caused an average daily decrease in urinary nitrogen of 39% and increased urinary calcium to 150% of control value. The rise in plasma free fatty acids 4 hr after im injection of RCAM-hGH or of hGH was similar. Intravenous glucose disposal (Kg 1.55) on the 4th day of RCAM-hGH administration was unchanged from the control value. Fasting insulin (IRI) increased from 6 to 21 μU/ml and the area of IRI response to glucose rose to ...

Human Pituitary Growth Hormone.

The modern era of growth hormone in clinical medicine was ushered in by Raben in 1958 when he reported on the successful treatment of a child with pituitary dwarfism with growth hormone. Prior to that time, the history of human growth hormone had been chequered with misunderstandings and doubts were even expressed that a human growth hormone existed. Extracts of most animal pituitaries were without effect on man and until the nature of the species specifity of growth hormone was unraveled the dilemma of apparent inactivity of growth hormone in man remained frustrating. In the late 1950s when it was learned that only growth hormone from human and anthropoid sources were effective in man, a new age of understanding began. This was followed in rapid sequence by perfection of the radio-immunoassay technique for growth hormone, determination of the aminoacid sequence of the molecule, formation of the National Pituitary Agency to

Some metabolic changes induced by acute administration of native and reduced-tetra-S-carbamidomethylated human growth hormone in man.

Reduction and carbamidomthylation of the disulfide bridges of HGH was followed by a 50% decrease of the immunological activity of the hormone. This indicates that the immunological activity of the HGH molecule is dependent upon the disulfide bridges. The effects of HGH in man on glucose in blood and glycerol, alamine and insulin in plasma, as well as on glucose tolerance and insulin response to glucose, were not altered by the reduction of the molecule. Thus, there seems to exist a dissociation of the sites of the molecule which are responsible for the biological and immunological properties of the hormone. Both native HGH and its reduced derivative, when infused for 1 hr, inhibited partially the insulin response to glucose administration. On prolonged administration, both preparations had an enhancing effect on glucose-induced insulin release. It is suggested that HGH initially suppresses insulin-release, thereby acting as a stress hormone in a similar fashion as the catecholamines. The later enhancement...

The importance of ‘distribution’ in the metabolism of growth hormone in man

The importance of ‘distribution’ in the metabolism of growth hormone in man

Plasma growth hormone concentrations in sheep measured by radioimmunoassay.

SUMMARY Plasma growth hormone (GH) concentrations in adult sheep and lambs were measured by radioimmunoassay. Mean values before feeding were 3·1 (s.e. − 0·4, + 0·5) ng./ml. in lactating ewes and 3·9 (− 0·5, + 0·7) ng./ml. in their lambs. In adult wethers the mean GH concentration before feeding was 2·3 (−0·2, + 0·3) ng./ml. After one i.v. injection of 400 μg. ovine GH, the hormone disappeared from the plasma of adult sheep with a half-time of 7–8 min. Plasma GH concentrations decreased at a similar rate after the establishment of high concentrations of endogenously secreted GH. The results suggest a shorter half-life than has been reported for human GH in man. GH could not be recovered in an immunologically recognizable form in urine. Fasting for 4 days led to no systematic change in plasma GH concentrations. Feeding did not increase plasma GH. Intravenous injection of saline resulted in some increase in plasma GH in both ewes and lambs. In adult sheep intravenous glucose (0·25 g./kg.) did not cause any greater change than that seen after saline, but in lambs an increase occurred. Intravenous injection of insulin (0·25 unit/kg.) resulted in an increase in plasma GH at 15–30 min. and this effect was found in both lambs and ewes. Infusion of adrenaline at either 25 μg. or 50 μg./min. into adult wethers (average body wt 51 kg.) caused a decrease in plasma GH concentration. It was concluded that the changes in plasma GH concentration of sheep in a number of physiological situations differ from those reported to occur in man.

Disappearance rate of endogenous and exogenous human growth hormone in man.

Following hypophysectomy the t1/2 of endogenous HGH in an acromegalic giant (R.C.) was 50 min. HGH fell from a preoperative level of 100 ng/ml to <1 ng/ml 5 days later. In the same patient, the half-times of exogenous Raben HGH administered as a single bolus (275 and 200 μg) were 25.7 and 26.9 min (2 and 9 months post hypophysectomy) and were similar to values reported by others. The t1/2 of HGH in 2 patients with long-standing panhypopituitarism were 15.3 and 14.4 min. In view of the discrepancy observed between the t1/2 of endogenous and exogenous HGH, R.C. was given a 90-min infusion of HGH (4 μg/min), following which the t1/2 was 51.4 min. The distribution space of HGH ranged from 5.2 to 11.2% body wt, and in patient R.C. was similar when estimated from the single bolus or continuous infusion technique (5.2 and 5.7% body wt, respectively). The metabolic clearance rate was 80 ml/min, which approximates that of human placental lactogen obtained by the same technique. It was concluded that (a) the single bolus technique may not be valid for estimating t1/2 of polypeptide hormones that turn over rapidly; (b) the turnover rate of HGH may be slower than previously suggested; (c) exogenous and endogenous HGH have identical half-times when time is allowed for the former to equilibrate; (d) the slow clearance rate of HGH in the acromegalic patient raises the possibility that alterations in the degradation process in pathological conditions may influence the concentration of the hormone in plasma; (e) in the absence of knowledge of the clearance rate, caution must always be used in accepting a serum concentration as being indicative of a secretion rate.

Effect of glucocorticoids on plasma growth hormone in man

Serial plasma growth hormone (GH) values in four normal women were found to fluctuate widely during the day with peak values as high as 32 mμg/ml. The present study established two points: (1) patients with Cushing's syndrome lack normal spontaneous peaks in plasma GH and (2) normal subjects treated for two weeks with prednisone in doses of 15 mg. per day (roughly equivalent to the amount of cortisol secreted in Cushing's syndrome) showed no significant diminution in their spontaneous plasma GH peaks. It is possible that the chronicity, the constancy, and the severity of glucocorticoid excess might all be factors in abolishing the plasma GH peaks in Cushing's syndrome.

Effects of convulsive electroshock on serum concentrations of follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone and growth hormone in man,.

ABSTRACT Serum concentrations of FSH, LH, TSH and GH were measured in men and postmenopausal women who received convulsive electroshock (ECT). Significant increases in serum FSH and LH were noted in some but not all men. No significant increase in serum FSH or LH was noted in postmenopausal women. Greater responses were seen after the third or sixth shock treatment than after the first or sixteenth treatment. ECT had no significant effect on serum TSH concentrations or on GH concentrations in fed subjects.

Metabolic clearance rate of radioiodinated human growth hormone in man.

The nature of the disappearance of radioiodinated human growth hormone (HGH) from plasma has been reexamined. The metabolic clearance rate (MCR) was determined both from single injection and constant infusion studies. After single injection of highly purified radioiodinated HGH, the disappearance curve remained multiexponential during the period of study (4 hr). The shape of the curve was independent of the growth hormone preparation used. Similar disappearance curves were obtained with unlabeled HGH.MCR values calculated from constant infusion studies were 203 +/-7.8 liters/day per m(2) and values derived from single injection studies agreed closely with this. The multiexponential nature of the disappearance curve does not permit meaningful calculation of volume of distribution or half-time of disappearance.

Prolactin

This chapter discusses animal and human prolactin. It describes the chemistry and physiology of animal prolactin and includes a brief survey and critical comparison of the various methods employed for the assay of this hormone. The question of the relationship between prolactin and growth hormone in man is examined, methods of extraction from blood and urine are reviewed, and the data currently available concerning the distribution of this hormone in the human body is reported and discussed in the chapter. The initiation and maintenance of lactation is one of the most characteristic actions of prolactin. Prolactin plays a leading role in mammary growth. In addition, a number of other hormones are involved for this function—growth hormone, the ovarian hormones, thyroxine, and insulin. Prolactin and growth hormone together suffice, even in the absence of the ovarian and adrenocortical hormones, to induce mammary growth in the rat.

Comparison of the effect of the pyrogens, etiocholanolone and bacterial endotoxin on plasma cortisol and growth hormone in man.

We have compared the effects of 2 different bacterial pyrogens with those of the steroidal pyrogen, etiocholanolone, in normal subjects. Lipexal and Piromen produced essentially equal febrile responses and increments in plasma cortisol levels. Piromen evoked significantly greater plasma growth hormone responses than did Lipexal. Although etiocholanolone caused higher and more prolonged fever and more severe constitutional symptoms, plasma cortisol responses were minimal and remained within the normal range, and plasma growth hormone levels did not vary from control values. Thus, fever and the associated nonspecific “stress” do not appear to be important stimuli for the release of ACTH and growth hormone.

Effect of feeding vs. fasting on metabolic changes produced by human growth hormone in man.

ABSTRACT Repeated determinations were made of venous blood levels of fat and carbohydrate intermediary metabolites in 10 normal subjects fasted for 42 hours, given multiple 2-hr feedings of carbohydrate and fat, and following a single im injection of human growth hormone during fasting and during feeding. Fasting produced no significant changes in the levels of blood glucose and lactate; blood pyruvate, citrate, free fatty acids and ketones increased. Blood urea nitrogen decreased initially but subsequently rose above the control. Feeding produced no significant change in 2-hr postprandial levels of carbohydrate and fat metabolites; blood urea nitrogen steadily decreased. Human growth hormone administered during fasting produced a greater rise in free fatty acids and ketones than that observed during fasting alone, and inhibited the late rise in blood urea nitrogen. Human growth hormone markedly altered the response to multiple feedings by producing a marked rise in 2-hr postprandial levels of glucose, py...

SODIUM RETENTION WITH HUMAN GROWTH HORMONE AND ITS SUBFRACTIONS*†

The administration of 10 mg. of human growth hormone within four hours produced a mean retention of approximately 30 mEq. of sodium and potassium per twenty-four hours in 3 of 5 normal subjects receiving a constant dietary intake; there was no change in urinary aldosterone. In 2 there was slight retention—without the rise in aldosterone that was found in a more prolonged study. Urinary sodium decreased after administration of human growth hormone in 2 patients with primary aldosteronism who had been refractory to daily intramuscular injections of 20 mg. of desoxycorticosterone acetate for four days. The magnitude of sodium retention was increased in primary aldosteronism, possibly because of the potassium-depleted state. Sodium retention was also observed in a bilaterally adrenalectomized subject after human growth hormone was administered. Results indicate that sodium retention with human growth hormone in man is independent of aldosterone secretion.