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Biomedical subjects

A Grossman

Publications and source records attributed to A Grossman.

At least 217 records · Page 12Linked to original sources
PubMed1986

The interaction of growth hormone releasing hormone with other hypothalamic hormones on the release of anterior pituitary hormones.

To determine whether the 29 amino-acid fragment of growth hormone releasing hormone (GHRH) can be combined with other hypothalamic releasing hormones in a single test of anterior pituitary reserve, the responses of anterior pituitary hormones to combinations of an i.v. bolus of GHRH(1-29)NH2 or saline with an i.v. bolus of either LH releasing hormone (LHRH) plus TRH, ovine CRH(oCRH) or saline were studied. Each infusion of GHRH(1-29)NH2 resulted in a rapid increment of the plasma GH value. Infusion of GHRH(1-29)NH2 also caused a small and transient rise in plasma PRL, but no change in the integrated PRL response. The combination of GHRH(1-29)NH2 with LHRH plus TRH caused a larger increment of peak and integrated plasma TSH levels than LHRH plus TRH alone. GHRH(1-29)NH2 did not affect the release of other anterior pituitary hormones after infusion with oCRH or LHRH plus TRH. Because of the finding of potentiation of the TSH-releasing activity of LHRH plus TRH by GHRH(1-29)NH2, the study was extended to the investigation of TSH release after infusion of TRH in combination with either GHRH(1-29)NH2 or GHRH(1-40). In this study the combination of TRH with both GHRH preparations also caused a larger increment of the peak and integrated plasma TSH levels than TRH alone. It is concluded that GHRH(1-29)NH2 possesses moderate PRL-releasing activity apart from GH-releasing activity. In addition, GHRH potentiates the TSH-releasing activity of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Depot-bromocriptine treatment for prolactinomas and acromegaly.

Fifteen patients with hyperprolactinaemia and pituitary macroadenomas (5 patients), microadenomas (6 patients), or acromegaly (4 patients) were given a single intramuscular injection of 50 mg bromocriptine bound to polylactic acid microspheres, depot-bromocriptine. None of the patients had any short-term or long-term discomfort from the injection. In the 11 patients with prolactinomas, serum prolactin fell to minimum levels 12-72 h post-injection; nine patients were highly responsive to depot-bromocriptine, with a mean serum prolactin of 12.9% of basal levels 24 h post-injection, rising to 19% at 28 days. Two patients with prolactinomas were resistant to both depot-bromocriptine, and large doses of oral dopamine agonists. Initiating side-effects (nausea, vomiting, symptomatic postural hypotension) were seen in five patients in the first 24 h post-injection, but were minimal or absent thereafter. Five of six patients previously intolerant of oral dopamine agonists were able to be transferred successfully to bromocriptine 5 mg daily at 4 weeks. Of the four patients with acromegaly, raised prolactin levels were successfully lowered to normal for 4 weeks after injection; serum GH was also partially lowered, but returned to baseline levels at 2-4 weeks. In one patient serum GH was resistant to suppression by both depot bromocriptine and high doses of oral bromocriptine. One patient with a large tumour and visual field defects showed a rapid and maintained improvement in visual fields and acuity after depot-bromocriptine, and was successfully transferred to high-dose oral bromocriptine at 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1986

Normal circulating immunoreactive growth hormone releasing factor (hGRF) concentrations in patients with functional hypothalamic hGRF deficiency.

Using a highly specific radioimmunoassay we have measured the concentrations of human growth hormone releasing factor (ir-hGRF) in the peripheral circulation of six individuals with acquired hypothalamic hGRF deficiency. Despite their hypothalamic dysfunction venous plasma ir-hGRF increased normally in every patient after the stimulus of a mixed breakfast, from an average concentration basally of 13.6 +/- 6.0 pg/ml to a maximum of 29.0 +/- 8.4 pg/ml (mean +/- SEM) at 120 min. The findings indicate that circulating hGRF is at least in large part extrahypothalamic in origin, which in turn implies a physiological role for hGRF in the periphery.

Adolescent↗
PubMed1986

An analogue of met-enkephalin attenuates the pituitary-adrenal response to ovine corticotrophin releasing factor.

The met-enkephalin analogue, DAMME, suppresses the pituitary-adrenal axis in normal subjects; it is not clear whether this occurs at the level of the pituitary or above. We therefore administered synthetic ovine corticotrophin releasing factor (CRF-41) 100 micrograms i.v. to a group of normal male subjects, with or without pretreatment with DAMME 250 micrograms i.v., and monitored the response of plasma ACTH and serum cortisol. CRF-41 caused a marked stimulation of ACTH and cortisol release, but this was significantly attenuated by pretreatment with DAMME. It is therefore concluded that DAMME either directly inhibits the corticotroph at the level of the pituitary, or that it suppresses release of an additional factor which normally potentiates the action of CRF-41 on the pituitary.

Adolescent↗
PubMed1986

Naloxone provokes catecholamine release in phaeochromocytomas and paragangliomas.

The effects of low- (2 mg) and high-dose (10 mg) intravenous naloxone administration on circulating plasma catecholamines in four patients with proven and two patients with suspected phaeochromocytomas have been evaluated. In three out of four patients with confirmed phaeochromocytomas or paragangliomas, 10 mg naloxone resulted in a marked rise (290-575%) in circulating noradrenaline; despite combined alpha and beta-adrenoceptor blockade, in two out of four cases systolic and diastolic pressures rose whilst pulse rate fell. No response was seen to 2 mg naloxone in any patient. No humoral or pressor response was obtained in the fourth patient, who may have been secreting maximal levels of plasma noradrenaline at the time of study. In the two patients with suspected phaeochromocytoma, there was no response to naloxone: further investigations failed to reveal a source of abnormal catecholamine secretion in these patients. It is concluded that naloxone represents a new pharmacological agent which can provoke catecholamine release in patients with phaeochromocytomas; in such patients, endogenous opioids may regulate catecholamine release either from the tumour itself or from the enhanced peripheral catecholamine stores.

Adolescent↗
PubMed1986

Different opioid mechanisms are involved in the modulation of ACTH and gonadotrophin release in man.

Both the pituitary-adrenal axis and the pituitary-gonadal axis are under the tonic inhibitory control of endogenous opioid peptides in man. However, the precise opioid receptor involved in the modulation of these hormones remains unknown. The effect of a dose of intravenous naloxone on serum levels of luteinising hormone (LH), follicle-stimulating hormone (FSH) and plasma cortisol was therefore investigated in ten normal subjects. In the male subjects, naloxone at a dose of 25 micrograms/kg caused a significant increase in serum LH and FSH; no increase in response was seen at the two higher doses (100 micrograms/kg and 250 micrograms/kg). The lowest dose (6 micrograms/kg) caused no change in serum LH and FSH. In the female subjects, tested in the early follicular phase of their cycles, no dose of naloxone significantly increased circulating gonadotrophins. In both male and female subjects, naloxone only stimulated a rise in serum cortisol at the highest dose (250 micrograms/kg). A second study in six normal subjects demonstrated that the rise in cortisol with the highest dose of naloxone was secondary to a rise in plasma ACTH. It is concluded that the opioid receptor(s) controlling gonadotrophin release in man are naloxone-sensitive, and are probably epsilon-receptors; the naloxone insensitivity of the pituitary-adrenal axis suggests that these responses are modulated by kappa- or delta-receptors.

Adrenocorticotropic Hormone↗
PubMed1986

Effect of adrenergic antagonism on the growth hormone, prolactin and cortisol response to a synthetic opioid agonist in man.

The intravenous administration of 250 micrograms D-Ala2-MePhe4-Met-enkephalin-O-ol (DAMME) caused a marked increase in circulating growth hormone (GH) and prolactin (PRL), and a fall in cortisol, in 14 normal subjects. Neither the alpha 1-antagonist thymoxamine, nor the alpha 2-antagonist yohimbine, significantly altered the GH and PRL responses to DAMME, suggesting that in man the growth hormone- and prolactin-releasing effects of exogenous opioids are not mediated through adrenoceptor pathways. The fall in cortisol induced by DAMME was not affected by thymoxamine, but was significantly attenuated by yohimbine, indicating that opioids may lower circulating cortisol via an interaction with noradrenergic pathways.

Adult↗
PubMed1986

Steroids and the secretory function of the exocrine pancreas.

The influence of steroids on the exocrine pancreas of male rats was examined by removing steroid producing tissue and by introducing individual steroids into these animals at a later date. Castration had no demonstrable morphological effect on acinar cells, whereas castration combined with adrenalectomy caused a marked depletion of zymogen granules as well as widening of peri- and interlobular spaces. Treatment of castrated-adrenalectomized rats with estradiol restored a normal appearance of the pancreas within about 9 h. Triamcinolone acetonide produced similar results. These morphological changes were accompanied by significant alterations of the relative amounts of digestive enzymes present in zymogen granules. A marked reduction of amylase occurred in the castrated-adrenalectomized group. Neither estradiol nor triamcinolone could reverse these effects within 9 h. Castration alone had no significant effect on the relative proportion of amylase; however, it increased the relative amount of proteases. This effect was reversed by estradiol treatment. Estradiol also induced significant changes in the proportion of proelastase in castrated-adrenalectomized animals. Replacement therapy in castrated-adrenalectomized rats with dexamethasone or triamcinolone partially restored the level of amylase in the pancreas, whereas estradiol did not cause any significant effect. At the ultrastructural level, castration and adrenalectomy caused swelling of the Golgi apparatus and accumulation of condensing vacuoles. These effects were reversed by either estradiol or triamcinolone. Also, after acute treatment of these animals with estradiol, two unusual features of acini were noted. In some acini, a type of granule that we termed halo granule appeared. These halo granules were either distinctly separated organelles or formed composite structures that did not appear to be associated with the luminal membrane. Freeze-fracture studies revealed that secretory vesicles in apparently normal acini adhered to each other at specific contact sites characterized by aggregates of intramembrane particles. Multiple sites of contact could be seen in the same vesicle. From our observations it is clear that steroids from the testes and adrenals exert major effects on the secretory apparatus of pancreas; more specifically on the mechanisms that determine the proportions of the different digestive enzyme and on their packaging in the zymogen granules.

Adrenalectomy↗
PubMed1986

Effect of an opiate antagonist on the responses of circulating catecholamines and the renin-aldosterone system to acute sympathetic stimulation by hand-grip in man.

The effect of naloxone on the neurohumoral responses to acute sympathetic stimulation by sustained hand-grip in normal man was investigated. Six normal males were studied fasting at 08.30 h, on two occasions at 7-day intervals, with each subject sustaining 30% of his maximal hand-grip on a hand dynamometer for 5 min. Naloxone (8 mg bolus) in 20 ml normal saline, or saline alone, was given 5 min before hand-grip in a randomised double-blind cross-over trial. Blood was sampled for plasma renin activity, serum aldosterone and plasma catecholamines. The study was repeated in the absence of hand-grip. Sustained hand-grip produced significant elevations in mean blood-pressure, circulating adrenaline, noradrenaline and aldosterone. Naloxone, which had no effect on basal catecholamines, plasma renin activity or aldosterone, significantly enhanced the responses in plasma adrenaline, plasma renin activity and serum aldosterone to hand-grip. The increments in blood pressure and noradrenaline were not affected. These results suggest that endogenous opioids modulate the response of the sympathoadrenal and renin-aldosterone systems to acute sympathetic stimulation by a mild stress in man.

Adult↗
PubMed1986

Growth hormone-releasing hormone in the diagnosis and treatment of growth hormone deficient children.

A growth hormone-releasing hormone (GHRH) has recently been extracted and synthesised, and appears to be identical to human hypothalamic GHRH. Immunoreactive GHRH is found in the venous blood of normal subjects and GH-deficient children, but is probably not hypothalamic in origin and therefore not important in GH regulation. GHRH is a potent specific stimulator of GH secretion in man, and provides a valuable diagnostic test in differentiating hypothalamic from pituitary causes of GH deficiency. Preliminary data suggests that GHRH may promote linear growth in some GH deficient children. GHRH may well prove an important alternative therapy for GH deficient children especially if depot preparations or intranasal administration prove effective.

Child↗
PubMed1986

Cranial irradiation for cerebral and nasopharyngeal tumours in children: evidence for the production of a hypothalamic defect in growth hormone release.

A synthetic 29-amino acid analogue of human pancreatic GH-releasing hormone (GHRH(1-29)NH2) has recently been shown to stimulate the release of GH in normal subjects. We have studied the GH response to GHRH(1-29)NH2 in nine children irradiated for brain and nasopharyngeal tumours, who were not growing and were deficient in GH as assessed by insulin-induced hypoglycaemia. Serum GH rose in response to GHRH(1-29)NH2 in all the children, and in five the peak serum GH response was greater than 20 mu./l. The data suggest that when hypothalamo-pituitary irradiation results in GH deficiency, this is due to a failure of the synthesis or delivery of endogenous GHRH from the hypothalamus to the pituitary cells. It also suggests that it may be possible to treat such children using synthetic GHRH in place of exogenous GH.

Body Height↗
PubMed1985

Effect of liver and renal dysfunction on circulating methionine-enkephalin immunoreactivity.

Plasma methionine-enkephalin (Met-Enk) immunoreactivity has been determined in 24 patients with varying degrees of renal impairment and 14 patients with hepatic failure. Plasma Met-Enk immunoreactivity correlated inversely with creatinine clearance (r = -0.71, P less than 0.001) but was not affected by even severe hepatic failure in the absence of renal impairment. In two patients, with renal failure and elevated plasma prolactin, administration of naloxone (16 mg) had no effect on circulating prolactin concentrations. These studies indicate that the kidney has a major role in Met-Enk metabolism while the liver does not, and further suggest that elevated circulating endogenous opiates are not responsible for the increased production of prolactin found in renal failure.

Enkephalin, Methionine↗
PubMed1985

Effect of histamine infusion on circulating methionine-enkephalin and catecholamine concentrations.

In 5 normal adult men, histamine was infused i.v. for 5 min at 20 micrograms/kg/h and at 80 micrograms/kg/h on two occasions one week apart. Diastolic blood pressure fell and heart rate, plasma adrenaline and noradrenaline all rose in a dose-dependent manner, but plasma methionine-enkephalin (Met-Enk) concentrations were unchanged. These results indicate that while Met-Enk may be co-stored with catecholamines (CAs) in the adrenal medulla in at least this paradigm, circulating concentrations of CAs may be altered without similar changes in plasma Met-Enk immunoreactivity.

Adrenal Medulla↗
PubMed1985

Prolactinomas.

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Bromocriptine↗
PubMed1985

The CRFs and their control: chemistry, physiology and clinical implications.

The 41-amino acid CRF fulfils all the criteria for a corticotrophin releasing factor, although considerable evidence suggests that other factors, particularly VP, also play a physiologically significant role in controlling ACTH release. Although human CRF has now been identified as a 41-residue peptide, most studies to date have used oCRF-41 in their exploration of the physiology and pathology of the hypothalamic--pituitary--adrenal axis. Low doses of oCRF-41 appear to be safe, and for specific tests of the readily-releasable pool of ACTH and related peptides 100 micrograms is a practical dose for most purposes. Although serious side-effects have only been noted at doses above 100 micrograms, it is reasonable to monitor all patients administered CRF-41 with great care, and in particular to be alert to hypotension, especially in patients with corticosteroid deficiency. There is little doubt that, in combination with the standard insulin-tolerance test, the CRF test is a useful means of diagnosing hypothalamic or portal dysfunction in patients with secondary adrenal failure. However, in the diagnosis and differential diagnosis of Cushing's syndrome, the role of the CRF test remains unclear. In normal subjects, a high basal cortisol level usually inhibits the response to CRF, such that a greatly enhanced response is suggestive of pituitary-dependent Cushing's syndrome. In patients with diagnosed ACTH-dependent Cushing's syndrome, an absent response to CRF predisposes towards an ectopic source of ACTH. However, there are exceptions in all directions, and it is uncertain whether the CRF test will prove of greater value than the traditional procedures, such as the dexamethasone suppression test. The differential diagnosis of depression and Cushing's disease may be its greatest value. In terms of treatment, there are as yet few data on the usefulness of CRF in expediting recovery of the pituitary-adrenal axis following long-term suppression, such as in patients with Cushing's syndrome treated by removal of a unilateral adenoma or trans-sphenoidal microadenomectomy. It is possible that such treatment may eventually be a useful application of CRF, although data are not yet available.

Acetylcholine↗
PubMed1985

Enhancement of the sympathoadrenal response to the cold-pressor test by naloxone in man.

The effects of naloxone (8 mg) on the pressor and plasma catecholamine response to a standard cold-pressor test have been evaluated in six normal male subjects. Plasma catecholamines were estimated by high performance liquid chromatography coupled to electrochemical detection. Cold stimulation induced significant elevations in plasma noradrenaline and adrenaline to reach mean peak levels 61% and 108% above their respective basal levels (P less than 0.05). Systolic blood pressure increased by 23 +/- 6.5 mmHg (P less than 0.001), and heart rate increased by 7.5 +/- 2.5 beats/min (P less than 0.001). Naloxone pretreatment significantly enhanced the plasma adrenaline response to the cold stimulus by 98% (P less than 0.01) with concomitant changes in peak systolic blood pressure (peak increment 31 +/- 6 mmHg) and pulse rate (12.5 +/- 3.5 beats/min) responses (both P less than 0.05). The mean plasma noradrenaline response to cold also increased after naloxone, but this failed to achieve significance. Endogenous opioids are likely to be involved in the sympathoadrenal response to a mild acute stress in man.

Adult↗