D.H. Coy

Inhibition of gastrin and gastric-acid secretion by growth-hormone release-inhibiting hormone

Abstract The hypothalamic polypeptide growth-hormone release-inhibiting hormone (G.H.-R.I.H.) inhibited gastrin release in all subjects studied. In normal subjects and in patients with acromegaly during a standard food stimulus a G.H.- R.I.H. infusion completely suppressed gastrin release, and immediately after the infusion was stopped gastrin levels rose sharply to exceed control values. Two patients with pernicious anaemia demonstrated a rapid fall in plasma-gastrin during G.H.-R.I.H. infusion, and in a patient with Zollinger-Ellison syndrome a 20-minute G.H.-R.I.H. infusion greatly lowered plasma-gastrin concentrations and almost totally suppressed gastric-acid production.

ACTION OF GROWTH-HORMONE-RELEASE INHIBITORY HORMONE IN HEALTHY MEN AND IN ACROMEGALY

Abstract The synthetic growth-hormone-release inhibitory hormone (G.R.-I.H.) inhibits G.H. response to insulin-induced hypoglycaemia without affecting the prolactin or corticosteroid responses, but the effects are short-lived. The normal thyrotrophin and follicle-stimulating hormone (F.S.H.) responses to thyrotrophin-releasing hormone (T.R.H.) were impaired by G.R.-I.H., although the prolactin response was unaffected. G.R.-I.H. did not alter luteinising hormone (L.H.) or F.S.H basally or after L.H/F.S.H releasing hormone. Circulating G.H. levels fell strikingly in three acromegalic patients given G.R.-I.H. infusion, but their prolactin levels were not affected. G.R.-I.H. holds great promise for the medical treatment of diseases associated with excess G.H. secretion such as acromegaly, gigantism, and diabetes mellitus.

NEW HYPOTHALAMIC HORMONE, CORTICOTROPIN-RELEASING FACTOR, SPECIFICALLY STIMULATES THE RELEASE OF ADRENOCORTICOTROPIC HORMONE AND CORTISOL IN MAN

Abstract A synthetic preparation of the 41-aminoacid-residue peptide recently isolated from ovine hypothalami and characterised corticotropin-releasing factor (CRF), has been given intravenously to six normal men. 100 μg synthetic CRF caused rises in circulating levels of adrenocorticotropic hormone (ACTH) and cortisol but had no effect on levels of prolactin, growth hormone, thyrotropin, or gonadotropins. Its specific action suggests that it, or a related peptide, may be a CRF in man, and it may provide the basis for a new clinical test of pituitary ACTH reserve.

DIRECT INHIBITION OF GASTRIC ACID AND PEPSIN SECRETION BY GROWTH-HORMONE RELEASE-INHIBITING HORMONE IN CATS

Growth-hormone release-inhibiting hormone (G.H.-R.I.H.) inhibited gastric acid and pepsin secretion in response to pentagastrin and food stimulation in cats. This effect is mediated by a direct action on the parietal and peptic cells. No evidence of a post-inhibitory acid or pepsin secretory rebound was obtained. Thus a compound of hypothalamic origin can exert a direct effect on exocrine secretion. In view of its widespread actions and its presence in relatively high concentrations in various organs apart from the hypothalamus, G.H.-R.I.H. might also be regarded as a factor responsible for local coordination of endocrine and exocrine secretion.

GLUCAGON CONTROL OF FASTING GLUCOSE IN MAN

Abstract Infusion of growth-hormone release inhibiting hormone (G.H.-R.I.H.) in four fasting subjects reduced plasma glucagon and insulin concentrations to undetectable levels and this was associated with a highly significant decline in plasma-glucose (28±S.E.M. 3 mg. per 100 ml. in 1 hour, p

GROWTH-HORMONE-RELEASING FACTOR IN GROWTH HORMONE DEFICIENCY: DEMONSTRATION OF A HYPOTHALAMIC DEFECT IN GROWTH HORMONE RELEASE

Four patients with hypothalamic tumours or idiopathic growth hormone (GH) deficiency, who were GH deficient by conventional criteria, responded to 200 micrograms synthetic hpGRF-40 with a clear rise in circulating GH.

Growth hormone releasing factor: comparison of two analogues and demonstration of hypothalamic defect in growth hormone release after radiotherapy.

Human pancreatic growth hormone releasing factor (hpGHRF(1-40] stimulates the release of growth hormone in normal subjects and some patients with growth hormone deficiency. A study comparing the shorter chain amidated analogue hpGHRF(1-29) with an equivalent dose of hpGHRF(1-40) in seven normal subjects showed no significant difference in growth hormone response between the two preparations. Six patients with prolactinomas were also tested; these patients had received megavoltage radiotherapy previously but had developed growth hormone deficiency as shown by insulin induced hypoglycaemia. In all six patients 200 micrograms hpGHRF(1-40) or hpGHRF(1-29)NH2 produced an increase in the serum growth hormone concentration. These data suggest that hpGHRF(1-29)NH2 may be useful for testing the readily releasable pool of growth hormone in the pituitary and that cases of hypothalamo-pituitary irradiation resulting in growth hormone deficiency may be due to failure of synthesis or delivery of endogenous GHRF from the hypothalamus to pituitary cells.

Isolation, structural elucidation and synthesis of a tetradecapeptide with in vitro ACTH-releasing activity corresponding to residues 33–46 of the α-chain of porcine hemoglobin

Abstract A peptide found in acetic acid extracts of porcine hypothalami and capable of stimulating the release of ACTH in vitro was isolated in pure state, structurally identified as Phe-Leu-Gly-Phe-Pro-Thr-Thr-Lys-Thr-Tyr-Pre-Pro-His-Phe and synthesized. This tetradecapeptide, which corresponds to amino acid residues no. 33–46 in the sequence of the α-chain of porcine hemoglobin, probably represents an artefact of extraction or isolation procedures. Since this peptide stimulates ACTH release from rat pituitary fragments and from monolayer cultures of pituitary cells, but not in vivo , caution must be exercised in interpreting the results of in vitro assays for corticotropin releasing factor.

EFFECTS OF PROSOMATOSTATIN ON GROWTH HORMONE AND PROLACTIN RESPONSE TO ARGININE IN MAN Comparison with Somatostatin

The effects of the hypothalamic 28 aminoacid peptide prosomatostatin (Pro-SS) on arginine-induced growth hormone (GH) and prolactin (PRL) release and blood glucose levels in man are compared with those obtained after an equimolar dose of somatostatin (SS). In comparison with SS, Pro-SS caused greater and more prolonged inhibition of GH release, a more marked reduction of the PRL response to arginine, and greater enhancement of the hyperglycaemic action of arginine. The greater potency and prolonged action of Pro-SS make it an interesting tool to study hormonal control mechanisms in a variety of physiological and pathological conditions.

SUPPRESSION OF GONADOTROPHIN RELEASE IN MAN BY AN INHIBITORY ANALOGUE OF L.H.-RELEASING HORMONE

The ability of an inhibitory analogue of L.H.-releasing hormone (L.H.R.H.) to suppress the release of luteinising hormone (L.H.) and follicle-stimulating hormone (F.S.H.) after administration of a small does of L.H.R.H. was tested in four men. A single intramuscular injection of 90 mg (D-Phe-2,D-Trp-3,D-Phe-6)-L.H.R.H. diminished the gonadotrophin response to 25 micrometer of L.H.R.H. given 1, 4, 8, and 24 hours afterwards. Basal levels of L.H. and F.S.H. were not lowered. The results demonstrate that an inhibitory analogue of L.H.R.H. is active in man and suggest the possibility that inhibitors of L.H.R.H. might eventually form the basis of a new method of birth control.