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Growth-hormone release-inhibiting hormone (G.H.-R.I.H.) impairs the release of glucagon and insulin as well as G.H. during oral glucose tolerance and intravenous arginine tests; patients with acromegaly, diabetes mellitus, and hypopituitarism as well as healthy individuals were studied. Reciprocal changes in non-esterified fatty acids and plasma-insulin were seen. During the glucose-tolerance tests the rise in plasma-glucose was delayed and the peak values were often higher and more sustained after G.H.-R.I.H. than in control studies, so that glucose tolerance was impaired. Plasma-glucagon levels were suppressed by G.H.-R.I.H. in a patient with a glucagon-secreting tumour.

The primary lesion in Alzheimer's disease and dialysis dementia has been postulated to be an impaired blood-brain-barrier (BBB) permeability that allows neurotoxins like aluminium to reach the central nervous system. The present study shows that aluminium itself affects the permeability of the BBB of rats to small peptides. Intraperitoneal injection of aluminium chloride increased the permeability of the BBB to iodinated N-Tyr-delta-sleep-inducing peptide and beta-endorphin by 60-70%. Thus, aluminium can affect the BBB in ways that might be involved in dementia.

Five of 8 patients with unipolar or bipolar endogenous depressions taking prolyl-leucyl-glycinamide (MIF-I), 75 mg/day, showed substantial improvement within a few days of beginning treatment compared with similar improvement in only 1 of 10 receiving 750 mg/day of MIF-I and only 1 of 5 patients taking placebo. The lower dose of MIF-I was associated with significantly greater improvement than both the higher dose and placebo on all of the rating scales used. The authors suggest that an even lower dose of MIF-I, on the order of 0.1 mg/kg, may have a greater effect as an antidepressant.

Synthetic cyclic growth-hormone release-inhibiting hormone (G.H.-R.I.H) impaired platelet aggregation in each of four healthy men given 6-hour infusions. The effects lasted over 24 hours in three of them. There was no consistent change in platelet-counts during the infusions, but 18 hours after the end of the infusions there was a slight but significant increase in platelet-count. There was no change in prothrombin-time, partial thromboplastin-time, fibrinogen titres, and fibrinogen-degradation products. Incubation of G.H.-R.I.H. with blood in vitro did not affect platelet aggregation. Similar impairment of platelet function has been reported by others in baboons given linear G.H.-R.I.H. Infusions in the four healthy men studied also produced abdominal pain, dizziness, and diarrhœa in three, as have been reported in patients similarly infused. Although other side-effects or impairment of platelet-counts or bleeding-tendencies have not been reported in patients infused for up to 72 hours, caution should be exercised when using G.H.-R.I.H. over extended periods until further data on its toxicity are available.

There is now good evidence that the secretion of LH and FSH from the anterior pituitary gland is controlled principally by the central nervous system and a feedback system, involving sex steroids [1, 2]. The hypothalamus stimulates the secretion of follicle stimulating hormone (FSH), luteinizing hormone (LH) and other pituitary hormones by releasing regulatory substances into portal blood flowing from the median eminence region into the pars distalis [3, 4]. Table 1 lists the known hypothalamic hormones and the new nomenclature we have proposed for them [4]. In this report we shall be concerned only with LH-releasing hormone (LH-RH) and FSH-releasing hormone (FSH-RH). Their function is to augment the secretion of LH and FSH.

A synthetic LH-RH analogue (D-Ala6, Des-Gly-NH210)-LH-RH ethylamide exhibited an increased and prolonged LH-RH/FSH-RH activity in normal women. The integrated amounts of LH and FSH levels for this LH-RH analogue were about nine and five times greater than for the same doses of synthetic LH-RH. It is expected that this synthetic LH-RH analogue might yield more positive results than with LH-RH when used in infertility problems.