On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

No abstract

A radioimmunoassay was developed to measure corticotrophin-releasing factor (CRF-41) extracted from human plasma using Vycor glass. Assay sensitivity was 20 ng/l and intra- and interassay coefficients of variation were 10.2 and 11.4% respectively. The normal range of plasma CRF-41 was less than 20-110 ng/l (n = 46). Plasma concentrations of CRF-41 in patients with Cushing's disease. Nelson's syndrome and Addison's disease were within the normal range. No correlation was found between CRF-41 and ACTH in these syndromes. Two patients with the ectopic ACTH syndrome had increased plasma concentrations of CRF-41. In normal subjects no changes in plasma CRF-41 occurred after insulin-induced hypoglycaemia, treatment with dexamethasone or feeding, and changes in the concentrations of CRF-41 did not reflect circadian changes in plasma concentrations of cortisol. Concentrations of immunoreactive CRF in plasma of women in the third trimester of pregnancy were increased (550-9300 ng/l) and gel filtration chromatography showed that this comprised CRF-41 and a higher molecular weight form. Reversed-phase high-performance liquid chromatography also revealed multiple peaks of immunoreactive CRF in extracts of plasma and placenta.

The secretion of neurohypophyseal hormone and ACTH in the rat has been shown to exhibit circadian rhythms, with high values during the day and low values throughout the night. The neurohypophyseal hormone daily rhythm is altered by exposure to constant light and by pinealectomy. It was, thus, proposed that the observed fall in vasopressin (AVP), oxytocin, and ACTH over the hours of darkness could be related to the release of melatonin seen at this time. Therefore, a study was performed to determine the effect of melatonin on AVP, oxytocin, and CRH-41 release from the isolated rat hypothalamus in vitro. Employing a previously validated technique, rat hypothalami were incubated in either medium alone or medium containing melatonin or one of two melatonin analogs. Hormone release was measured by RIA, and the ratios were calculated and compared by Student's t test, with Dunnett's correction for multiple comparisons. Melatonin showed a dose-dependent inhibition of both basal and stimulated AVP and oxytocin release in the concentration range 4.3 x 10(-10) to 2.5 x 10(-3) M, while having no significant effect on the release of CRH-41. The two melatonin analogs, 2-iodomelatonin and 5-methoxy-N-isobutanoyltryptamine, were also found to inhibit both basal AVP and oxytocin release, indicating that this effect probably depends upon the presence of melatonin receptors in the hypothalamus. This inhibitory modulation of AVP, in the absence of any effect on CRH-41, suggests that melatonin may affect water balance by means of directly inhibiting hypothalamic AVP release. Furthermore, circadian rhythmicity in pituitary-adrenal activity may depend on melatonin modulation of AVP, rather than changes in CRH-41.

We conclude that not only is leptin stored within the pituitary, but it may also be released from pituitary cells and modulate other pituitary hormone secretion. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function.