Changes in sleep-endocrine activity after growth hormone-releasing hormone depend on time of administration

When administered intravenously (i.v.) in a pulsatile mode during the first half of the night to young normal controls, growth hormone-releasing hormone (GHRH) results in increased growth hormone (GH) plasma levels and slow wave sleep (SWS) and blunted cortisol release. In the present study we investigated whether GHRH has the same effects when administered in the early morning. Seven normal young male volunteers had 2 sessions each in the sleep laboratory (23.00 to 10.00 h) during which the secretion of GH, cortisol and corticotropin (ACTH) and polygraphic recording were monitored. Verum (4 bolus injections of 50 micrograms GHRH) or placebo were injected i.v. at 04.00, 05.00, 06.00 and 07.00 h. GHRH stimulated GH plasma levels significantly whereas cortisol and ACTH were not altered. In the sleep-electroencephalogram, only rapid-eye-movement density was decreased significantly during the period of active medication; all other sleep parameters were unaffected. We suggest that the physiological occurring high activity of the hypothalamic-pituitary-adrenocortical(HPA) system in the early morning prevents the effects of GHRH on cortisol plasma levels and SWS. Thus GHRH administered to healthy young men in the early morning hours has the same effect as GHRH administered during the first half of the night to patients with major depression who have HPA hyperactivity throughout the day.