CIRCADIAN PATTERNS OF PLASMA-IMMUNOREACTIVE CORTICOTROPIN, BETA-ENDORPHIN, CORTICOSTERONE AND PROLACTIN AFTER IMMUNONEUTRALIZATION OF CORTICOTROPIN-RELEASING HORMONE

To study the role of corticotropin-releasing hormone (CRH) in the circadian rhythm of circulating corticotropin (ACTH), beta-endorphin (beta-END), corticosterone, and prolactin (PRL), we measured the effects of CRH immunoneutralization over a 24-hour period in chronically cannulated, conscious, freely moving, male Sprague-Dawley rats, maintained at a constant light-dark cycle. Blood samples were collected in the morning (08.00 h), at noon (12.00 h), and in the evening (18.00 h) on the day of treatment, and in the morning (08.00 h) of the next day. Hyperimmune rabbit serum raised against rat CRH (1.0 ml/rat, i.v.) or normal rabbit serum (NRS, 1.0 ml/rat, i.v.) was administered at 08.00 h, immediately after the first blood sample had been collected. CRH immunoneutralization caused no significant decreases in circulating immunoreactive ACTH, beta-END and corticosterone plasma levels at noon, but abolished the evening rises of these hormones. PRL levels were not significantly different between the groups at any time point measured. To compare the effects of CRH immunoneutralization to those of glucocorticoid negative feedback, we measured the effects of dexamethasone (0.5 mg/kg, i.v. at 08.00 h) on the above parameters. ACTH and beta-END concentrations were significantly decreased, and corticosterone and PRL levels were markedly suppressed after glucocorticoid administration both at 12.00 and 18.00 h. However, 24 h after the administration of dexamethasone, PRL concentrations were elevated despite persistently low corticosterone levels. These data suggest that evening elevations of ACTH, beta-END, and corticosterone depend on release of endogenous CRH, while CRH does not appear to play a significant role in maintaining baseline ACTH and beta-END levels in the morning, and resting PRL levels throughout the day.