Circadian Patterns of Plasma Immunoreactive Corticotropin, Beta-Endorphin, Corticosterone and Prolactin after Immunoneutralization of Corticotropin-Releasing Hormone

Abstract

To study the role of corticotropin-releasing hormone (CRH) in the circadian rhythm of circulating corticotropin (ACTH), β-endorphin (β-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, β-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 β-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, β-END, and corticosterone depend on release of endogenous CRH, while CRH does not appear to play a significant role in maintaining baseline ACTH and β-END levels in the morning, and resting PRL levels throughout the day.

Circadian Variations in the Amplitude of Corticotropin-Releasing Hormone 41 (CRH41) Episodic Release Measured In Vivo in Male Rats: Correlations with Diurnal Fluctuations in Hypothalamic and Median Eminence CRH41 Contents

“…Taken together, these data point to a significant rise in both CRH41 production and release in the evening, at the least as a major central nervous system output driving the circadian ACTH rhythm. They also support earlier indirect arguments showing that immunoneutralization with ovine CRH41 (Ixart et al, 1985) or rat CRH41 (Bagdy et al, 1991;van Oers et al, 1991) blunts the circadian ACTH rhythm. The concentration of the CRH41 messenger RNA precursor in the paraventricular nuclei indicates quite early stimulation of the CRH41-producing machinery, starting in the morning and culminating in the evening (Kwak et al, 1992), at about the time when the hypothalamic accumulation of the processed neurohormone and its release at the neurohemal junction were measured in the present study.…”

Chronic Iodine Deprivation Attenuates Stress‐Induced and Diurnal Variation in Corticosterone Secretion in Female Wistar Rats

“…Bagdy et al . (24) have also demonstrated that CRH immunoneutralization abolished the evening rise in corticosterone in male Sprague‐Dawley rats. While a deficit in CRH may explain the loss of a diurnal rhythm in the PTU‐treated rats, there appears to be no such deficit in iodine‐deficient animals to explain the loss of rhythmicity, although more subtle changes to CRH synthesis and release may have occurred.…”

“…(24) have also demonstrated that CRH immunoneutralization abolished the evening rise in corticosterone in male Sprague-Dawley rats. The effect of noise stress (114 dBr10 min commencing at 08.00 h; hatched bar) on plasma corticosterone concentrations in female Wistar rats fed (A) a low iodine diet for six months (LOW IODINE) or a low iodine diet followed by restoration of a normal diet for one month (RESTORED), and (B) propylthiouracil (PTU) or PTU+T 3 for 6 months compared with control animals receiving a normal diet throughout (NORMAL).…”

A Diurnal Rhythm of Stimulatory Input to the Hypothalamo–Pituitary–Adrenal System as Revealed by Timed Intrahypothalamic Administration of the Vasopressin V1Antagonist

“…Contrary to the corticosterone data, ACTH levels showed no diurnal variation during the different Ringer's infusions ( p Ͼ 0.5), although variability during the CT10 experiment was considerably higher than at any other time of the day (16.8 Ϯ 2.8 vs 6.8 Ϯ 1.9, 7.6 Ϯ 2.3, 10.6 Ϯ 1.1, and 11.0 Ϯ 2.4 pg/ml). A number of previous studies have reported diurnal variations in plasma ACTH levels Carnes et al, 1989;Bagdy et al, 1991;Kwak et al, 1992;Ixart et al, 1993), but quite a few others failed to detect significant diurnal variations (Wilkinson et al, 1979;Akana et al, 1986;Carnes et al, 1986;Cascio et al, 1987;Kwak et al, 1993;Suemaru et al, 1995). Important factors that may contribute to the difficulty of finding a circadian ACTH rhythm are the low amplitude of the rhythm, the episodic secretion of ACTH, the sampling protocol used (Carnes et al, 1986;Turek and Van Cauter, 1988;Carnes et al, 1989), and the assay variability (e.g., CT times in different assays).…”