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

The possible correlation between the circadian and episodic release of corticotropin-releasing hormone 41 (CRH41) in male rats was explored in a comparative study, including the measurement at 0700 hr and 1700 hr of (1) the quantitative parameters of the episodic release pattern of CRH41 into the push-pull-cannulated median eminence (ME); (2) CRH41 content measured by radioimmunoassay in the hypothalamus, and immunocytochemically in the ME; and (3) plasma adrenocorticotropic hormone (ACTH). The data showed that in early evening, the 3.4-fold rise in plasma ACTH coincided with a doubling of CRH41 content in the hypothalamus and in the ME, and of the CRH41 release from the perfused ME. The immunocytochemical data further indicated that the ME area labeled with CRH41 immunoreactivity, rather than the labeling intensity of CRH41-stained neurons, increased in the evening, which may point to an evening recruitment of additional CRH41-producing neurons as the origin of the evening increment in CRH41 and ACTH releases. Finally, the computerized analysis of the CRH41-releasing pattern with three different algorithms (Pulsar, Ultra, and the Santen and Bardin algorithm) showed for the first time that the evening rise in CRH41 output was associated with correlative increases of three parameters of the episodic pattern—peak amplitude (+ 55% to + 80%), peak duration (+ 20%), and mean absolute peak values (+ 73%)-while the pulse frequency remained at the baseline level of 3 cycles · hr-1. The data suggest the occurrence of a connection between the circadian pacemaker and the machinery generating the episodic release of CRH41.