Age-related changes in the diurnal rhythm of CRH gene expression in the paraventricular nuclei.

A circadian rhythm secretion of corticotropin-releasing hormone (CRH) is thought to regulate the circadian pattern of secretion of adrenocorticotropic hormone and corticosterone. We have previously reported that the amplitude of the diurnal rhythm of serum corticosterone concentrations decreases in 17- to 20-mo-old rats. In the present experiment, we tested whether an age-related alteration in the daily rhythm and/or level of CRH mRNA in the paraventricular nuclei (PVN) occurs during middle age. Groups of young and middle-aged animals were killed at several times of day. We assessed the level of CRH mRNA in the PVN and dorsal medial subdivision of the PVN using in situ hybridization. In young rats, CRH mRNA expression exhibited a diurnal rhythm in the dorsal medial PVN. The same trend was observed in the entire medial PVN. In middle-aged rats, no rhythm was detected in either region. The overall average level of CRH mRNA was not different between these two age groups. These findings suggest that changes in the suprachiasmatic nucleus or in its ability to entrain neuroendocrine outputs occur relatively early during the aging process.