Age-related decrease in the hypothalamic CRH mRNA expression is reduced by dehydroepiandrosterone (DHEA) treatment in male and female rats.

Abstract

Aging is frequently associated with changes in physiological and cognitive processes. Among these changes, it has been shown that aging has a profound impact on the hypothalamo-pituitary-adrenocortical (HPA) axis. Since there is controversy about the influence of aging on the HPA axis, the first objective of the present study was to clarify the effects of aging on the HPA axis using the genetic expression of hypothalamic corticotropin-releasing hormone (CRH). Changes in the CRH mRNA expression were quantified in the hypothalamic paraventricular nucleus (PVN) using in situ hybridization, in young (50 days) and old (18 months) rats of both sexes. The second objective was to determine the effects of dehydroepiandrosterone (DHEA) treatment on the age-related changes in CRH mRNA in both sexes. In aged animals of both sexes, CRH mRNA levels in PVN were significantly reduced by 20%. DHEA treatment increased the CRH mRNA expression in young rats and reversed the decrease in the CRH mRNA expression in old rats. Young males were more sensitive to DHEA than young females (+15% vs. +9%) whereas in old animals females showed more striking changes than males (+38% vs. +24%). These findings clearly demonstrate that in old apparently healthy rats of both sexes aging process induced a significant decrease in basal CRH mRNA levels and that DHEA treatment which exerts a positive influence on CRH gene expression completely reversed the decrease of the CRH mRNA levels associated with aging.