AGE-RELATED DECREASE IN THE HYPOTHALAMIC CRH MESSENGER-RNA EXPRESSIONIS REDUCED BY DEHYDROEPIANDROSTERONE (DHEA) TREATMENT IN MALE AND FEMALE RATS

Aging is frequently associated with changes in physiological and cogni tive processes. Among these changes, it has been shown that aging has a profound impact on the hypothalamo-pituitary-adrenocortical (HPA) ax is. Since there is controversy about the influence of aging on the HPA axis, the first objective of the present study was to clarify the eff ects of aging on the HPA axis using the genetic expression of hypothal amic corticotropin-releasing hormone (CRH). Changes in the CRH mRNA ex pression were quantified in the hypothalamic paraventricular nucleus ( PVN) using in situ hybridization, in young (50 days) and old (18 month s) rats of both sexes. The second objective was to determine the effec ts of dehydroepiandrosterone (DHEA) treatment on the age-related chang es in CRH mRNA in both sexes. In aged animals of both sexes, CRH mRNA levels in PVN were significantly reduced by 20%. DHEA treatment increa sed 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 femal es showed more striking changes than males (+38% vs. +24%). These find ings clearly demonstrate that in old apparently healthy rats of both s exes aging process induced a significant decrease in basal CRH mRNA le vels and that DHEA treatment which exerts a positive influence on CRH gene expression completely reversed the decrease of the CRH mRNA level s associated with aging.