Aging abolishes the estradiol-induced suppression and diurnal rhythm of proopiomelanocortin gene expression in the arcuate nucleus.

Abstract

The diurnal rhythms of many physiological functions are disrupted during aging. Underlying these disruptions are age-related alterations in the activity of neurotransmitters and/or their receptors. Estradiol has a significant influence on the pattern of the diurnal rhythms in neurotransmitter function, and responsiveness to estradiol changes with age. We assessed POMC mRNA levels in the arcuate nucleus of young, middle-aged, and old female rats to determine whether aging alters the diurnal rhythm of POMC gene expression in ovariectomized rats and/or changes the responsiveness to estradiol. In addition, we measured serum LH, PRL, and corticosterone levels to evaluate any age-associated interactions between these hormones and POMC mRNA levels. In young animals, estradiol treatment induced a diurnal rhythm and suppressed mean levels of POMC mRNA. In the middle-aged and old rats, the ability of estradiol to suppress POMC mRNA levels and to allow the expression of a diurnal rhythm of POMC mRNA was abolished. Although age-associated changes occurred in serum concentrations of LH, PRL, and corticosterone, they did not correlate with the changes in POMC gene expression. Therefore, our data demonstrate that age-related changes in hypothalamic POMC gene expression do not determine the changes in pituitary hormone secretion. Instead, they suggest that fundamental changes in diurnal function or in the biological clock underlie and differentially regulate the age-related changes in POMC gene expression and LH, PRL, and corticosterone secretion.