Concentrations of POMC-derived neuropeptides are reduced in hypothalami of aged rodents, whereas levels of POMC products in the pituitary are usually either unchanged or increased. Whether these changes reflect altered synthesis or processing of POMC or altered expression of the POMC gene has not been established. We, therefore, measured POMC mRNA in hypothalami and pituitaries of young (7-month-old), middle-aged (15-month-old), and old (31-month-old) female mice, using slot blot hybridization of total RNA to riboprobes synthesized from cloned POMC DNA fragments. Concentrations of poly(A) and ribosomal RNA were also determined, using probes synthesized from poly(T) and a cloned ribosomal DNA fragment, respectively. Hypothalamic POMC mRNA content and concentration were 30% lower in old than in young and middle-aged mice (P ≪ 0.01). This change was not due to a general decline in hypothalamic mRNA or rRNA levels, neither of which changed with age. In contrast to the hypothalamus, the relative concentration of POMC mRNA in the pituitary nearly doubled in old mice (P ≪ 0.01). This increase was secondary to a decrease in other RNA species, however, since the total pituitary content of POMC mRNA did not differ between young and old mice. These results indicate that the regulation of POMC gene expression during aging differs in hypothalamus and pituitary, and that reduced levels of hypothalamic POMC mRNA may account for the previously reported reductions in concentrations of hypothalamic POMC peptides during aging.
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