Age-Related Changes in Proopiomelanocortin (POMC) Gene Expression in the Periarcuate Region of Ovariectomized Rats

Abstract

Aging of the female reproductive system results in a decline in estrous cyclicity which is due, in part, to alterations in hypothalamic function. Opioid peptides, especially the proopiomelanocortin (POMC)-derived neuropeptide, beta-endorphin, are thought to play a role in maintaining normal patterns of LH secretion. Previous studies have shown that the level of hypothalamic beta-endorphin and POMC messenger RNA (mRNA) decreases in old animals; however, it is unknown whether opioid peptides are involved in age-related reproductive decline. To determine whether POMC gene expression changes with age and is related to reproductive status, we assessed POMC mRNA levels by in situ hybridization histochemistry in the periarcuate region of young (3-4 months), middle-aged (10-12 months), and old (17-19 months) ovariectomized rats. Two methods of quantitation were used: 1) slides were apposed to x-ray film and POMC mRNA levels were quantitated over the entire periarcuate region, and 2) the same slides were dipped in emulsion and the level of POMC was quantitated in individual cells. POMC mRNA levels decreased 20-30% by the time animals were middle-aged, and no further decline was noted in the old animal groups. The decrease in POMC mRNA levels in the middle-aged and old animals occurred regardless of their reproductive status prior to ovariectomy. In addition, there was a 30-40% decline in the number of cells expressing POMC mRNA in middle-aged and old animals, suggesting an overall age-related decline in POMC gene expression in middle-aged and old animals independent of reproductive status.