Aging impairs estrogenic suppression of hypothalamic proopiomelanocortin messenger ribonucleic acid in the mouse

Altered neuroendocrine sensitivity to estrogen is a characteristic of reproductive aging in female rodents, but its molecular basis is not well understood. The objective of this study was to determine whether altered modulation of hypothalamic proopiomelanocortin (POMC) mRNA by estradiol (E₂) is a component of reduced neuroendocrine sensitivity to estrogen in the aging mouse. Young (4 month-old), middle-aged (13 month-old), and old (25 month-old) C57BL/6J mice were ovariectomized, implanted 2 weeks later with Silastic capsules containing E₂ or cholesterol (CHOL), and sacrificed 3 days later. Hypothalamic POMC mRNA was measured by solution hybridization/RNase protection, using a RNA probe complementary to a fragment of mouse POMC mRNA. In the group with CHOL implants, POMC mRNA was 36% lower in middle-aged and old mice compared to young mice. E₂ treatment reduced POMC mRNA levels by 44% in young mice but failed to lower POMC mRNA in middle-aged and old animals. These results confirm earlier evidence of reduced levels of POMC mRNA in hypothalami of aging rodents and indicate that the ability of E₂ to reduce hypothalamic POMC mRNA is lost by middle age.