Estrogen induction of glial heat shock proteins: implications for hypothalamic aging

In the aging mammalian hypothalamus, a unique subpopulation of glial cells accumulates peroxidase-positive cytoplasmic inclusions distinct from lipofuscin. In adult rodents, this senescence-dependent glial granulation is accelerated by administration of estradiol valerate. In the present study, brain sections derived from male rats given 3 monthly intramuscular injections of estradiol valerate (0.2 mg or 2.0 mg) were immunostained for heat shock proteins and glial fibrillary acidic protein to determine whether a glial stress response is implicated in estrogen-induced granulation. Our findings indicate that estrogen elicits a heat shock response and subsequent granulation in astrocytes residing in estradiol receptor-rich brain regions including the arcuate nucleus and the wall surrounding the third ventricle but not in estradiol receptor-deficient regions such as the striatum and corpus callosum. The heat shock proteins induced by estrogen, namely, the 27, 72, and 90 kDa stress proteins, are upregulated in astrocytes in response to oxidative challenge supporting our hypothesis that estrogen mediates senescent changes in the rodent hypothalamus through oxidative mechanisms.