ESTROGEN INDUCTION OF GLIAL HEAT-SHOCK PROTEINS - IMPLICATIONS FOR HYPOTHALAMIC AGING

In the aging mammalian hypothalamus, a unique subpopulation of glial c ells accumulates peroxidase-positive cytoplasmic inclusions distinct f rom lipofuscin. In adult rodents, this senescence-dependent glial gran ulation 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 immuno-stained for heat shock proteins and glial fibrillary acidic pr otein to determine whether a glial stress response is implicated in es trogen-induced granulation. Our findings indicate that estrogen elicit s a heat shock response and subsequent granulation in astrocytes resid ing in estradiol receptor-rich brain regions including the arcuate nuc leus 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 9 0 kDa stress proteins, are upregulated in astrocytes in response to ox idative challenge supporting our hypothesis that estrogen mediates sen escent changes in the rodent hypothalamus through oxidative mechanisms .