ESTRADIOL ABOLISHES AUTOLOGOUS DOWN-REGULATION OF GLUCOCORTICOID RECEPTORS IN BRAIN

We have previously reported that estrogen treatment of steroid-free, ovariectomized-adrenalectomized (OVX-ADX) rats, increased binding to glucocorticoid type II receptors (GR) in some brain regions. The present report studied the effects of estradiol in OVX-ADX rats receiving chronic corticosterone (CORT) treatment. Using binding assays, GR was reduced by CORT replacement in cytosol of hippocampus and septum, but not in whole hypothalamus. GR were recovered after 4 days of estradiol therapy. Using Mab7, a monoclonal antibody against the activated nuclear form of GR, we observed that estrogen treatment increased immunoreactivity measured by computerized densitometry in areas targeted by glucocorticoids. Significantly higher staining for GR developed in CA1 and CA2 hippocampal subfields, paraventricular nucleus of the hypothalamus and lateral ventral septal nuclei of estradiol-receiving, CORT-treated OVX-ADX rats. The amplification of the glucocorticoid biological signal by female sex hormones, may thus affect several neuroendocrine parameters and the outcome of stress-related diseases.