Site-specific effects of intracranial estradiol administration on recurrent insulin-induced hypoglycemia in the ovariectomized female rat
Abstract
Clinical and experimental studies reveal gender differences in susceptibility to dampening effects of precedent hypoglycemia on recurrent insulin-induced hypoglycemia (RIIH). Recent studies implicate the ovarian steroid, estradiol, in the regulation of RIIH, since systemic replacement of this hormone at basal estrous cycle levels maintains glucose profiles during serial insulin dosing and prevents RIIH-associated reductions in neuronal activation in key metabolic structures in the ovariectomized female rat brain. The present study investigated the hypothesis that these effects are achieved, in part, by estrogenic action within the central nervous system, including glucoregulatory structures characterized by high estrogen receptor (ER) expression. Initial experiments evaluated the impact of global intracranial administration of estradiol on RIIH. Ovariectomized rats were treated by continuous infusion of graded doses of 17β-estradiol-3-benzoate (EB) or vehicle into the lateral ventricle (LV), and injected subcutaneously with 1 or 4 doses of the intermediate-release insulin, Humulin N (HN), 1 dose per day. Animals infused with 5 or 10 µg EB/day exhibited uniform glycemic responses to 1 versus 4 doses of insulin, whereas rescue fr...Continue Reading
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Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system
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