Estrogen stimulates gonadotropin-releasing hormone release from rat hypothalamus independently through catecholamine and histamine in vitro

Estradiol is known to stimulate gonadotropin-releasing hormone release from the rat medio-basal hypothalamus. Studies were made in an in vitro perifusion system on whether catecholamine and/or histamine was involved in estradiol-induced GnRH release. Normal cycling female rats were decapitated in diestrus II and their medio-basal hypothalami were combined and, perifused with Earl's balanced salt solution containing 0.01% bovine serum albumin bubbled with 95% O2 and 5% CO2. The levels of norepinephrine, dopamine, and histamine and of GnRH in the effluent were measured by HPLC and radioimmunoassay, respectively. Administration of 10(-6) mol/l estradiol resulted in releases of norepinephrine, dopamine, histamine and GnRH at levels of 98, 70, 91 and 288%, respectively, of initial values. Administration of 10(-6) mol/l norepinephrine or dopamine resulted in no increase in histamine release, and administration of 10(-6) mol/l histamine did not increase release of norepinephrine or dopamine. These data suggest that estradiol stimulates the releases of GnRH, catecholamine and histamine from the rat medio-basal hypothalamus, and that it increases GnRH release independently through catecholamine and histamine. As we found previously that norepinephrine or histamine stimulates GnRH release from the medio-basal hypothalamus, we conclude that estradiol stimulates releases of norepinephrine and histamine, resulting in GnRH release from the medio-basal hypothalamus.