Regulation of ERα protein expression by 17β-estradiol in cultured neurons of hypothalamic ventromedial nucleus

The activation of the subtype α of estrogen receptors (ERα) in the hypothalamic ventromedial nucleus (VMNvl) is required to stimulate female sexual receptivity. Moreover, the hormone was found to govern the expression of the receptor. Its removal due to ovariectomy and subsequent substitution suggest that the hormone down-regulates the expression of ERα. In contrast, in normally cycling animals the expression of the receptor peaks at proestrus, the phase of highest concentration of 17β-estradiol in estrous cycle. Therefore, in this study we examined the influence of the hormone on ERα expression in primary dissociated cultures of neurons isolated from the VMNvl of young adult female rats. Measurements of ERα immunofluorescence revealed that both supraphysiological and physiological concentrations of 17β-estradiol increase the expression of ERα. Analyses with selective agonists showed that both nuclear ERs are able to mediate the action of the hormone. However, the activation of ERα had a stronger effect on the expression of its own receptor than the activation of ERβ. Simultaneous activation of both receptors attenuated the influence of ERα alone. Physiological concentrations of progesterone were found to revoke the effect of 17β-estradiol, whereas the expression of ERα is up-regulated by progesterone alone. These data indicate that the expression of ERα in VMNvl neurons is under the control of both types of nuclear ERs and, in addition, progesterone receptors (PRs). The particular contribution of the receptors is dependent on their level of expression and the hormonal context. In neurons expressing high quantity of ERα, ERβ attenuates the overall expression of the receptor, whereas in cells containing mostly ERβ it contributes to the up-regulation of ERα synthesis. Simultaneous activation of ERs and PRs reverses the influences of the receptors due to inter-inhibition of their transcriptional activities.