Effects of gonadal steroids and of estrogen receptor agonists on the expression of estrogen receptor alpha in the medial preoptic nucleus of female rats

• Progesterone induces replenishment of ERα in the MPN.
• Agonistic activation of each ER decreases the total number of ERα-ir MPN neurons.
• The repressive action of ERβ disappears when both ERs are simultaneously activated.
• ERβ-dependent reduction in ERα expression is seen in all MPN divisions.
• ERα-dependent reduction in ERα expression is seen in the medial MPN.

The medial preoptic nucleus (MPN) is a sexually dimorphic cell group of the medial preoptic area that plays a central role in the integration of olfactory and hormonal stimuli that modulate sexually differentiated behaviors. The influence of sex steroids in these behaviors is mediated through activation of estrogen receptors (ERs), which are highly expressed in this nucleus. Little is known about the effects of progesterone (P) or the selective activation of each ER subtype on the expression of estrogen receptor alpha (ERα) in the MPN of female rats. We have addressed this subject in the current investigation by estimating, using stereological tools, the total number of MPN neurons that express ERα in rats at each phase of the estrous cycle and in ovariectomized rats treated with estradiol benzoate (EB), P or the ERα- and estrogen receptor beta (ERβ)-specific agonists. Results show that the total number of ERα-immunoreactive neurons does not change over the estrous cycle, except at proestrus when the number is reduced. A similar effect was observed after the administration of EB, but not of P. Results also show that the estradiol-induced down-regulation of the ERα is mediated by activation of both ER subtypes, and that ERβ activation leads to a reduction in the total number of ERα-immunoreactive neurons that is twice that resulting from ERα activation. Present data suggest that ERα activation triggers a sort of negative feedback mechanism in MPN neurons that reduces its own expression, which might be of importance for the regulation of estradiol-dependent physiological and behavioral responses.

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