ROLE OF ESTROGEN RECEPTOR α AND β IN THE INDUCTION OF PROGESTERONE RECEPTORS IN HYPOTHALAMIC VENTROMEDIAL NEURONS

The estrogen induction of progesterone receptors (PRs) in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvI) is critical for the regulation of female sexual behavior. VMNvI neurons express PRs and both types of estrogen receptors (ER alpha and ER beta), and their sequential activation initiates the molecular mechanisms underlying sexual behavior. To assess the relative importance of each ER subtype in the induction of PRs, we have estimated the total number of PR-immunoreactive neurons and quantified the total amount of PR protein in the VMNvI of adult ovariectomized rats that were injected with either estradiol benzoate (EB) or the specific agonists of the ER alpha, propyl-pyrazole triol (PPT), and of the ER beta, diaryl-propionitrile (DPN), in different doses and schedules. The administration of EB and of PPT alone, but not of DPN alone, increased the total number of PR-immunoreactive neurons and PR protein levels. When the specific agonists were administered sequentially, the total number of PR-immunoreactive neurons also increased, particularly when PPT was administered before DPN. Conversely, the concomitant administration of PPT and DPN did not increase the number of PR-immunoreactive neurons. The observation that PPT increases the number of PR-immunoreactive neurons and the levels of PR protein far less than EB shows that the estradiol induction of PRs in the VMNvI does not involve solely the activation of the ER alpha and suggests that it might also implicate the activation of membrane receptors. The present results also show that ER beta activation averts the action of ER alpha in the induction of PRs. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.