Estrogen receptors α and β have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons.

Progesterone receptor (PR) activation in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female sexual behavior. Estrogen receptor (ER) α, in contrast to ERβ, has been implicated in the induction of PRs. The simultaneous activation of ERα and ERβ, although not increasing the number of PR-immunoreactive neurons in the VMNvl, facilitates lordosis, which suggests that ERβ and/or the ERα-ERβ interaction might play a role in PR dynamics and/or PR expression by individual neurons. To address this question, we used western blot and immunohistochemical studies to determine the amounts and subcellular distributions of both PR isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate or with specific agonists of ERα and ERβ, alone or in association. The present data show that ERα activation does not change PR expression in individual neurons, but increases the number of PRs in the VMNvl, because it increases the number of neurons expressing PRs. Conversely, ERβ activation does not change the total number of PRs in the VMNvl, but increases the labeling intensity of the perikaryal cytoplasm, which suggests that it promotes the transport of PRs from neurites into cell bodies. In addition, the simultaneous activation of ERα and ERβ increases the expression of PRs by individual neurons and, consequently, increases the total number of PRs in the VMNvl. Our findings reveal that individual and simultaneous activation of ERα and ERβ have different effects on the levels and subcellular location of PRs in VMNvl neurons.