Estrogen dependent activation function of ERβ is essential for the sexual behavior of mouse females

Abstract

We previously generated and characterized a genuine estrogen receptor (ER) β-null mouse line (named ERβ ST L−/L− ) and showed that ERβ ST L−/L− mice were sterile, due to an ovulation impairment in females and to an unknown reason in males, as their reproductive organs and spermatozoid motility appeared normal. We report here an assessment of the sexual behavior of ERβ ST L−/L− null mice. We found that ERβ ST L−/L− males display mildly impaired sexual behavior and that ERβ ST L−/L− females are significantly less receptive and less attractive than wild-type (WT) females. Decreased attractivity is also exhibited by ERβAF2 0 but not by ERβAF1 0 mutant females (females devoid of either AF2 or AF1 activation function of ERβ). Interestingly, by using an odor preference test, we have determined that the low attractiveness of ERβ ST L−/L− and ERβAF2 0 females is related to a deficiency of a volatile chemosignal.T he role of estradiol (E2) and estrogen receptor α (ERα) on the sexual behavior of the mouse is well known (1). ERα-null females do not display sexual receptivity, although they are as sexually attractive as wild-type (WT) controls. ERα-null males exhibit severely reduced numbers of mounts, thrusts and intromissions, and very few ejaculate (2). In contrast, ERβ has not yet been reported to play an important role in mouse sexual behavior (3). Several mouse lines bearing partial null mutations of ERβ have been generated and named according to the laboratory of origin (4, 5): ERβKO CH originated from a Chapel Hill laboratory (6), ERβKO ST from a Strasbourg laboratory (7), and ERβKO WY from Wyeth (8). The ERβKO CH line has been duplicated and a second colony, named ERβKO KI , has been established at the Karolinska Institut (9). A study performed on ERβKO CH males and females showed that they performed normally in sexual behavior tests. Nevertheless, a delay in the age of the first ejaculation was reported in these mice, without further consequences in adults (10), as adults ERβKO CH males were fertile and sired litters with the same efficiency as their WT counterparts (3). Contrasting with an apparent minor role in sexual behavior, ERβ appeared to be a major determinant of antianxiety behaviors in female mice (11,12), and, in a transient manner, of aggressive behaviors in male mice (13). ERβ was also reported to be involved in male mouse brain defeminization (14).We recently reported the generation and characterization of a complete ERβ-null mouse, the ERβ ST L−/L− mouse, of which the morphological phenotype contrasts in many aspects with that of the described ERβKO KI mutant (5). ERβ ST L−/L− females were sterile, due to ovulation impairment, and males exhibited infertility from an unknown reason because their internal and external reproductive organs appeared morphologically normal. Because ERβ ST L−/L− mice of both sexes displayed reproductive anomalies, we performed sex behavioral tests to evaluate the extent of ERβ involvement in mouse reproductive functions. We found that ERβ is required for a normal sexual beh...

Estrogen induces estrogen receptor alpha expression and hepatocyte proliferation in the livers of male mice

“…Most of the actions of estrogens appear to be mediated by three receptors; that is, the estrogen receptors alpha (ERα), beta (ERβ), and G protein‐coupled receptor 30 (GPR30, Antal et al . ; Adlanmerini et al . ; Chimento et al .…”

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

“…The activation of the ERα subtype by its specific agonist propyl‐pyrazole triol (PPT) induces the expression of PRs and increases the number of PR‐immunoreactive neurons in the VMNvl , enhances proceptive behaviors, and increases lordosis quotients . None of these effects has been reproduced by activation of the ERβ subtype , which, in contrast to ERα activation, promotes high rejection quotients both in ER knockout mice and in rats injected with the ERβ‐specific agonist diaryl‐propionitrile (DPN) . There is also evidence that ERβ can modulate ERα activity in a dose‐dependent manner and regulate ERα‐mediated gene transcription .…”

Differential Activation of a Mouse Estrogen Receptor β Isoform (mER β 2) with Endocrine-Disrupting Chemicals (EDCs)

“…ERβ is highly expressed in ovarian granulosa cells where it is required for effective ovulation (Couse et al 2005; Rodriguez et al 2010). Additional studies have suggested ERβ has a role in prostate cancer (Antal et al 2012; Hartman et al 2012). Together, these processes highlight the importance of regulated ERβ signaling.…”