Hypothalamic Expression of Oestrogen Receptor α and Androgen Receptor is Sex‐, Age‐ and Region‐Dependent in Mice

Abstract

Sex steroid hormones act on developing neural circuits regulating the hypothalamic-pituitary-gonadal axis and are involved in hormone-sensitive behaviours. These hormones act mainly via nuclear receptors, such as oestrogen receptor (ER)-α and androgen receptor (AR). By using immunohistochemistry, we analysed the expression level of ERα and AR throughout perinatal life [at embryonic (E) day 19 and postnatal (P) days 5, 15 and 25] and in adulthood in several hypothalamic nuclei controlling reproduction in both wild-type and aromatase knockout (ArKO) (i.e. which cannot convert testosterone into oestradiol) mice to determine whether there are sex differences in hypothalamic ERα and AR expression and, if so, whether these are established by the action of oestradiol. As early as E19, ERα immunoreactivity (-IR) was observed at same expression levels in both sexes in the anteroventral periventricular nucleus (AVPv), the medial preoptic area (MPOA), the bed nucleus of the stria terminalis (BnST), the ventrolateral part of the ventromedial hypothalamic nucleus and the arcuate nucleus (ARC). Sex differences (female > male) in ERα-IR were observed not only during the prepubertal period in the BnST (P5 to P25) and the MPOA (P15), but also in adulthood in these two brain regions. Sex differences in AR-IR (male > female) were observed at P5 in the AVPv and ARC, and at P25 in the MPOA and ARC, as well as in adulthood in all hypothalamic regions analysed. In adulthood, gonadectomy and hormonal treatment (oestradiol or dihydrotestosterone) also strongly modulated ERα-IR and AR, respectively. Taken together, sex differences in ERα-IR and AR-IR were observed in all hypothalamic regions analysed, although they most likely do not reflect the action of oestradiol because ArKO mice of both sexes showed expression levels very similar to wild-type mice throughout perinatal development.

Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice

“…The total amount of immunoreactivity (ir) for each receptor was analyzed as previously described (Brock et al, 2010;2015) Briefly, one representative section was selected for several brain nuclei and was digitized using a video camera (CFW 1612C; Scion Corp., Frederick, MD, USA) attached to a microscope (MTV-3, x 20 objective; Olympus, Tokyo, Japan). Then, immunoreactivity was quantified with a computer-based image analysis system using the particle-counting protocol of NIH IMAGE, version 1.49® (Wayne Rasband, NIH,…”

Impact of Proestrus on Gene Expression in the Medial Preoptic Area of Mice

“…The classical, estrogen receptor 1(ER-alpha; Simerly et al, 1990; Merchenthaler et al, 2004), the novel subtype, estrogen receptor 2 (ER-beta; Shughrue et al, 1997; Merchenthaler et al, 2004; Zuloaga et al, 2014) and the membrane-associated form GPER1 (Treen et al, 2016) have all been identified and mapped in different structural compartments of the region. Signaling to the region by progesterone and androgen hormones has also been demonstrated and the cellular distribution of their receptors elucidated (Handa et al, 1986; Simerly et al, 1990; Kanaya et al, 2014; Brock et al, 2015). The KP/GABA/glutamate neurons of the region are exceptional targets of gonadal hormones, including E2.…”

Sex differences in the brain–an interplay of sex steroid hormones and sex chromosomes

“…In contrast with the SDN MPOA, AVPV is larger in females than in males [79,80]. In AVPV, the sex difference was described in the number of cells expressing alpha and β oestrogen receptors, with females having more immunopositive cells for both receptors [81][82][83][84], and tyrosine hydroxylase, a marker for dopaminergic cells, which are also present in higher numbers in female AVPV [85,86]. Sex differences were also observed in the expression of kisspeptin, a regulator of GnRH secretion essential for the onset of puberty.…”