Effects of organisational oestradiol on adult immunoreactive oestrogen receptors (α and β) in the male mouse brain

Steroid hormones act on developing neural circuits that regulate the hypothalamic-pituitary-gonadal axis and are involved in hormone-sensitive behaviours. To test the hypothesis that developmental exposure to oestradiol (E2) organises the quantity of adult oestrogen receptors (ERα and ERβ), we used male mice with a targeted mutation of the aromatase enzyme gene (ArKO) and their wild-type (WT) littermates. These mice are unable to aromatise testosterone to E2, but still express both ERα and β. To evaluate adult responsiveness to E2, gonadectomised males were implanted with Silastic capsules containing E2, or an empty implant, 5 days prior to sacrifice. Immunoreactivity for ERα and ERβ was quantified in the caudal ventromedial nucleus (VMN) and the medial preoptic area (POA). Regardless of genotype, adult treatment with E2 reduced ERα-immunoreactive (ir) and ERβ-ir cell numbers in the POA, as well as ERβ-ir, but not ERα-ir, cell numbers in the VMN. Genotype, and thus endogenous exposure to E2, produced opposite effects on ER expression in the two brain areas. In the VMN, ArKO males had more ERα-ir and ERβ-ir cells than did WT males. In the POA, ArKO males had fewer ERα-ir and ERβ-ir cells than did WT males. Thus, numbers of immunoreactive neurones containing both ERs in the adult ArKO male were enhanced in the POA, but decreased in the VMN, and most likely these patterns were established during the developmental critical period. Furthermore, although both ERα and β-ir cell numbers are altered by the disruption of the aromatase gene, ERβ is altered in a more robust and region-specific manner.