Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Abstract

This study reports on the spatiotemporal dynamics of the expression of estrogen receptors (ERs) in the mouse central nervous system (CNS) during the early postnatal and the peripubertal period. At postnatal day 7 (P7), neurons with strong nuclear immunostaining for both ERa and ERb1 were widely distributed throughout the brain. Sucrose density gradient sedimentation followed by western blotting supported the histochemical evidence for high levels of both ERs at P7. Over the following 2 days, there was a rapid downregulation of ERs. At P9, ERa expression was visible only in the hypothalamic area. Decline in ERb1 expression was slower than that of ERa, and ERa-negative, ERb1-positive cells were observed in the dentate gyrus and walls of third ventricle. Between P14 and P35, ERs were undetectable except for the hypothalamic area. As before P7, the ovary does not produce estrogen but does produce 5a-androstane-3b, 17b-diol (3bAdiol), an estrogenic metabolite of dihydrotestosterone, we examined the effects of high levels of 3bAdiol in the postnatal period. We used CYP7B1 knockout mice which cannot hydroxylate and inactivate 3bAdiol. The brains of these mice are abnormally large with reduced apoptosis. In the early postnatal period, there was 1-week delay in the timing of the reduction in ER expression in the brain. These data reveal that the time when ERs might be activated in the brain is limited to the first 8 postnatal days. In addition, the importance of aromatase has to be reconsidered as the alternative estrogen, 3bAdiol, is important in neuronal function in the postnatal brain.

Targeting estrogen receptor β in microglia and T cells to treat experimental autoimmune encephalomyelitis

“…The ERβ antibody was homemade, raised in hens immunized with ERβ protein and purified from egg yolks. It has been used extensively in mouse brain and spinal cords (44)(45)(46)(47), as well as in mouse and human prostates and mammary glands (48,49). For cell counting, we took every fifth slice from 25 consecutive slices, that is, five slices from each mouse.…”

Regulation of estrogen receptor beta activity and implications in health and disease

“…High ERb levels are maintained throughout birth and the first two postnatal weeks, whereas they drop significantly between postnatal day 14 and 35. Four months after birth, however, they increase again [138].…”

“…The abundance of ERb in different tissues varies during development, via unknown regulatory mechanisms, suggesting an important role of ERb-mediated estrogen action in the maturation of fetal and postnatal tissues [136][137][138].…”

Tissue-Specific Regulation of Sex Hormone Biosynthesis and Metabolism: Novel Aspects on Hormonal Signalling and Maintenance of Cellular Steroid Levels

“…Also, the enzymes known to form important hormones in this tissue such as CYP17A1, 5-reductase and the 3-and 17-hydroxysteroid dehydrogenases have attracted interest as potential or existing targets for therapy aimed at controlling cellular hormone levels (Hudak et al, 2006;Norlin;Sharifi, 2010;Vihko et al, 2006). Considering its role in metabolism of ER ligands, CYP7B1 has been linked to estrogenic action by several studies and investigators (Petterson et al, 2010;Sugiyama et al, 2009;Weihua et al, 2002). However, the actions of CYP7B1 in sex hormone metabolism do not seem to be limited to estrogenic signalling.…”

“…In addition, the presence or absence of other hormone ligands with higher affinitity for the receptor as well as the effects of tissue-specific comodulators should play important roles. These different possibilities open for enzymatic control of cell-specific actions, depending on e. g. comodulator expression, substrate availability, and substrate competition Shapiro et al, 2011;Sugiyama et al, 2009). The most potent androgenic hormone in the human body is dihydrotestosterone (DHT).…”