Regulation of oestrogen receptor mRNA in rat central nervous system

The gonadal steroid l7 -ß oestradiol (E2) influences a variety of neural activities, not only those involved in aspects of reproductive physiology but also in other functions, including autonomic regulation and cognitive processes. The effects of sex steroid hormones are principally, although not exclusively, mediated by binding to their cognate intracellular receptors to regulate functions of their target cells. The expression of these receptors is an important determinant of the actions of steroid hormones. There are two principal oestrogen receptors (ER) characterised to date, ER -a and ER -ß, the products of two distinct genes.Using quantitative in situ hybridisation histochemistry we first described the distribution of neurones expressing the messenger ribonucleic acid (mRNA) moieties for both types of ER in rat brain. We then investigated whether changes in the expression of these transcripts occur in response to hormonal manipulations as well as physiological stimulation in two discrete regions: the hippocampus, involved in memory, behaviour and regulation of the hypothalamo- pituitary- adrenal (HPA) axis and the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, producing oxytocin and vasopressin, and autonomic regulation. Both ER -a and -ß mRNAs were found to be expressed in the hippocampus, while only ER -ß mRNA was localised in the PVN and SON.In the hippocampus, changes in the expression of both mRNA transcripts following gonadectomy were found in a region- and time -specific manner and displayed a sexual dimorphic pattern. However, replacement of E2 in ovariectomised rats did not restore the basal level of expression indicating that factors other than the ligand itself are involved in mediating effects of gonadectomy. Hippocampal neurones also express GR and MR, receptors by which adrenal steroid hormones act through. Because glucocorticoids might act by heterologous regulation of ER mRNA expression, the effects of decreasing or increasing corticosteroid secretion were studied.None of the adrenal manipulations changed ER -a expression, but adrenalectomy decreased ER -p mRNA expression, only in CA1, and this was prevented by corticosterone replacement. Repeated stress for 72 h had no effect on either ER -a or -ß mRNA expression in the hippocampus.The expression of ER -ß mRNA was found in regions containing oxytocin and vasopressin magnocellular neurones; expression in the PVN was low in the medial parvocellular neurones, projecting to the median eminence, but high in the ventral group of parvocellular neurones which project to brainstem and spinal cord.In the SON the greater ER-I3 mRNA signal found in female than in male rats was abolished by gonadectomy, but not restored or altered in intact male rats by E2 treatment. In the ventral parvocellular neurones, we found no sex difference in the expression of ER-E3 mRNA. Here, ovariectomy significantly increased the expression of ER -ß mRNA. The expression of ER-E3 mRNA in both the magno- and parvocellular neurones was not changed at the end of pregnancy, when oestrogen secretion is maximal. In contrast, marked changes in ER -ß mRNA expression were found in SON and PVN neurones, but not in the hippocampus, following manipulation of adrenal- corticoid secretion. First, bilateral adrenalectomy, removing gluco- and mineralo- corticoids, significantly increased ER -ß mRNA expression in the SON but not in the ventral parvocellular neurones. The effect of adrenalectomy was partially reversed by replacement with corticosterone. Stimulation of the HPA axis by repeated stress did not alter expression of ER -ß mRNA, except in the ventral parvocellular neurones where expression was significantly increased. Stimulating the magnocellular neurones by salt -loading markedly attenuated the expression of ER -p mRNA selectively in these neurones, and also in the ventral parvocellular PVN neurones.The results indicate actions of E₂ via ER -α/-ß in hippocampus, but only via ER-ß in the PVN /SON; there is a weak, regionally-specific regulation of ER-α/-ß by sex steroids. In contrast, ER-ß in magnocellular neurones may be up- regulated by gluco- and mineralo- corticoid deficiency, and down- regulated by physiological stimulation of the neurones. This would alter any ER- mediated effects of E₂ on the neurones in these state