Sex Differences in Expression of Oestrogen Receptor α but not Androgen Receptor mRNAs in the Foetal Lamb Brain

Abstract

Gonadal steroid hormones play important roles during critical periods of development to organize brain structures that control sexually dimorphic neuroendocrine responses and behaviors. Specific receptors for androgens and estrogens must be expressed at appropriate times during development in order to mediate these processes. The present study was performed to test for sex differences in the relative expression of estrogen receptor-α (ERα) and androgen receptor (AR) mRNA during the window of time in gestation that is critical for behavioral masculinization and differentiation of the ovine sexually dimorphic nucleus (oSDN) in the sheep. In addition, we examined whether ERα and AR mRNA expression is localized within the nascent oSDN and could be involved in its development. Using quantitative RT-PCR, we found that females expressed more ERα mRNA than males in medial preoptic area and medial basal hypothalamus during the mid-gestational critical period for brain sexual differentiation. No sex differences were found for AR mRNA in any tissue examined or for ERα in amygdala and frontal cortex. Using radioactive in situ hybridization, we found that the distributions of ERα and AR mRNA overlapped with aromatase mRNA, which delineates the boundaries of the developing oSDN and identifies this nucleus as a target for both androgens and estrogens These data demonstrate that the transcriptional machinery for synthesizing gonadal steroid receptors is functional in the fetal lamb brain during the critical period for sexual differentiation and suggest possible mechanisms for establishing dimorphisms controlled by gonadal steroids may exist at the level of steroid hormone receptor expression.

Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture

“…These results indicate that testosterone or its estrogenic metabolite could act directly to influence neuronal maturation, rather than or in addition to indirect effects on their afferent inputs, efferent targets or glial interactions. The presence of androgen receptors and aromatase in the cultures agrees with their expression in the same brain regions of sheep during comparable gestational ages in vivo [29–31] and indicates that the culture model has validity for studying steroid hormone action on sheep brain development. The predominant localization of androgen receptor to the cytoplasm may be related to the lack of testosterone in the culture medium during the time course study.…”

A Glance of p53 Functions in Brain Development, Neural Stem Cells, and Brain Cancer

“…Meanwhile, p53 is a target gene of ERα [ 30 ]. It is noteworthy that sexual dimorphism in the expression of sex hormone receptors in mammalian brains have been observed [ 31 , 32 ]. One can speculate that the development of the female brain, which exhibits gender-specific pattern of sex hormone receptor expression, is probably more heavily dependent on p53 and thus more vulnerable to p53 disruption in comparison to that of the male brain.…”

Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord

“…Androgen receptors are also expressed in the developing foetal oSDN . Experiments were performed to test the involvement of ARs in the sexual differentiation of sheep brain .…”