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Sex differences in expression of oestrogen receptor ? but not androgen receptor mRNAs in the foetal lamb brain.

ABSTRACT: Gonadal steroid hormones play important roles during critical periods of development to organise brain structures that control sexually dimorphic neuroendocrine responses and behaviours. Specific receptors for androgens and oestrogens must be expressed at appropriate times during development to mediate these processes. The present study was performed to test for sex differences in the relative expression of oestrogen receptor (ER)? and androgen receptor (AR) mRNA during the window of time in gestation that is critical for behavioural masculinisation and differentiation of the ovine sexually dimorphic nucleus (oSDN) in the sheep. In addition, we examined whether ER? and AR mRNA expression is localised within the nascent oSDN and could be involved in its development. Using the quantitative real-time polymerase chain reaction, we found that females expressed more ER? 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 ER? in amygdala and frontal cortex. Using radioactive in situ hybridisation, we found that the distributions of ER? 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 oestrogens. These data demonstrate that the transcriptional machinery for synthesising gonadal steroid receptors is functional in the foetal lamb brain during the critical period for sexual differentiation and suggest that possible mechanisms for establishing dimorphisms controlled by gonadal steroids may exist at the level of steroid hormone receptor expression.

SUBMITTER: Reddy RC

PROVIDER: S-EPMC4071168 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Sex differences in expression of oestrogen receptor α but not androgen receptor mRNAs in the foetal lamb brain.

Reddy R C RC Estill C T CT Meaker M M Stormshak F F Roselli C E CE

Journal of neuroendocrinology 20140501 5

Gonadal steroid hormones play important roles during critical periods of development to organise brain structures that control sexually dimorphic neuroendocrine responses and behaviours. Specific receptors for androgens and oestrogens must be expressed at appropriate times during development to mediate these processes. The present study was performed to test for sex differences in the relative expression of oestrogen receptor (ER)α and androgen receptor (AR) mRNA during the window of time in ges ...[more]

PMID: 24730418

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Project description:IntroductionSex differences in brain cortical function affect cognition, behaviour and susceptibility to neural diseases, but the molecular basis of sexual dimorphism in cortical function is still largely unknown. Oestrogen and oestrogen receptors (ERs), specifically ERβ, the most abundant ER in the cortex, may play a role in determining sex differences in gene expression, which could underlie functional sex differences. However, further investigation is needed to address brain region specificity of the effects of sex and ERβ on gene expression. The goal of this study was to investigate sex differences in gene expression in the mouse posterior cortex, where sex differences in transcription have never been examined, and to determine how genetic ablation of ERβ affects transcription.MethodsIn this study, we performed unbiased transcriptomics on RNA from the posterior cortex of adult wild-type and ERβ knockout mice (n = 4/sex/genotype). We used unbiased clustering to analyse whole-transcriptome changes between the groups. We also performed differential expression analysis on the data using DESeq2 to identify specific changes in gene expression.ResultsWe found only 27 significantly differentially expressed genes (DEGs) in wild-type (WT) males vs females, of which 17 were autosomal genes. Interestingly, in ERβKO males vs females all the autosomal DEGs were lost. Gene Ontology analysis of the subset of DEGs with sex differences only in the WT cortex revealed a significant enrichment of genes annotated with the function 'cation channel activity'. Moreover, within each sex we found only a few DEGs in ERβKO vs WT mice (8 and 5 in males and females, respectively).ConclusionsOverall, our results suggest that in the adult mouse posterior cortex there are surprisingly few sex differences in gene expression, and those that exist are mainly related to cation channel activity. Additionally, they indicate that brain region-specific functional effects of ERβ may be largely post-transcriptional.

Project description:Sex differences in oxidative stress-associated cognitive decline are influenced by sex hormone levels. Notably, oxidative stress-associated neuronal cell death can be exacerbated through testosterone signaling via membrane androgen receptor AR45, which is complexed with G protein Gαq within plasma membrane-associated lipid rafts. The objective of this study was to elucidate the impact of sex on the expression of AR45 and Gαq in brain regions associated with cognitive function, specifically hippocampus subregions and entorhinal cortex. Additionally, we investigated whether chronic intermittent hypoxia (CIH), an oxidative stressor with sex-specific effects, would modulate AR45 and Gαq expression in these brain regions. Adult male and female Sprague-Dawley rats were exposed to CIH or normoxia (room air) during their sleep phase for 14 days. We quantified AR45 and Gαq protein expression in various cognition-associated brain regions [dorsal hippocampal CA1, CA3, dentate gyrus (DG), and entorhinal cortex (ETC)] via western blotting. For comparisons, AR45 and Gαq protein expression were also assessed in brain regions outside the hippocampal-ETC circuit [thalamus (TH) and striatum (STR)]. The highest AR45 levels were expressed in the hippocampal CA1 and DG while the lowest expression was observed in the extrahippocampal STR. The highest Gαq levels were expressed in the hippocampal-associated ETC while the lowest expression was observed in the extrahippocampal TH. Females expressed higher levels of AR45 in the hippocampal DG compared to males, while no sex differences in Gαq expression were observed regardless of brain region assessed. Moreover, there was no effect of CIH on AR45 or Gαq expression in any of the brain regions examined. AR45 expression was positively correlated with Gαq expression in the CA1, DG, ETC, TH, and STR in a sex-dependent manner. Our findings reveal enrichment of AR45 and Gαq protein expression within the hippocampal-ETC circuit, which is vulnerable to oxidative stress and neurodegeneration during cognitive decline. Nonetheless, CIH does not modulate the expression of AR45 or Gαq. Importantly, there are sex differences in AR45 expression and its association with Gαq expression in various brain regions, which may underlie sex-specific differences in cognitive and motor function-associated declines with aging.

Dataset Information

Sex differences in expression of oestrogen receptor ? but not androgen receptor mRNAs in the foetal lamb brain.

Publications

Sex differences in expression of oestrogen receptor α but not androgen receptor mRNAs in the foetal lamb brain.

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