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The major burden of the human immunodeficiency (HIV) type 1 pandemic is nowadays carried by women from sub-Saharan Africa. Differences in the manifestations of HIV-1 infection between women and men have been long reported, and might be due to both socio-economic (gender) and biological (sex) factors. Several studies have shown that women are more susceptible to HIV-1 acquisition than men. Following HIV-1 infection, women have lower viral loads during acute infection and exhibit stronger antiviral responses than men, which may contribute to differences in the size of viral reservoirs. Oestrogen receptor signalling could represent an important mediator of sex differences in HIV-1 reservoir size and may represent a potential therapeutic target. Furthermore, immune activation, a hallmark of HIV-1 infection, is generally higher in women than in men and could be a central mechanism in the sex difference observed in the speed of HIV-1 disease progression. Here, we review the literature regarding sex-based differences in HIV-1 infection and discuss how a better understanding of the underlying mechanisms could improve preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Regulatory crosstalk between the aryl hydrocarbon receptor (AHR) and oestrogen receptor α (ERα) is well established. Apart from the nuclear receptors ERα and ERβ, oestrogen signalling further involves an unrelated G protein-coupled receptor termed GPR30. In order to investigate potential regulatory crosstalk, this study investigated the influence of G-1 as one of the few GPR30-specific ligands on the AHR regulon in MCF-7 cells. As a well-characterised model system, these human mammary carcinoma cells co-express all three receptors (AHR, ERα and GPR30) and are thus ideally suited to study corresponding regulatory pathway interactions on transcript level. Indeed, treatment with micromolar concentrations of the GPR30-specific agonist G-1 resulted in up-regulation of AHR as well as the transcripts for cytochromes P450 1A1 and 1B1, two well-known targets of the AHR regulon. While this was partly attributable to G-1-mediated inhibition of tubulin assembly and subsequent cell cycle arrest in the G2/M phase, the effects nevertheless required functional AHR. However, G-1-induced up-regulation of CYP 1A1 was not mediated by GPR30, as G15 antagonist treatment as well as a knockdown of GPR30 and AHR failed to inhibit this effect. [ABSTRACT FROM AUTHOR]

Aims This study aimed to examine the involvement of glucose-regulated protein 94 ( GRP94) in oestrogen receptor-α36 ( ER-α36)-mediated oestrogen signalling in gastric cancer development. Methods and results A total of 130 formalin-fixed and paraffin-embedded gastric tumour samples with corresponding normal gastric and tumour-adjacent tissues were used. High levels of GRP94 expression (2+ or 3+) were observed in 109 of 130 gastric carcinomas (83.85%) by immunohistochemistry, and in 13 of 18 tumour specimens (72.22%) with Western blot analysis. GRP94 expression was correlated positively with gender, tumour stage, lymph node metastasis and ER-α36 expression ( P < 0.05). Oestrogen treatment up-regulated both GRP94 and ER-α36 expression in gastric cancer SGC7901 cells. In addition, steady state levels of GRP94 protein were decreased in established gastric cancer SGC7901 cells with knocked-down levels of ER-α36 expression and in xenograft tumours formed by these cells. Forced expression of recombinant ER-α36 in SGC7901 cells, however, up-regulated the levels of GRP94 expression. Conclusions Glucose-regulated protein 94 is a downstream effector of ER-α36-mediated oestrogen signalling, and may be involved in ER-α36 function during gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

The steroid hormone oestrogen is central to normal female physiology, reproduction and behaviour, through its effects on cellular processes including cell proliferation and cell survival. The effects of oestrogen are mediated by nuclear ERs (oestrogen receptors). ER status is important for the development, progression and treatment of breast cancer. miRNAs (microRNAs) are small non-coding RNAs that bind the 3''-UTR (untranslated region) of target mRNAs to reduce their stability and/or translation. miRNAs participate in oestrogen signalling by regulating oestrogen-responsive genes and pathways. Interestingly expression and maturation of miRNAs can also be regulated by ER signalling at multiple levels. In addition to regulating the expression of miRNAs at the transcriptional level, ER appears to be able to regulate the biogenesis of miRNAs. In the present review, we summarize recent findings on miRNA biogenesis and describe various mechanisms by which oestrogen signalling can modulate the production of miRNAs. [ABSTRACT FROM AUTHOR]

Valproate (VPA) and trichostatin A (TSA), inhibitors of zinc-dependent deacetylase activity, induce reduction in the levels of mRNA encoding oestrogen receptor-α (ERα), resulting in subsequent clearance of ERα protein from breast and ovarian cell lines. Inhibition of oestrogen signalling may account for the endocrine disorders, menstrual abnormalities, osteoporosis and weight gain that occur in a proportion of women treated with VPA for epilepsy or for bipolar mood disorder. Transcriptome profiling revealed that VPA and TSA also modulate the expression of, among others, key regulatory components of the cell cycle. Meta-analysis of genes directly responsive to oestrogen indicates that VPA and TSA have a generally antioestrogenic profile in ERα positive cells. Concomitant treatment with cycloheximide prevented most of these changes in gene expression, including downregulation of ERα mRNA, indicating that a limited number of genes signal a hyperacetylated state within cells. Three members of the NAD-dependent deacetylases, the sirtuins, are upregulated by VPA and by TSA and sirtuin activity contributes to loss of ERα expression. However, prolonged inhibition of the sirtuins by sirtinol also induces loss of ERα from cells. Mechanistically, we show that VPA invokes reversible promoter shutoff of the ERα, pS2 and cyclin D1 promoters, by inducing recruitment of methyl cytosine binding protein 2 (MeCP2) with concomitant exclusion of the maintenance methylase DNMT1. Furthermore, we demonstrate that, in the presence of VPA, local DNA methylation, deacetylation and demethylation of activated histones and recruitment of inhibitory complexes occurs on the pS2 promoter.Oncogene (2005) 24, 4894–4907. doi:10.1038/sj.onc.1208662; published online 2 May 2005 [ABSTRACT FROM AUTHOR]

Environmental exposure to nonylphenol (NP) can adversely affect human and wildlife health. A systematic review was conducted to evaluate the relationship between environmental NP exposure and cancer progression risk. Literature surveys were conducted within several international databases using appropriate keywords. A comprehensive search yielded 58 eligible studies involving a wide range of adverse effects, exposure assessment methods, study designs, and experimental models. Most studies reported that NP strongly induced breast cancer progression in intended experiments. Positive associations between NP exposure and ovarian, uterine, pituitary, and testicular cancers were also reported. Although some studies reported no relation between environmental NP exposure and tumour and/or cancer progression, NP (a known endocrine disrupting chemical) induced action mechanisms in multiple experimental models and may interfere with/hyper-activate oestrogen signalling. Secretion of oestrogen and development of reproductive tissues like breasts, uteruses, and ovaries showed strong associations with possible neoplasia (i.e., uncontrolled development of tumours and/or malignant cancers). Findings of this study are important for informing policymakers to pass legislation limiting the use of environmental contaminants such as NP before all adverse effects of exposure have been determined. • Nonylphenol (NP) as an EDC can adversely health affect human and wildlife health. • The first SR on environmental NP exposure and cancer progression risk was performed. • A comprehensive search led to identify 58 studies were selected to include in SR. • A positive association between exposure to NP and cancers progression was reported. [ABSTRACT FROM AUTHOR]

Sexual dimorphisms vary widely among species. This variation must arise through sex-specific evolutionary modifications to developmental processes. Anolis lizards vary extensively in their expression of cranial dimorphism. Compared with other Anolis species, members of the carolinensis clade have evolved relatively high levels of cranial dimorphism; males of this clade have exceptionally long faces relative to conspecific females. Developmentally, this facial length dimorphism arises through an evolutionarily novel, clade-specific strategy. Our analyses herein reveal that sex-specific regulation of the oestrogen pathway underlies evolution of this exaggerated male phenotype, rather than the androgen or insulin growth factor pathways that have long been considered the primary regulators of male-biased dimorphism among vertebrates. Our results suggest greater intricacy in the genetic mechanisms that underlie sexual dimorphisms than previously appreciated. [ABSTRACT FROM AUTHOR]

Sexual dimorphisms vary widely among species. This variation must arise through sex-specific evolutionary modifications to developmental processes. Anolis lizards vary extensively in their expression of cranial dimorphism. Compared with other Anolis species, members of the carolinensis clade have evolved relatively high levels of cranial dimorphism; males of this clade have exceptionally long faces relative to conspecific females. Developmentally, this facial length dimorphism arises through an evolutionarily novel, clade-specific strategy. Our analyses herein reveal that sex-specific regulation of the oestrogen pathway underlies evolution of this exaggerated male phenotype, rather than the androgen or insulin growth factor pathways that have long been considered the primary regulators of male-biased dimorphism among vertebrates. Our results suggest greater intricacy in the genetic mechanisms that underlie sexual dimorphisms than previously appreciated.