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  • Author: Peng Lu x
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B Peng, B Lu, E Leygue and LC Murphy

Estrogen receptors (ERalpha and ERbeta) are clearly multifaceted in terms of structure and function. Several relatively abundant ERbeta isoforms have been identified, which can be differentially expressed in various tIssues. In order to provide insight into the possible role of the ERbeta family in breast tIssue a study of the putative functions of the human (h) ERbeta1, hERbeta2 and hERbeta5 isoforms was undertaken. Only hERbeta1 was found to bind ligand, which induced conformational changes as determined by protease digestion assays. All ERbeta isoforms could bind to and bend DNA although the relative efficiency with which they bound DNA differed with hERalpha>hERbeta1>hERbeta2>>hERbeta5. All ERbeta isoforms inhibited ERalpha transcriptional activity on an estrogen-response element (ERE)-reporter gene. The relative activities were hERbeta1>hERbeta2>hERbeta5; however, only hERbeta1 had transcriptional activity of its own. Both LY117018-hERalpha and LY117018-hERbeta1 complexes alone could activate transcription on a TGF-beta3-CAT gene. Although hERbeta2 and hERbeta5 had no activity alone, they inhibited ERalpha but not hERbeta1 transcriptional activity of transforming growth factor (TGF)-beta3-CAT. In marked contrast to activity on an ERE-CAT reporter gene, hERbeta1 did not modulate ERalpha transcriptional activity on a TGF-beta3-CAT reporter gene. These data support promoter-specific differential activities of hERbeta isoforms with respect to models of ERalpha regulated gene expression, and suggest that they may have a role in differentially modulating estrogen action.

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Qianqian Lu, Yuying Yang, Sheng Jia, Shaoqiang Zhao, Bin Gu, Peng Lu, Yang He, Ruixin Liu, Jiqiu Wang, Guang Ning and Qinyun Ma

Appetite is tightly controlled by neural and hormonal signals in animals. In general, steroid receptor coactivator 1 (SRC1) enhances steroid hormone signalling in energy balance and serves as a common coactivator of several steroid receptors, such as oestrogen and glucocorticoid receptors. However, the key roles of SRC1 in energy balance remain largely unknown. We first confirmed that SRC1 is abundantly expressed in the hypothalamic arcuate nucleus (ARC), which is a critical centre for regulating feeding and energy balance; it is further co-localised with agouti-related protein and proopiomelanocortin neurons in the arcuate nucleus. Interestingly, local SRC1 expression changes with the transition between sufficiency and deficiency of food supply. To identify its direct role in appetite regulation, we repressed SRC1 expression in the hypothalamic ARC using lentivirus shRNA and found that SRC1 deficiency significantly promoted food intake and body weight gain, particularly in mice fed with a high-fat diet. We also found the activation of the AMP-activated protein kinase (AMPK) signalling pathway due to SRC1 deficiency. Thus, our results suggest that SRC1 in the ARC regulates appetite and body weight and that AMPK signalling is involved in this process. We believe that our study results have important implications for recognising the overlapping and integrating effects of several steroid hormones/receptors on accurate appetite regulation in future studies.