3,766 research outputs found

    Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Delta(4)-tibolone

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    Data source: Supplementary material, http://www.sciencedirect.com/science/article/pii/S0303720713004747#appd002Abstract not availableTina Bianco-Miotto, Andrew P. Trotta, Eleanor F. Need, Alice M.C. Lee, Aleksandra M. Ochnik,, Lauren Giorgio, Damien A. Leach, Erin E. Swinstead, Melissa A. O’Loughlin, Michelle R. Newman, Stephen N. Birrell, Lisa M. Butler, Jonathan M.Harris, Grant Buchana

    The Contribution of Different Androgen Receptor Domains to Receptor Dimerization and Signaling

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    The androgen receptor (AR) is a ligand-activated transcription factor of the nuclear receptor superfamily that plays a critical role in male physiology and pathology. Activated by binding of the native androgens testosterone and 5{alpha}-dihydrotestosterone, the AR regulates transcription of genes involved in the development and maintenance of male phenotype and male reproductive function as well as other tissues such as bone and muscle. Deregulation of AR signaling can cause a diverse range of clinical conditions, including the X-linked androgen insensitivity syndrome, a form of motor neuron disease known as Kennedy’s disease, and male infertility. In addition, there is now compelling evidence that the AR is involved in all stages of prostate tumorigenesis including initiation, progression, and treatment resistance. To better understand the role of AR signaling in the pathogenesis of these conditions, it is important to have a comprehensive understanding of the key determinants of AR structure and function. Binding of androgens to the AR induces receptor dimerization, facilitating DNA binding and the recruitment of cofactors and transcriptional machinery to regulate expression of target genes. Various models of dimerization have been described for the AR, the most well characterized interaction being DNA-binding domain- mediated dimerization, which is essential for the AR to bind DNA and regulate transcription. Additional AR interactions with potential to contribute to receptor dimerization include the intermolecular interaction between the AR amino terminal domain and ligand-binding domain known as the N-terminal/C-terminal interaction, and ligand-binding domain dimerization. In this review, we discuss each form of dimerization utilized by the AR to achieve transcriptional competence and highlight that dimerization through multiple domains is necessary for optimal AR signaling.Margaret M. Centenera, Jonathan M. Harris, Wayne D. Tilley and Lisa M. Butle

    Adolescent body dissatisfaction and the media

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    In this paper, an examination of the correlation between the use of sexual images in advertising and feelings of discontent with body image in adolescent girls will take place. It is this author’s opinion that the over-use of sexual images in advertising negatively effects how young girls perceive their bodies. This author’s research question examined whether the increased use of sex as an advertising tool is associated with the way that an adolescent girl perceives her own body. A literature search was also completed in which it was found that there is significant evidence to support this author’s claim. A broad internet search was done to obtain the most common keywords, and then a more in-depth search was done to find appropriate articles.M.A.L.S.Includes bibliographical referencesby Lisa M. Forber

    Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer

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    Copyright © 2007 by The Federation of American Societies for Experimental BiologyThere is now considerable evidence that using a combination of synthetic progestins and estrogens in hormone replacement therapy (HRT) increases the risk of breast cancer compared with estrogen alone. Furthermore, the World Health Organization has recently cited combination contraceptives, which contain synthetic progestins, as potentially carcinogenic to humans, particularly for increased breast cancer risk. Given the above observations and the current trend toward progestin-only contraception, it is important that we have a comprehensive understanding of how progestins act in the millions of women worldwide who regularly take these medications. While synthetic progestins, such as medroxyprogesterone acetate (MPA), which are currently used in both HRT and oral contraceptives were designed to act exclusively through the progesterone receptor, it is clear from both clinical and experimental settings that their effects may be mediated, in part, by binding to the androgen receptor (AR). Disruption of androgen action by synthetic progestins may have serious deleterious side effects in the breast, where the balance between estrogen signaling and androgen signaling plays a critical role in breast homeostasis. Here, we review the role of androgen signaling in the normal breast and in breast cancer and present new data demonstrating that androgen receptor function can be perturbed by low doses of MPA, similar to doses achieved in serum of women taking HRT. We propose that the observed excess of breast malignancies associated with combined HRT may be explained, in part, by synthetic progestins such as MPA acting as endocrine disruptors to negate the protective effects of androgen signaling in the breast. Understanding the role of androgen signaling in the breast and how this is modulated by synthetic progestins is necessary to determine how combined HRT alters breast cancer risk, and to inform the development of optimal preventive and treatment strategies for this disease.Stephen N. Birrell, Lisa M. Butler, Jonathan M. Harris, Grant Buchanan and Wayne D. Tille

    Functional Androgen Signaling in an Explant Model of Normal Human Breast Tissue.

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    Submitted abstractTheresa E. Hickey, Aleksandra Ocknik, Tina Bianco-Miotto, Steve N. Birrell, Lisa M. Butler, Wayne D. Tille

    Molecular pathology and prostate cancer therapeutics: from biology to bedside

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    Article first published online: 10 DEC 2013Abstract not availableDaniel Nava Rodrigues, Lisa M Butler, David Lorente Estelles and Johann S de Bon

    New Opportunities for Targeting the Androgen Receptor in Prostate Cancer

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    Recent genomic analyses of metastatic prostate cancer have provided important insight into adaptive changes in androgen receptor (AR) signaling that underpin resistance to androgen deprivation therapies. Novel strategies are required to circumvent these AR-mediated resistance mechanisms and thereby improve prostate cancer survival. In this review, we present a summary of AR structure and function and discuss mechanisms of AR-mediated therapy resistance that represent important areas of focus for the development of new therapies.Margaret M. Centenera, Luke A. Selth, Esmaeil Ebrahimie, Lisa M. Butler and Wayne D. Tille

    Androgenic regulation of lipid elongation in prostate cancer

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    AbstractZeyad D Nassar, Margaret M Centenera, Jelle Machiels, Samuel J Polacek, Katarzyna Bloch, Wayne D Tilley, Luke A Selth, Lisa M Butler, and Johannes V Swinne
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