{"id":619,"date":"2017-03-17T03:51:50","date_gmt":"2017-03-17T08:51:50","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=619"},"modified":"2017-03-17T03:51:50","modified_gmt":"2017-03-17T08:51:50","slug":"androgen-receptor","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/androgen-receptor\/","title":{"rendered":"Androgen Receptor"},"content":{"rendered":"

Nuclear Hormone Receptors<\/b><\/strong>
\n<\/b><\/strong>Nuclear hormone receptors are a super-family of evolutionarily conserved ligandregulated transcription factors that collectively direct genomic programs for a wide\u00a0array of biological processes including reproduction, development, metabolism,\u00a0circadian rhythm and immune response. Nuclear receptors contain six modular\u00a0regions, A-F. There are 48 genes that encode nuclear receptors in humans, and these\u00a0receptors can be subdivided into three main groups based on the nature of their\u00a0cognate ligand, which they bind with high affinity and specificity.
\nSteroid hormone receptors<\/i><\/b><\/em><\/strong>
\n<\/i><\/b><\/em><\/strong>The members of the steroid binding receptors are Glucocorticoid Receptor<\/a> (GR),\u00a0Estrogen Receptor<\/a> (ER) \u03b1 and \u03b2, Progesterone Receptor (PR), Mineralocorticoid\u00a0Receptor<\/a> (MR), and the Androgen Receptor<\/a> (AR). These receptors bind DNA as\u00a0homodimers in order to regulate transcription.
\nNon-steroid hormone receptors<\/i><\/b><\/em><\/strong>
\n<\/i><\/b><\/em><\/strong>Non-steroid binding receptors include Thyroid hormone receptors (TRs), Peroxisome\u00a0proliferator-activated receptors (PPARs), the vitamin D3 receptor (VDR), Retinoic\u00a0acid receptors (RARs), Farnesoid X Receptor (FXR) and Retinoid X receptor (RXR),\u00a0etc. Other members of this group include Liver X Receptors (LXRs), which use\u00a0oxysterols and glucose as ligands,\u00a0steroidogenic factor 1 (SF-1) and Liver receptor homolog 1 (LRH-1), which use\u00a0phospholipids as ligands, and Rev-Erbs, which were recently\u00a0shown to use heme as a ligand.
\nOrphan Receptors<\/i><\/b><\/em><\/strong>
\n<\/i><\/b><\/em><\/strong>This group of receptors contains DNA-binding transcription factors such as the Nerve
\ngrowth factor IB-like receptors Nur77\/NR4A1 and Nurr1\/NR4A2, which exhibit the
\ngeneral domain organization of nuclear receptors but whose natural ligands are not yet
\nestablished.<\/p>\n

The Androgen Receptor (AR)<\/b><\/strong>
\n<\/b><\/strong>Androgens are steroid hormones that stimulate the development and maintenance of male sex characteristics. Examples of androgens include Testosterone (T),\u00a0Dihydrotestosterone (DHT)-a key metabolite of T, and the predominant androgen\u00a0found in the prostate in vivo<\/i><\/em>, Dehydroepiandrosterone (DHEA)-a T precursor\u00a0secreted by the adrenal gland, and synthetic compounds such as methyltrienolone\u00a0(R1881).<\/p>\n

The physiological effects of androgens are mediated by the androgen receptor (AR), which functions as an androgen-regulated transcription factor. In humans, the AR\u00a0(NR3C4) gene is located on the X chromosome. Inactivating AR gene mutations in\u00a0humans, and AR gene deletion in mice result in complete androgen-insensitivity\/
\ntesticular feminization syndrome (i.e. XY <\/i><\/em>females) and infertility, and late onset\u00a0obesity in mice. AR mRNA expression in a variety of mouse tissues has been determined and shows the highest levels in tissues from the male reproductive tract (rank order of expression: epididymus > vas deferens > prostate > testes). High expression was also observed in non-reproductive tissues including kidney, adrenal gland and muscle. AR expression in humans is likely similar to that observed in mice.<\/p>\n

AR Function in Prostate Epithelial Cells and Cancer<\/i><\/b><\/em><\/strong>
\n<\/i><\/b><\/em><\/strong>Prostate cancer is described as an adenocarcinoma, because it most likely arises from the epithelial compartment. In mammals, castration\u00a0results in severe atrophy of the prostate, suggesting that androgens sustain cell survival\u00a0in the prostate. Immuno-staining of human prostate tissues showed that AR protein is\u00a0predominantly expressed in the nucleus of differentiated prostate luminal epithelial\u00a0cells that surround the lumen within the gland. In other studies\u00a0using polyclonal or monoclonal antibodies against the AR N-terminus, the basal\u00a0epithelial cells (proliferating cells located adjacent to the basal lamina) showed little to\u00a0no AR immunoreactivity in the human or rat prostate. In situ <\/i><\/em>hybridization studies on human prostate tissues detected AR mRNA in\u00a0basal cells, and RT-PCR studies detected AR mRNA in cultured proliferating human\u00a0prostate epithelial cells. Therefore, while\u00a0the AR gene is expressed in both basal and luminal epithelial cells, it is possible that\u00a0translation of AR mRNA is more efficient, or that AR protein is more stable in\u00a0luminal compared to basal cells.<\/p>\n

In normal prostate epithelial cells, AR is thought to drive luminal cell differentiation.\u00a0Prostate epithelia-specific \u201cknock-out\u201d of AR reduced expression of luminal cell\u00a0markers such as Nkx3.1 and probasin, and increased epithelial cell proliferation\u00a0detected by BrdU-incorporation, leading to hyperplasia; and these effects were\u00a0reversed by re-introduction of AR. Androgen stimulation of\u00a0proliferating human prostate epithelial cells transduced with AR in culture, reduces\u00a0expression of c-Myc and Bcl-2 (which drive cell proliferation and survival,\u00a0respectively), and leads to terminal differentiation and expression of keratins 8 and 18,\u00a0and prostate specific antigen (PSA), indicative of a luminal phenotype.<\/p>\n

In contrast, androgen stimulation results in increased proliferation of AR-positive\u00a0prostate cancer cells such as LNCaP. Prostate cancer is\u00a0primarily an androgen-dependent disease that is thought to stem from prostatic\u00a0intraepithelial neoplasia (PIN), a precursor condition indicating proliferation of\u00a0luminal epithelial cells. Aggressive prostate cancer\u00a0exhibits loss of the basal lamina and invasion of surrounding tissues by proliferating\u00a0malignant cells.<\/p>\n

 <\/p>\n

Reference:<\/h4>\n

JEROME C. NWACHUKWU. FUNCTION OF ANDROGEN RECEPTOR TRAPPED CLONE-27\u00a0IN PROSTATE CANCER CELLS<\/p>\n","protected":false},"excerpt":{"rendered":"

Nuclear Hormone Receptors Nuclear hormone receptors are a super-family of evolutionarily conserved ligandregulated transcription factors that collectively direct genomic programs for a wide\u00a0array of biological processes including reproduction, development, metabolism,\u00a0circadian […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[181],"tags":[410,407,406,409,405,403,412,408,404],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/619"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=619"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/619\/revisions"}],"predecessor-version":[{"id":620,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/619\/revisions\/620"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=619"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=619"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=619"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}