Reversing silenced AR signal with demethylating agents - A promising treatment option?

Therapeutic Efforts Pharmaceutical
#261

Good find!

AR CAG repeat polymorphism is not associated with ED complaints, gonadal steroids and sleep parameters in men from a population-based sample in Brazil.

ncbi.nlm.nih.gov/pubmed/18840639

Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats.

The AR CAG repeat length correlates significantly with serum T and estradiol of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or nearly totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions after aromatization of the higher T levels.

Alot modulates androgen expression.

#262

jcem.endojournals.org/cgi/reprint/88/9/4043

Expression and Degradation of Androgen Receptor: Mechanism and Clinical Implication.

The androgen-androgen receptor (AR) signaling pathway plays a key role in proper development and function of male reproductive organs, such as prostate and epididymis, as well as nonreproductive organs, such as muscle, hair follicles, and brain. Abnormalities in the androgen-AR signaling pathway have been linked to diseases, such as male infertility, Kennedyā€™s disease, and prostate cancer. Regulation of AR activity can be achieved in several different ways: modulation of AR gene expression, androgen binding to AR, AR nuclear translocation, AR protein stability, and AR trans-activation. This review covers mechanisms implicated in the control of AR protein expression and degradation, and their potential linkage to the androgen-related diseases. A better understanding of such mechanisms may help us to design more effective androgens and antiandrogens to battle androgen-related diseases.

Thanks Xhorndog. Iā€™m taking a break for a week or two now. Someone should read through this article. Its an important one!

#263

I know I said Iā€™m having a break but I had the thought alot of us complain of prostate pain and some of us have joint issues too. Also some people have some relief of symptoms on anti inflammatory medication or antibiotics or on the brocolli treatment.

viewtopic.php?f=5&t=4660
viewtopic.php?f=30&t=4167

circ.ahajournals.org/cgi/content/full/106/22/e185

The authors conclude that because androgens have antiinflammatory properties,2 androgenic progestins such as MPA (?) may attenuate proinflammatory effects of estrogens and may actually be responsible for the favorable effect of estrogen-progestogen combinations on inflammatory markers such as cellular adhesion molecules (ICAM-1, VCAM-1, E-selectin) and acute phase proteins (CRP and SAA) in postmenopausal women undergoing hormonal replacement therapy.

MPA is a 17-hydroxyprogesterone derivative and it is structurally related to progesterone and not testosterone.3 In addition to binding to progesterone receptor, MPA may interact with the glucocorticoid receptor.4 Progesterone and its derivatives have antiinflammatory and immunosuppressive properties that are relevant for maintenance of pregnancy.5 Because MPA is not a 19-nortestosterone derivative (androgenic progestin), its antiinflammatory properties can be attributed to its ability to interact with the progesterone and glucocorticoid receptors, not the androgen receptor.

arthritis-research.com/content/11/5/126

However, adrenal and gonadal androgens, which exert anti-inflammatory activities, are significantly decreased in inflamed tissues (that is, synovial fluid) during active RA in both male and female patients, which supports a pro-inflammatory milieu at least in RA joints (Figure 1). Interestingly, increased aromatization of androgens has been demonstrated in cultured synovial cells from RA patients and the synthesized estrogens are further converted to pro-proliferative estrogens, such as the 16-hydroxylated forms of estrone and 17Ī²-estradiol [8].

So basically androgens have an anti inflammatory function and estrogens can have a inflammatory effect. This is interesting. Lets say you increase your testosterone via TRT and the anti inflammatory function is not fulfilled properly due to androgen resistance. It is possible more testosterone is converted via aromatase - leading to a further problem.

However, that is not to say some people will not benefit on TRT. I believe some people will depending on the depth of their problem.

viewtopic.php?f=5&t=4352

However, his symptoms are not fully gone and he had fluctuations. Estrogens can mess things up - but at the same time are important in normal amounts. Taking testosterone in itself will boost estrogens. Interesting he had a gluten free diet for a while too which may help decrease androgen resistance.

Now I donā€™t believe TRT is a long term solution but whether short term pulses can help change gene expression and regulation is still up for debate. Need to read that androgen receptor article when I have more brain power.

Over and out.

#264

interesting:

endotext.org/male/male2/maleframe2.htm

Acquired androgen insensitivity may occur without AR mutations by mechanisms such as drugs including non-steroidal (flutamide, bicalutamide, nilutamide) and steroidal (cyproterone acetate), drugs that block part of testosterone activation such as 5Ī± reductase inhibitors (finasteride, dutasteride) or estrogen antagonists or aromatase inhibitors. In addition, drugs may have physiological effects or pharmacological actions that oppose various steps in androgen action such as LH and FSH suppression by estrogens or progestins or that cause an increase in circulating SHBG which may influence testosterone transfer from blood into tissues to produce a functional phenocopy of androgen insensitivity.

Acquired androgen insensitivity in various disease states is reported with hormonal findings reflecting impeded androgen action which may be reversible with alleviation of the underlying disease. The disease-related mechanisms that impede androgen action vary but the most frequent is increase in hepatic SHBG secretion due to the underlying disease and/or its drug treatments that impede androgen action by reducing testosterone transport from blood to tissues as part of its overall reduction in Ƃ metabolic clearance rate of testosterone. For example, in hyperthyroidism, increased blood LH and testosterone concentrations with clinical features of androgen deficiency 200 are mediated by increased circulating SHBG due to thyroid hormone-induced hepatic SHBG secretion 201 whereas in hypothyroidism the reduced blood testosterone and SHBG are rapidly corrected by thyroid hormone repacement therapy 200. In epilepsy, anticonvulsant-induced increase in hepatic SHBG secretion appears to be a common denominator in the near ubiquitous reproductive endocrine abnormalities in men with epilepsy 202. The relative contributions of impaired tissue transfer of testosterone, reduced testosterone metabolic clearance rate 203 or direct anti-androgenic effects of valproate 204 remain to be clarified. A similar mechanism of disease- and/or drug-induced increases in hepatic SHBG secretion may explain apparent acquired androgen insensitivity, often reversible with alleviation of the underlying disease, in various other conditions such as gluten enteropathy 205, 206, Wilsonā€™s disease 207, relapsed acute intermittent porphyria 208, acute alcoholism 209, chronic liver disease and transplantation 48, 210.

#265

I was wondering if anyone had ruled out genetic mutations for the androgen receptor?

I think its unlikely but needs to be ruled out.

#266

ncbi.nlm.nih.gov/pubmed/20353424

Tissue changes in senescent gerbil prostate after hormone deprivation leads to acquisition of androgen insensitivity.

The present study examined the response of the prostate epithelium of senescent gerbils submitted to orchiectomy and with or without steroidal blockade. Animals were divided into five groups, all surgically castrated except the control group composed of intact animals. In the experimental groups, doses of flutamide and/or tamoxifen were applied for 1, 3, 7 and 30 days postcastration. The structural methods applied reveal that castration, whether associated or not with anti-steroidal drugs, promoted short- and long-term decrease in wet and relative weights of the prostate. The quantitative decline of epithelial compartment proportion observed at the end of treatment was due to the sum of slight changes in the epithelium and lumen. The apoptotic index had risen significantly at 1 day and declined at 7 days postcastration. Androgen receptor (AR) expression decreased after 3 days of hormonal ablation, coinciding with the highest levels of apoptosis and cell proliferation observed in all treated groups. The majority of cells remained differentiated in all groups due to CK 8/18 expression. Some animals remained with injuries such as carcinomas and adenocarcinomas after hormonal ablation. In the latter a mixture of AR-positive and AR-negative cells was identified. Microinvasive carcinomas found in the group treated for 30 days consisted of PCNA-positive, inflammatory and non-proliferating cells. Low apoptosis incidence and bcl-2 positive cells were observed in these lesions. The treatments promoted a reduction of lesions in older gerbils, but treatment-resistant tumours will improve understanding of the events that lead to hormone resistance.

#267

For my reference:

clinchem.org/cgi/reprint/41/11/1617.pdf
jcem.endojournals.org/cgi/reprint/83/8/2749.pdf
jcem.endojournals.org/cgi/content/abstract/83/8/2749
jcem.endojournals.org/cgi/content/abstract/76/4/977
ncbi.nlm.nih.gov/pubmed/1386956
ncbi.nlm.nih.gov/pubmed/2972739
researchprofiles.collexis.com/ohsuv3/pubDetail.asp?t=pm&id=3335605&o_id=&n=Orwoll%2C+Eric+S&u_id=1362
eblue.org/article/0190-9622(9270064-M/abstract
ionchannels.org/showabstract.php?pmid=11500254
ncbi.nlm.nih.gov/pubmed/15721054
andrologyjournal.org/cgi/reprint/10/4/259.pdf
ncbi.nlm.nih.gov/pubmed/1551803
ncbi.nlm.nih.gov/pubmed/7540569
clinchem.org/cgi/content/full/43/11/2091

mend.endojournals.org/cgi/content/abstract/7/7/924

Autoregulation is a control mechanism common to several proteins of the steroid/thyroid hormone receptor superfamily. In this work, the effect of androgens and antiandrogens on the expression of the human androgen receptor (hAR) in prostate and breast cancer cell lines was studied. Northern blot analysis revealed a decrease in hAR steady state RNA levels in LNCaP cells by 3.3 nM of the synthetic androgen mibolerone. Maximal down-regulation of hAR RNA to 30% of control levels occurred 48 h after hormone addition. T47D breast cancer cells showed a similar effect with mibolerone, while hAR expression in normal skin fibroblasts did not respond to androgen treatment. As shown by nuclease S1 analysis, hAR transcripts initiate at three principal start sites, all of which are equally sensitive to androgen. Steroidal as well as nonsteroidal antiandrogens were capable of partially antagonizing androgen-mediated hAR RNA down-regulation in LNCaP and T47D cells, while not exerting a significant effect when administered alone. While hAR RNA stability was increased by hormone, nuclear run-on analysis revealed a 4-fold reduction of hAR gene transcription 96 h after androgen treatment. Although decreased hAR RNA levels did not coincide with a parallel decrease in AR protein levels, analysis of androgen- inducible reporter constructs demonstrated that prolonged androgen administration to cells results in a progressively impaired sensitivity of the intracellular androgen response mechanism. These results show that prolonged androgen exposure leads, besides its effect on hAR RNA levels, to functional inactivation of the AR. Thus, in vivo, posttranslational control of AR activity appears to be a novel mechanism of negative autoregulation of androgen effects on gene expression.

#268

are you using curcumin? any effects?

#269

No, sorry i meant to post about this earlier i actually came across some conflicting information about curcumin. Whilst it acts as a DNMT inhibitor it also downregulates the androgen receptor. So i decided to give it a miss.

Curcumin down-regulates AR gene expression and
activation in prostate cancer cell lines

charakinternational.com/pdfs/article5.pdf

#270

thanks man. but I was thinking to try in very small qauntity.

#271

I wouldnā€™t recommend it. The only reason for trying something like this is to see if it has a negative effect.

I once tried topical spironolactone to see if it made my symptoms worse in the same way as fin and it had similar effects. Wanted to see if the effect fin had felt similar to the anti androgen effect of spiro. It did.

I stopped it and returned to present state.

#272

ncbi.nlm.nih.gov/pubmed/16336225

Anti-epileptic drug phenytoin enhances androgen metabolism and androgen receptor expression in murine hippocampus.

Epilepsy is very often related to strong impairment of neuronal networks, particularly in the hippocampus. Previous studies of brain tissue have demonstrated that long-term administration of the anti-epileptic drug (AED) phenytoin leads to enhanced metabolism of testosterone mediated by cytochrome P450 (CYP) isoforms. Thus, we speculate that AEDs affect androgen signalling in the hippocampus. In the present study, we investigated how the AED phenytoin influences the levels of testosterone, 17beta-oestradiol, and androgen receptor (AR) in the hippocampus of male C57Bl/6J mice. Phenytoin administration led to a 61.24% decreased hippocampal testosterone level as compared with controls, while serum levels were slightly enhanced. 17beta-Oestradiol serum level was elevated 2.6-fold. Concomitantly, the testosterone metabolizing CYP isoforms CYP3A11 and CYP19 (aromatase) have been found to be induced 2.4- and 4.2-fold, respectively. CYP3A-mediated depletion of testosterone-forming 2beta-, and 6beta-hydroxytestosterone was significantly enhanced. Additionally, AR expression was increased 2-fold (mRNA) and 1.8-fold (protein), predominantly in the CA1 region. AR was shown to concentrate in nuclei of CA1 pyramidal neurons. We conclude that phenytoin affects testosterone metabolism via induction of CYP isoforms. The increased metabolism of testosterone leading to augmented androgen metabolite formation most likely led to enhanced expression of CYP19 and AR in hippocampus. Phenytoin obviously modulates the androgen signalling in the hippocampus.

#273

Some studies Oscar found - just putting all in one place

ingentaconnect.com/content/hum/endo/2005/00000026/00000001/art00001
urmc.rochester.edu/george-whipple-lab/professors-investigators/documents/HJT-13.pdf
gradworks.umi.com/14/49/1449377.html
ncbi.nlm.nih.gov/pubmed/20130388

Feel the theory is coming together. And Oscars revelation on deactivated testosterone may act as one of the missing links.

viewtopic.php?f=4&t=4674

Important too?

#274

My question simplified is thisā€¦

Can you have healthy blood levels of a certain hormone and at the same time have it deactivated (converted to a more benign compound) at a high, abnormal level possibly in the tissues and/or liver?

If so, could that be from the ā€œcrashā€ portion (negative feedback loop) of DHT flooding back into the system? Maybe you can get stuck this way perhaps?

#275

Yes that is possible.

The thing is some people respond to testosterone at supraphysiological doses. Most find it stops working after a short period. Probably due to autoregulation. Also if there is androgen resistance in the form of either increased metabolism or decreased AR expression then taking testosterone could increase estrogenā€™s and therefore the testosterone/estrogen ratio will not necessarily alter much. You can actively reduce it but this again can cause problems. Itā€™s hard to optimise hormones reliably. Best bet is to try and fight the resistance if you ask me.

Iā€™m starting to think that the liver is involved as well as a degree of androgen resistance - so increased metabolism and decreased AR expression (or disrupted AR signal). Of course I may be wrong and one may be more relevant than the other.

But I believe this is what we should test for in a lab setting. This can be done.

#276

Conditional Inactivation of Androgen Receptor Gene in the Nervous System: Effects on Male Behavioral and Neuroendocrine Responses

Testosterone (T) profoundly influences central sexual differentiation and functions. In the brain, T signals either directly through
androgen receptor (AR) or indirectly through estrogen receptor (ER) following aromatization into E2 (17-estradiol). As T, through AR, also controls peripheral male sexual differentiation, the relative contribution of central AR in T-mediated regulation of behavioral and neuroendocrine responses still remains unclear. To address this question, we generated, by using Cre-loxP technology, mice selectively lacking AR expression in the nervous system. The mutant male urogenital tract was normally developed, and mice were able to produce offspring. Nonetheless, sexual motivation and performance as well as aggressive behaviors were affected. Only a low percentage of males displayed a complete sexual behavior and offensive attacks. The latency to show masculine behaviors was increased and copulation length prolonged. Erectile activity during mating was also altered. These alterations occurred despite increased levels of T and its metabolites, and an unaffected number of ER-immunoreactive cells. Olfactory preference and neuronal activation, mapped by Fos immunoreactivity, following exposure to estrus female-soiled bedding were also normal. At comparable T levels, greater differences in masculine behaviors were observed between gonadectomized control and mutant males. AR invalidation in the nervous system also disrupted the somatotropic axis since mutant males exhibited growth retardation and decreased serum levels of insulin-like growth factor I. Our findings show that central AR is required in T-induced regulation of male-typical behaviors and gonadotrope and somato-tropic axes. This genetic model offers a unique opportunity in the understanding of ARā€™s role in cerebral functions of T.

jneurosci.org/cgi/reprint/29/14/4461.pdf

#277

Below is a summary of wiki:

The effects that androgens have on the human body ā€” virilization, masculinization, anabolism, etc. ā€” are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body [74]. Likewise, under normal circumstances, the androgen receptor itself is inactive in the cell until androgen binding occurs [3].
The following series of steps illustrates how androgens and the androgen receptor work together to produce androgenic effects

  1. Androgen enters the cell.
    Only certain organs in the body, such as the gonads and the adrenal glands, produce the androgen testosterone.
    Testosterone is converted into dihydrotestosterone, a chemically similar androgen, in cells containing the 5 alpha reductase enzyme.
    Both androgens exert their influence through binding with the androgen receptor.
  2. Androgen binds with the androgen receptor.
    The androgen receptor is expressed ubiquitously throughout the tissues of the human body.
    Before it binds with an androgen, the androgen receptor is bound to heat shock proteins.
    These heat shock proteins are released upon androgen binding.
    Androgen binding induces a stabilizing, conformational change in the androgen receptor.
    The two zinc fingers of the DNA-binding domain are exposed as a result of this new conformation.
    AR stability is thought to be aided by type II coregulators, which modulate protein folding and androgen binding, or facilitate NH2/carboxyl terminal interaction.
  3. The hormone-activated androgen receptor is phosphorylated.
    Receptor phosphorylation can occur before androgen binding, although the presence of androgen promotes hyperphosphorylation.
    The biological ramifications of receptor phosphorylation are unknown.
  4. The hormone-activated androgen receptor translocates to the nucleus.
    Nucleocytoplasmic transport is in part facilitated by an amino acid sequence on the AR called the nuclear localization signal.
    The ARā€™s nuclear localization signal is primarily encoded in the hinge region of the AR gene.
  5. Homodimerization occurs.
    Dimerization is mediated by the second (nearest the 3ā€™ end) zinc finger.
  6. DNA binding to regulatory androgen response elements occurs.
    Target genes contain (or are flanked by) transcriptional enhancer nucleotide sequences that interact with the first zinc finger.
    These areas are called androgen response elements.
  7. Coactivators are recruited by the AR.
    Type I coactivators (i.e., coregulators) are thought to influence AR transcriptional activity by facilitating DNA occupancy, chromatin remodeling, or the recruitment of general transcription factors associated with RNA polymerase II holocomplex.
  8. Target gene transcription ensues.

Where is the problem???

#278

biomedcentral.com/1471-2407/8/219

Androgen regulation of the androgen receptor coregulators

Results
Five of the coregulators (AIB1, CBP, MAK, BRCA1 and Ī²-catenin) showed more than 2-fold induction and 5 others (cyclin D1, gelsolin, prohibitin, JMJD1A, and JMJD2C) less than 2-fold induction. Overexpression of AR did not affect the expression of the coregulators alone. However, overexpression of AR enhanced the DHT-stimulated expression of MAK, BRCA1, AIB1 and CBP and reduced the level of expression of Ī²-catenin, cyclinD1 and gelsolin.

Conclusion
In conclusion, we identified 5 coactivators whose expression was induced by androgens suggesting that they could potentiate AR signaling. Overexpression of AR seems to sensitize cells for low levels of androgens.

edrv.endojournals.org/cgi/reprint/23/2/175.pdf

Androgen Receptor (AR) Coregulators: An Overview

Aberrant coregulator activity due to mutation or altered expression levels may be a contributing factor in the progression of diseases related to AR activity, such as prostate cancer. AR demonstrates distinct differences in its interaction with coregulators from other steroid receptors due to differences in the functional interaction between AR do- mains, possibly resulting in alterations in the dynamic interac- tions between coregulator complexes.

clincancerres.aacrjournals.org/content/10/3/1032.short

Expression of Androgen Receptor Coregulators in Prostate Cancer

These findings suggest that the decreased expression of PIAS1 and SRC1 could be involved in the progression of prostate cancer. In addition, gene amplification of SRC1 in one of the xenografts implies that, in some tumors, genetic alteration of SRC1 may provide a growth advantage.

ncbi.nlm.nih.gov/pubmed/15805579

Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity.

Overexpression of androgen receptors (AR) in PC-3 cell, and treatment of 5alpha-dihydrotestosterone in LNCaP cells lead to the suppression of VDR transactivation. Competition for shared coregulators between AR and VDR is one possible mechanism to explain the suppressive effect of androgen-AR signals on VDR activity. Among the AR coregulators we tested, ARA54, ARA70, supervillin, and gelsolin were found to enhance VDR transactivation. Further characterization of the interaction between ARA54 or ARA70 and VDR demonstrated a direct interaction between VDR and ARA70, but no association between ARA54 and VDR. The LXXLL motif of ARA70 is essential for interaction with VDR and partially responsible for its function as a coactivator of VDR. The suppression of VDR transactivation by AR signal was restored by overexpression of ARA70, but not ARA54. Together, ARA70 and ARA54 modulate VDR transactivation, and the competition for ARA70 mediates the suppressive effect of androgen-AR on VDR transactivation.

igitur-archive.library.uu.nl/student-theses/2010-0526-200249/UUindex.html

Proteomics of androgen receptor co-regulators in prostate cancer

The androgen receptor (AR) is a ligand-dependent transcription factor. Binding of androgens induces a conformational change and subsequently binding of the receptor to androgen receptor elements (ARE) on the genomic DNA. AR activity and specificity is additionally modulated by co-regulators that are recruited upon ligand binding. So far, the precise role of co-regulators in mediating AR function in different state in growth, aging, development and diseases is poorly understood. Furthermore, studies have shown that post-translational modification of the AR can affect AR activity. Androgen receptor is also one of the driving forces of prostate cancer. Therefore detail knowledge about the function of AR co-regulators is of urgent need. Once we know which co-regulators are essential for cancer development, one option to treat the cancer cells will be inhibition of the AR-co-regulator interaction. A designed molecule or mini-protein can be used to change the conformation of AR in the way it does not recruit that particular co-regulator/s. The inhibition of the complex formation can be later checked by native MS. Since up regulation of AR activity is likely the cause of prostate cancer, another possible method to treat prostate cancer can be via inhibition of enzyme activity inherits AR modifications such as phosphorylase. In this report we describe an efficient proteomic analysis for the identification of novel AR complexes in stroma and epithelium of normal and malignant prostate cells.

molehr.oxfordjournals.org/content/14/2/107.abstract

Hormone control and expression of androgen receptor coregulator MAGE-11 in human endometrium during the window of receptivity to embryo implantation

exp-oncology.com.ua/download/735.pdf

Prostate cancer is the second most common malignancy among males after lung cancer. The growth of prostate cancer cells depends on the presence of androgens, a group of steroid hormones that include testosterone and its more active metabolite dihydrotestosteĀ­ rone. Most prostate cancers are androgenĀ­dependent and respond to the antiandrogens or androgenĀ­deprivation therapy. However, the progression to an androgenĀ­independent stage occurs frequently. Possible mechanisms that could be involved in the developĀ­ ment of hormone resistant prostate cancer causes including androgen receptor (AR) mutations, AR amplification/over expression, interaction between AR and other growth factors, and enhanced signaling in a ligandĀ­independent manner are discussed.

#279

onlinelibrary.wiley.com/doi/10.1002/ijc.22365/abstract

Androgen receptor coregulators and their involvement in the development and progression of prostate cancer

The androgen receptor signaling axis plays an essential role in the development, function and homeostasis of male urogenital structures including the prostate gland although the mechanism by which the AR axis contributes to the initiation, progression and metastatic spread of prostate cancer remains somewhat enigmatic. A number of molecular events have been proposed to act at the level of the AR and associated coregulators to influence the natural history of prostate cancer including deregulated expression, somatic mutation, and post-translational modification. The purpose of this article is to review the evidence for deregulated expression and function of the AR and associated coactivators and corepressors and how such events might contribute to the progression of prostate cancer by controlling the selection and expression of AR targets. Ā© 2006 Wiley-Liss, Inc.

#280

edrv.endojournals.org/cgi/content/abstract/28/7/778

Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex

Androgens, acting through the androgen receptor (AR), are responsible for the development of the male phenotype during embryogenesis, the achievement of sexual maturation at puberty, and the maintenance of male reproductive function and behavior in adulthood. In addition, androgens affect a wide variety of nonreproductive tissues. Moreover, aberrant androgen action plays a critical role in multiple pathologies, including prostate cancer and androgen insensitivity syndromes. The formation of a productive AR transcriptional complex requires the functional and structural interaction of the AR with its coregulators. In the last decade, an overwhelming and ever increasing number of proteins have been proposed to possess AR coactivating or corepressing characteristics. Intriguingly, a vast diversity of functions has been ascribed to these proteins, indicating that a multitude of cellular functions and signals converge on the AR to regulate its function. The current review aims to provide an overview of the AR coregulator proteins identified to date and to propose a classification of these AR coregulator proteins according to the function(s) ascribed to them. Taken together, this approach will increase our understanding of the cellular pathways that converge on the AR to ensure an appropriate transcriptional response to androgens.

pnas.org/content/102/4/1151.full

Mutation of the androgen receptor causes oncogenic transformation of the prostate

sciencedirect.com/science?_ob=ArticleURL&_udi=B6WBK-45FK8CC-9P&_user=10&_coverDate=11%2F11%2F2000&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1621978506&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=bb80e4800fc49f4a2ca85da79398bb2c&searchtype=a

Here we demonstrate that PIAS3 is expressed in prostate cancer cells and its expression is induced in response to dihydrotestosterone (DHT) treatment. Ectopic overexpression of PIAS3 suppressed AR-mediated gene activation induced by DHT-stimulation in LNCaP cells. We provide evidence that these activities were due to direct physical interactions between PIAS3 and AR. These results indicate that PIAS3 acts as a coregulator of AR signaling pathway in prostate cancer cells.

pnas.org/content/99/2/661.full

Supervillin associates with androgen receptor and modulates its transcriptional activity

Here we present SV as an AR-interacting protein and demonstrate that SV can function as an AR coregulator by enhancing AR transactivation.