Molecular cell biology of androgen receptor signalling

Bennett, Nigel C.; Gardiner, Robert A.; Hooper, John D.; Johnson, David W.; Gobe, Glenda C.

doi:10.1016/j.biocel.2009.11.013

Cited by 292Prostate Cancer Treatment and ResearchEstrogen and related hormone effectsSperm and Testicular Function

Molecular cell biology of androgen receptor signalling

Bennett, Nigel C., Gardiner, Robert A., Hooper, John D., Johnson, David W., Gobe, Glenda C.·2010·The International Journal of Biochemistry & Cell Biology

DOI 10.1016/j.biocel.2009.11.013

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Abstract

The classical action of androgen receptor (AR) is to regulate gene transcriptional processes via AR nuclear translocation, response element binding and recruitment of, or crosstalk with, transcription factors. AR also utilises non-classical, non-genomic mechanisms of signal transduction. These precede gene transcription or protein synthesis, and involve steroid-induced modulation of cytoplasmic or cell membrane-bound regulatory proteins. Despite many decades of investigation, the role of AR in gene regulation of cells and tissues remains only partially characterised. AR exerts most of its effects in sex hormone-dependent tissues of the body, but the receptor is also expressed in many tissues not previously thought to be androgen sensitive. Thus it is likely that a complex, more over-arching, role for AR exists. Each AR domain co-ordinates a multitude of individual and vital roles via a diverse array of interacting partner molecules that are necessary for cellular and tissue development and maintenance. Aberrant AR activity, promoted by mutations or binding partner misregulation, can present as many clinical manifestations including androgen insensitivity syndrome and prostate cancer. In the case of malignant prostate cancer, treatment generally revolves around androgen deprivation therapies designed to interfere with AR action and the androgen signalling axis. Androgen therapies for prostate cancer often fail, highlighting a real need for increased research into AR function.

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Androgen transmits signals via cell membrane receptors that are distinct from the androgen nuclear receptors.
“Androgen transmits signals via cell membrane receptors [19], which are distinct from the androgen nuclear receptors [20].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [20]

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Androgen Receptor Nuclear Translocation Is Facilitated by the f-Actin Cross-Linking Protein Filamin
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Minireview: The Contribution of Different Androgen Receptor Domains to Receptor Dimerization and Signaling
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Caveolae, transmembrane signalling and cellular transformation
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Molecular Biology of the Androgen Receptor: From Molecular Understanding to the Clinic
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Inhibiting Proteasomes in Human HepG2 and LNCaP Cells Increases Endogenous Androgen Receptor Levels
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Prostate Volume and Growth in Testosterone-Substituted Hypogonadal Men Are Dependent on the CAG Repeat Polymorphism of the Androgen Receptor Gene: A Longitudinal Pharmacogenetic Study
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Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells
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C-terminal Hsp-interacting protein slows androgen receptor synthesis and reduces its rate of degradation
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Androgen Receptor Coregulators in Prostate Cancer
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Effect of a short CAG (glutamine) repeat on human androgen receptor function
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Phosphoinositide 3-Kinase-independent Non-genomic Signals Transit from the Androgen Receptor to Akt1 in Membrane Raft Microdomains
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Complications of androgen deprivation therapy for prostate cancer
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The androgen receptor gene and its influence on the development and progression of prostate cancer
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Mechanisms of androgen receptor signalling via steroid receptor coactivator-1 in prostate.
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An Additional Region of Coactivator GRIP1 Required for Interaction with the Hormone-binding Domains of a Subset of Nuclear Receptors
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Forskolin-Induced Dephosphorylation of the Androgen Receptor Impairs Ligand Binding
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Selective role of an NH2-terminal WxxLF motif for aberrant androgen receptor activation in androgen depletion-independent prostate cancer cells.
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Androgen receptor corepressors and prostate cancer
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Early Metazoan Divergence Was About 830 Million Years Ago
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A 90 kDa fragment of filamin A promotes Casodex-induced growth inhibition in Casodex-resistant androgen receptor positive C4-2 prostate cancer cells
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Characterization of the Two Coactivator-interacting Surfaces of the Androgen Receptor and Their Relative Role in Transcriptional Control*
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The Cochaperone Bag-1L Enhances Androgen Receptor Action via Interaction with the NH2-Terminal Region of the Receptor
Shatkina, L., Mink, S., Rogatsch, H., Klocker, H., Langer, G., Nestl, A., & Cato, A. C. B. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.20.7189-7197.2003 · Cited by 78 · see citing works
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Androgen Receptor Remains Critical for Cell-Cycle Progression in Androgen-Independent CWR22 Prostate Cancer Cells
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Androgen receptor CAG polymorphism and prostate cancer risk
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Androgen Receptors in the Brain: What Are We Measuring?*
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Vertebrate Sex Steroid Receptors: Evolution, Ligands, and Neurodistribution
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Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis
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Reflections on the Diseases Linked to Mutations of the Androgen Receptor
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Antiandrogens fail to block androstenedione‐mediated mutated androgen receptor transactivation in human prostate cancer cells
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Transcriptional control within the three-dimensional context of nuclear architecture: Requirements for boundaries and direction
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Androgens, ageing and vascular function
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Unresolved
Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone
Culig (1993) · Mol Endocrinol
Unresolved
Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor
Culig (1994) · Cancer Res
Unresolved
Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers
Glass (1994) · Endocr Rev
Unresolved
Gottlieb DB. The androgen receptor gene mutations database world wide web server. Retrieved 27/9/09, from http://androgendb.mcgill.ca/; 2008.
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Unresolved
Phylogeny of vertebrate nuclear receptors—analysis of variance components in protein sequences
Gurel (2003) · Coll Antropol
Unresolved
Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate
Huggins (1941) · Cancer Res
Unresolved
Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia
Koivisto (1999) · Clin Cancer Res
Unresolved
Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity
Kousteni (2001) · Cell
Unresolved
Abnormal Leydig cell development at puberty in the androgen-resistant Tfm mouse
Murphy (1994) · Endocrinology
Unresolved
Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence
Tilley (1996) · Clin Cancer Res
Unresolved
HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway
Wen (2000) · Cancer Res
Unresolved
Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer cells
Zhuang (2002) · Cancer Res
Unresolved

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Sex differences in the hypothalamic–pituitary–adrenal axis’ response to stress: an important role for gonadal hormones
Heck, A., & Handa, R. J. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0167-9 · Cited by 532 · see citing works
Sex differences in anxiety and depression: Role of testosterone
McHenry, J. A., Carrier, N., Hull, E. M., & Kabbaj, M. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.09.001 · Cited by 505 · see citing works
“More detailed information regarding the molecular mechanisms of androgens and estrogens at their receptors can be found in Bennett et al. (2010).”
Background
Sex differences and sex steroids in lung health and disease
Townsend, E. A., Miller, V. M., & Prakash, Y. S. (2012) · Endocrine Reviews · doi:10.1210/er.2010-0031 · Cited by 395 · see citing works
Androgen-Induced Immunosuppression
Bupp, M. G., & Jørgensen, T. N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00794 · Cited by 393 · see citing works
“Activation of non-classical (NC) AR rapidly affects the regulation of other nuclear receptors, transcription factors, and cytoplasmic signaling events including the release of intracellular calcium and the formation of inositol 1,4,5-triphosphate (15).”
Background
Sex, the aging immune system, and chronic disease
Bupp, M. G. (2015) · Cellular Immunology · doi:10.1016/j.cellimm.2015.02.002 · Cited by 333 · see citing works
“Peripheral T and B cells, thymocytes, bone marrow stromal cells, thymic epithelial cells, macrophages, monocytes, dendritic cells, and mast cells express intracellular androgen receptors and peripheral T cells and circulating monocytes also express membrane-bound ARs [45–48].”
Background
On the functional diversity of glyceraldehyde-3-phosphate dehydrogenase: Biochemical mechanisms and regulatory control
Sirover, M. A. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.05.010 · Cited by 326 · see citing works
Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications
Ostrovidov, S., Hosseini, V., Ahadian, S., Fujie, T., Parthiban, S. P., Ramalingam, M., Bae, H., Kaji, H., & Khademhosseini, A. (2014) · Tissue Engineering Part B: Reviews · doi:10.1089/ten.teb.2013.0534 · Cited by 302 · see citing works
Androgen receptor roles in spermatogenesis and infertility
O’Hara, L., & Smith, L. B. (2015) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2015.04.006 · Cited by 249 · see citing works
Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms
Mahmoud, R., Wainwright, S. R., & Galea, L. A. M. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.03.002 · Cited by 201 · see citing works
“…(AR), which is classically expressed in the cytoplasm then, when bound by either testosterone or the higher-affinity DHT, translocates to the nucleus and functions as a transcription factor to directly regulate gene expression via AR binding domains (Heinlein and Chang, 2002; Bennett et al., 2010).”
Background
Sex steroid signaling: Implications for lung diseases
Sathish, V., Martin, Y. N., & Prakash, Y. S. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.01.007 · Cited by 168 · see citing works
Disruption of androgen receptor signaling in males by environmental chemicals
Luccio-Camelo, D., & Prins, G. S. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.04.004 · Cited by 169 · see citing works
Influence of Androgens on Immunity to Self and Foreign: Effects on Immunity and Cancer
Ben-Batalla, I., Vargas-Delgado, M. E., von Amsberg, G., Janning, M., & Loges, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01184 · Cited by 149 · see citing works
“Non-classical receptors can also be associated to Gproteins in the plasma membrane (22, 23).”
Background
Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer
Lamont, K. R., & Tindall, D. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0469 · Cited by 150 · see citing works
A longitudinal study: changes in cortical thickness and surface area during pubertal maturation
Herting, M. M., Gautam, P., Spielberg, J. M., Dahl, R. E., & Sowell, E. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119774 · Cited by 142 · see citing works
“Furthermore, physical changes during puberty may also, at the cellular level, reflect the sensitivity of an individual to hormone exposure as determined by genetic variations in hormone receptors [48].”
Background
An overview of transcriptional regulation in response to toxicological insult
Jennings, P., Limonciel, A., Felice, L., & Leonard, M. O. (2012) · Archives of Toxicology · doi:10.1007/s00204-012-0919-y · Cited by 144 · see citing works
“1 (Bennett et al. 2010; Yin et al. 2012).”
Sex hormone activity in alcohol addiction: Integrating organizational and activational effects
Lenz, B., Müller, C. P., Stoessel, C., Sperling, W., Biermann, T., Hillemacher, T., Bleich, S., & Kornhuber, J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.11.001 · Cited by 136 · see citing works
“regulate the activity of different kinases and control the phosphorylation of intracellular proteins, influencing their molecular activity (Bennett et al., 2010).”
Background
Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications
Lucas-Herald, A. K., Alves-Lopes, R., Montezano, A. C. I., Ahmed, S. F., & Touyz, R. M. (2017) · Clinical Science · doi:10.1042/cs20170090 · Cited by 132 · see citing works
“Testosterone Cardiac myocytes ↑ Release Ca2 + from endoplasmic reticulum and mitochondria Bennett et al. (2010) [41] Foradori et al.”
Background
Molecular and cellular mechanisms of castration resistant prostate cancer (Review)
Huang, Y., Jiang, X., Liang, X., & Jiang, G. (2018) · Oncology Letters · doi:10.3892/ol.2018.8123 · Cited by 130 · see citing works
Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles
Hoang, D. T., Iczkowski, K. A., Kilari, D., See, W. A., & Nevalainen, M. T. (2016) · Oncotarget · doi:10.18632/oncotarget.12554 · Cited by 128 · see citing works
“Binding of androgen ligands, such as testosterone and the more potent dihydrotestosterone (DHT), induces a conformational change in AR that allows for nuclear translocation and induction of androgen-responsive gene expression supporting growth and viability of prostate cells (reviewed in [32-36]).”
Background
Contributions of sex to cerebrovascular function and pathology
Robison, L. S., Gannon, O. J., Salinero, A. E., & Zuloaga, K. L. (2018) · Brain Research · doi:10.1016/j.brainres.2018.12.030 · Cited by 124 · see citing works
Molecular Alterations during Progression of Prostate Cancer to Androgen Independence
Saraon, P., Jarvi, K. A., & Diamandis, E. P. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.165977 · Cited by 115 · see citing works
In vitro model systems to study androgen receptor signaling in prostate cancer
Sampson, N., Neuwirt, H., Puhr, M., Klocker, H., & Eder, I. E. (2013) · Endocrine Related Cancer · doi:10.1530/erc-12-0401 · Cited by 105 · see citing works
Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases
Mahmud, A. R., Ema, T. I., Siddiquee, M. F. R., Shahriar, A., Ahmed, H., Mosfeq-Ul-Hasan, M., Rahman, N., Islam, R., Uddin, M. R., & Mizan, M. F. R. (2023) · Beni-Suef University Journal of Basic and Applied Sciences · doi:10.1186/s43088-023-00387-4 · Cited by 106 · see citing works
“Tight regulation of the AR signaling homeostasis is critical to maintaining diverse cell functions because dysregulation of this homeostasis leads to aberrant androgen responses and promotes prostate cancer [13].”
Background
Paxillin mediates extranuclear and intranuclear signaling in prostate cancer proliferation
Sen, A., Castro, I. D., DeFranco, D. B., Deng, F.-M., Melamed, J., Kapur, P., Raj, G. V., Rossi, R. M., & Hammes, S. R. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62044 · Cited by 103 · see citing works
Plant Microbiome Engineering: Hopes or Hypes
Afridi, M. S., Ali, S., Salam, A., Terra, W. C., Hafeez, A., Sumaira, S., Ali, B., AlTami, M. S., Ameén, F., Erċışlı, S., et al. (2022) · Biology · doi:10.3390/biology11121782 · Cited by 101 · see citing works
Molecular biology of androgen insensitivity
Jääskeläinen, J. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.08.006 · Cited by 98 · see citing works
“1) (Bennett et al., 2010).”
Influential
Neuroendocrine-immune interaction: Evolutionarily conserved mechanisms that maintain allostasis in an ever-changing environment
Kemenade, B. M. L. V.-V., Cohen, N., & Chadzińska, M. (2016) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2016.05.015 · Cited by 96 · see citing works
“The effects of androgens are mediated through classical intracellular androgen receptor (AR) and a membrane-bound AR (GPRC6A) (Bennett et al., 2010; Rahman and Christian, 2007).”
Background
Testosterone and its metabolites--modulators of brain functions.
Durdiaková, J., Ostatníková, D., & Celec, P. (2011) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2011-1863 · Cited by 94 · see citing works
Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses
Zuloaga, D. G., Heck, A., Guzman, R. M. D., & Handa, R. J. (2020) · Biology of Sex Differences · doi:10.1186/s13293-020-00319-2 · Cited by 96 · see citing works
Sexual dimorphism and the role of estrogen in the immune microenvironment of liver metastases
Milette, S., Hashimoto, M., Perrino, S., Qi, S., Chen, M., Ham, B., Wang, N., Istomine, R., Lowy, A. M., Piccirillo, C. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13571-x · Cited by 86 · see citing works
Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men
Gharahdaghi, N., Rudrappa, S. S., Brook, M. S., IDRIS, I. R., Crossland, H., Hamrock, C., Aziz, M. H. A., Kadi, F., Tarum, J., Greenhaff, P. L., et al. (2019) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12472 · Cited by 82 · see citing works
“Consistently, there is a general blunted activation of mTORc1,(71) ERK1/2,(70) and MAPKs(70) presumably due to lesser bioavailability of T.(64,72) In support of this, T therapy augmented IGF-1/Akt/mTOR signalling activity (which regulates MPS(64)), presumably explaining enhanced mass and functional gains and suggestin…”
Background
Sirtuin 1 (SIRT1) and steroid hormone receptor activity in cancer
Moore, R. L., Dai, Y., & Faller, D. V. (2011) · Journal of Endocrinology · doi:10.1530/joe-11-0217 · Cited by 81 · see citing works
“Prostate cancers also inevitably undergo an evolution from hormone responsive to hormone independent (castration-resistant cancer), although loss of AR expression is rare (Scher et al. 2004, Bennett et al. 2010, Risbridger et al. 2010).”
AZD3514: A Small Molecule That Modulates Androgen Receptor Signaling and Function In Vitro and In Vivo
Loddick, S. A., Ross, S. J., Thomason, A. G., Robinson, D. M., Walker, G. E., Dunkley, T. P. J., Brave, S. R., Broadbent, N., Stratton, N. C., Trueman, D., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-1174 · Cited by 79 · see citing works
“In the nucleus, AR binds to androgen response elements (AREs) within regulatory elements of target genes (such as prostate specific antigen (PSA) and TMPRSS2) and regulates gene expression through the recruitment of co-factors (5-7).”
Background
Mechanisms of Androgen-Independent Prostate Cancer.
Saraon, P., Drabovich, A. P., Jarvi, K. A., & Diamandis, E. P. (2014) · PubMed Central · Cited by 74 · see citing works
Regulation of masculinization: androgen signalling for external genitalia development
Matsushita, S., Suzuki, K., Murashima, A., Kajioka, D., Acebedo, A. R., Miyagawa, S., Haraguchi, R., Ogino, Y., & Yamada, G. (2018) · Nature Reviews Urology · doi:10.1038/s41585-018-0008-y · Cited by 72 · see citing works
Effects and mechanisms of pyrethroids on male reproductive system
Wang, Q., Shen, J., Zhang, R., Hong, J., Li, Z., Ding, Z., Wang, H.-X., Zhang, J., Zhang, M., & Xu, L. (2020) · Toxicology · doi:10.1016/j.tox.2020.152460 · Cited by 70 · see citing works
Dysregulation of Signaling Pathways Due to Differentially Expressed Genes From the B-Cell Transcriptomes of Systemic Lupus Erythematosus Patients – A Bioinformatics Approach
Kumar, S. U., Kumar, D. T., Ramamoorthy, S., Doss, C. G. P., Younes, S. N., Younes, N., Sidenna, M., & Zayed, H. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00276 · Cited by 71 · see citing works
Disruption of the blood-brain barrier and its close environment following adult exposure to low doses of di(2-ethylhexyl)phthalate alone or in an environmental phthalate mixture in male mice
Ahmadpour, D., Mhaouty-Kodja, S., & Grange-Messent, V. (2021) · Chemosphere · doi:10.1016/j.chemosphere.2021.131013 · Cited by 68 · see citing works
Targeting molecular resistance in castration-resistant prostate cancer
Chandrasekar, T., Yang, J. C., Gao, A. C., & Evans, C. P. (2015) · BMC Medicine · doi:10.1186/s12916-015-0457-6 · Cited by 66 · see citing works
“Androgens, specifically testosterone, the primary circulating androgen produced mainly in the Leydig cells in the testis and minimally in the adrenal cortex, and dihydrotestosterone (DHT), are the major ligands for AR. DHT, which is formed by 5α-reductase activity on testosterone within the cytoplasm, is the main func…”
BackgroundInfluential
AR-V7 in Metastatic Prostate Cancer: A Strategy beyond Redemption
Sobhani, N., Neeli, P. K., D’Angelo, A., Pittacolo, M., Sirico, M., Galli, I. C., Roviello, G., & Nesi, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115515 · Cited by 66 · see citing works
“The canonical AR gene, located on the X chromosome (Xq11‐12), exceeds 90 kb and contains eight exons encoding the AR protein, a ligand‐dependent nuclear transcription factor and member of the steroid hormone receptor family [56].”
Background
The role of testosterone, the androgen receptor, and hypothalamic-pituitary–gonadal axis in depression in ageing Men
Hauger, R. L., Saelzler, U. G., Pagadala, M. S., & Panizzon, M. S. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-022-09767-0 · Cited by 68 · see citing works
“Prior to ligand activation, the androgen receptor is sequestered in the cytoplasm where AR is stabilized by heat shock proteins and associated with cytoskeletal proteins and other chaperones [88, 89, 94].”
Background
The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells
Kretzschmar, K., Cottle, D. L., Schweiger, P. J., & Watt, F. M. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.242 · Cited by 66 · see citing works
“Although in some bulb cells the AR appeared to be concentrated at the cell periphery, the AR is not reported to have a plasma membrane localisation (Bennett et al ., 2010).”
Testosterone-induced upregulation of miRNAs in the female mouse liver
Delić, D., Großer, C., Dkhil, M. A., Al‐Quraishy, S., & Wunderlich, F. T. (2010) · Steroids · doi:10.1016/j.steroids.2010.06.010 · Cited by 63 · see citing works
How the love of muscle can break a heart: Impact of anabolic androgenic steroids on skeletal muscle hypertrophy, metabolic and cardiovascular health
McCullough, D., Webb, R., Enright, K. J., Lane, K. E., McVeigh, J., Stewart, C. E., & Davies, I. G. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-020-09616-y · Cited by 62 · see citing works
“The androgen/AR complex regulates gene transcription on the androgen response element (ARE) of DNA.”
BackgroundInfluential
G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone
Zhao, X.-F. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00620-y · Cited by 60 · see citing works
Synthetic Androgens as Designer Supplements
Joseph, J. F., & Parr, M. K. (2014) · Current Neuropharmacology · doi:10.2174/1570159x13666141210224756 · Cited by 60 · see citing works
“affecting intracellular Ca levels or allosteric modulation of GABAA receptors are discussed [18, 31-33].”
Background
Aquatic toxicity, ecological effects, human exposure pathways and health risk assessment of liquid crystal monomers
He, W., Cui, Y., Yang, H., et al. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2023.132681 · Cited by 59 · see citing works
The Effects of Androgens on T Cells: Clues to Female Predominance in Autoimmune Liver Diseases?
Henze, L., Schwinge, D., & Schramm, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01567 · Cited by 58 · see citing works
“AR can also be posttranslationally modified through phosphorylation, methylation, or ubiquitination, allowing for ligand-independent modulation of signaling (27, 29, 30).”
Background
Identification of androgen-regulated genes in human prostate
Vaarala, M. H., Hirvikoski, P. P., Kauppila, S., & Paavonen, T. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.956 · Cited by 55 · see citing works
“The activity of androgens is mediated mainly via the androgen receptor (AR), although other androgen responsive activation mechanisms may exist, especially in hormone-refractory prostate cancer (1).”
Background
Structural Diversity of Ligand-Binding Androgen Receptors Revealed by Microsecond Long Molecular Dynamics Simulations and Enhanced Sampling
Duan, M., Liu, N., Zhou, W., Li, D., Yang, M., & Hou, T. (2016) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6b00424 · Cited by 56 · see citing works
A Tale of Two Signals: AR and WNT in Development and Tumorigenesis of Prostate and Mammary Gland
Pakula, H., Xiang, D., & Li, Z. (2017) · Cancers · doi:10.3390/cancers9020014 · Cited by 52 · see citing works
“Precisely, AR is phosphorylated at serine residues (Ser80, Ser93 and Ser641) that are believed to function by protecting AR from proteolytic degradation [196,198].”
Background
Loss of Cyp11c1 causes delayed spermatogenesis due to the absence of 11-ketotestosterone
Zheng, Q., Xiao, H., Shi, H., et al. (2020) · Journal of Endocrinology · doi:10.1530/joe-19-0438 · Cited by 52 · see citing works
Transcriptome and Functional Profile of Cardiac Myocytes Is Influenced by Biological Sex
Trexler, C. L., Odell, A. T., Jeong, M. Y., Dowell, R. D., & Leinwand, L. A. (2017) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.117.001770 · Cited by 51 · see citing works
RISING STARS: androgens and immune cell function
Ainslie, R. J., Simitsidellis, I., Kirkwood, P. M., & Gibson, D. A. (2024) · Journal of Endocrinology · doi:10.1530/joe-23-0398 · Cited by 48 · see citing works
Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer
Harris, A. E., Metzler, V. M., Lothion‐Roy, J. H., Varun, D., Woodcock, C. L., Haigh, D. B., Endeley, C., Haque, M., Toss, M. S., Alsaleem, M. A., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1006101 · Cited by 47 · see citing works
“Immunotherapies and DNA repair targeted therapies: Precision medicine in practice?”
BackgroundInfluential
Testosterone Therapy in Adolescent Boys: The Need for a Structured Approach
Stancampiano, M. R., Lucas-Herald, A. K., Russo, G., Rogol, A. D., & Ahmed, S. F. (2019) · Hormone Research in Paediatrics · doi:10.1159/000504670 · Cited by 48 · see citing works
Androgens and stroke: Good, bad or indifferent?
Quillinan, N., Deng, G., Grewal, H., & Herson, P. S. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.02.004 · Cited by 47 · see citing works
“Canonical androgen signaling involves androgen binding to cytoplasmic androgen receptors, translocation to the nucleus and transcription of androgen responsive genes (for review see (Bennett et al., 2010)).”
Background
Lentiviral vector‐mediated insertional mutagenesis screen identifies genes that influence androgen independent prostate cancer progression and predict clinical outcome
Nalla, A. K., Williams, T. F., Collins, C. P., Rae, D. T., & Trobridge, G. D. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22425 · Cited by 45 · see citing works
Targeting rapid action of sex steroid receptors in breast and prostate cancers
Giovannelli, P. (2011) · Frontiers in bioscience · doi:10.2741/3849 · Cited by 44 · see citing works
The effects of urolithins on the response of prostate cancer cells to non-steroidal antiandrogen bicalutamide
Stanisławska, I. J., Piwowarski, J. P., Granica, S., & Kiss, A. K. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.03.054 · Cited by 44 · see citing works
Molecular Dynamics Simulations Revealed the Regulation of Ligands to the Interactions between Androgen Receptor and Its Coactivator
Liu, N., Zhou, W., Guo, Y., Wang, J., Fu, W., Sun, H., Li, D., Duan, M., & Hou, T. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00283 · Cited by 44 · see citing works
Seasonal changes in the expression of the androgen receptor in the testes of the domestic goose (Anser anser f. domestica)
Leska, A., Kieżun, J., Kamińska, B., et al. (2012) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2012.07.026 · Cited by 42 · see citing works
Mechanisms of sex hormones in autoimmunity: focus on EAE
Lasrado, N., Jia, T., Massilamany, C., Franco, R., Illés, Z., & Reddy, J. (2020) · Biology of Sex Differences · doi:10.1186/s13293-020-00325-4 · Cited by 44 · see citing works
“Biochemical mechanisms of sex hormones Sex hormones mediate their cellular functions through both the genomic/nuclear and nongenomic/membrane signaling pathways, with the expected end result being transcriptional regulation [140, 141] that may affect cell proliferation or cell death [142–144].”
Background
Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders
Dai, D., Li, Q., Zhu, Q., Hu, S., Balesar, R. A., Swaab, D. F., & Bao, A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.76 · Cited by 41 · see citing works
“Altogether with previous findings that these two bands may combine with other nuclear compounds acting as AR co-regulator (Bennett et al, 2010), our data indicated that site A probably represents a functional ARE.”
Background
Effects of HO-/MeO-PBDEs on Androgen Receptor: In Vitro Investigation and Helix 12-Involved MD Simulation
Wang, X., Yang, H., Hu, X., et al. (2013) · Environmental Science & Technology · doi:10.1021/es4029364 · Cited by 40 · see citing works
Anti-androgenic effects of flavonols in prostate cancer
Boam, T. (2015) · ecancermedicalscience · doi:10.3332/ecancer.2015.585 · Cited by 45 · see citing works
“The AR-signalling pathway is essential for maintaining normal metabolic function, cell proliferation, and homeostasis [23] and is an important component in the early pathogenesis of PCa.”
Sex hormone regulation of innate lymphoid cells
Blanquart, E., Laffont, S., & Guéry, J. (2020) · Biomedical Journal · doi:10.1016/j.bj.2020.11.007 · Cited by 38 · see citing works
“Besides these ligand-dependent pathways, ERa and AR can be regulated by others signals such as cytokines like IL-6 or growth factors like EGF (Epidermal growth factors) [34,37].”
Background
Intracrine and Myotrophic Roles of 5α-Reductase and Androgens
Yarrow, J. F., McCoy, S. C., & Borst, S. E. (2011) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31823bfcbf · Cited by 38 · see citing works
“One such pathway involves androgen signaling, which occurs via classic genomic-mediated protein translation after cytosolic androgen receptor (AR) activation (19) or via newly recognized rapid nongenomic receptor-mediated pathways (11,25,48).”
Background
Activity-Based Physical Rehabilitation with Adjuvant Testosterone to Promote Neuromuscular Recovery after Spinal Cord Injury
Otzel, D. M., Lee, J., Ye, F., Borst, S. E., & Yarrow, J. F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061701 · Cited by 39 · see citing works
“Classical androgen-mediated genomic signaling is initiated by the binding of T or DHT to cytosolic ARs to form hormone-receptor complexes that translocate to the nucleus and bind androgen response elements (AREs) [106], resulting in the activation or repression of multiple gene pathways that regulate skeletal muscle […”
Background
Sex steroid hormone modulation of neural stem cells: a critical review
Bramble, M. S., Vashist, N., & Vilain, E. J. N. (2019) · Biology of Sex Differences · doi:10.1186/s13293-019-0242-x · Cited by 37 · see citing works
“Whether these effects are activational or organizational could be modulated either by direct testosterone action on the androgen receptor (AR) [33] or estrogen signaling, through its various receptors (ERα, ERβ, GPR30) once locally converted into estradiol by aromatase [34].”
Y It Matters—Sex Differences in Fetal Lung Development
Laube, M., & Thome, U. H. (2022) · Biomolecules · doi:10.3390/biom12030437 · Cited by 37 · see citing works
“ERs can act as homo- or heterodimers, and ER-α can also heterodimerize with the androgen receptor (AR) resulting in a modified transcriptional activity [69].”
BackgroundInfluential
Evidence for Steroidogenic Potential in Human Prostate Cell Lines and Tissues
Bennett, N. J., Hooper, J. D., Lambie, D., Lee, C. S., Yang, T., Vesey, D. A., Samaratunga, H., Johnson, D. W., & Gobe, G. C. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.06.009 · Cited by 37 · see citing works
Self-citation
The role of transcription factors in prostate cancer and potential for future RNA interference therapy
Fitzgerald, K. A., Evans, J. C., McCarthy, J., Guo, J., Prencipe, M., Kearney, M., Watson, R. W. G., & O’Driscoll, C. M. (2014) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2014.896904 · Cited by 36 · see citing works
“Such medicines, as outlined in Figure 1, include gonadotropin-releasing hormone (GnRH) analogues and androgen receptor (AR) antagonists and aim to reduce the growth of prostate cancer cells induced by androgens normally present in the circulation [6].”
SGK3 is an androgen-inducible kinase promoting prostate cancer cell proliferation through activation of p70 S6 kinase and up-regulation of cyclin D1.
Wang, Y.-Z., Zhou, D.-J., & Chen, S. (2014) · Molecular Endocrinology · doi:10.1210/me.2013-1339 · Cited by 35 · see citing works
Testosterone-induced permanent changes of hepatic gene expression in female mice sustained during Plasmodium chabaudi malaria infection
Delić, D., Gailus, N., Vohr, H.-W., Dkhil, M. A., Al‐Quraishy, S., & Wunderlich, F. T. (2010) · Journal of Molecular Endocrinology · doi:10.1677/jme-10-0026 · Cited by 34 · see citing works
“2008, Bennett et al .”
Roles of Testosterone Replacement in Cardiac Ischemia–Reperfusion Injury
Pongkan, W., Chattipakorn, S. C., & Chattipakorn, N. (2015) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248415587977 · Cited by 34 · see citing works
“These findings suggest that endogenous testosterone may also act via other mechanisms instead of just the genomic effect on cardiac function during I/R injury.(38,89) This could be due to the nongenomic effects that are similar to other steroids,(89) which could bind to specific membrane binding sites and stimulate th…”
Background
Sex-specific differences in organic anion transporting polypeptide 1a4 (Oatp1a4) functional expression at the blood–brain barrier in Sprague–Dawley rats
Brzica, H., Abdullahi, W., Reilly, B. G., & Ronaldson, P. T. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0110-9 · Cited by 33 · see citing works
The role of the p90 ribosomal S6 kinase family in prostate cancer progression and therapy resistance
Cronin, R., Brooke, G. N., & Prischi, F. (2021) · Oncogene · doi:10.1038/s41388-021-01810-9 · Cited by 32 · see citing works
“The AR-ligand complex translocates into the nucleus, where it binds AREs [19].”
Background
Androgens and Androgen Receptors as Determinants of Vascular Sex Differences Across the Lifespan
Lucas-Herald, A. K., & Touyz, R. M. (2022) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2022.09.018 · Cited by 34 · see citing works
Interaction of APOE genotype and testosterone on episodic memory in middle-aged men
Panizzon, M. S., Hauger, R. L., Xian, H., Vuoksimaa, E., Spoon, K. M., Mendoza, S. P., Jacobson, K. C., Vasilopoulos, T., Rana, B. K., McKenzie, R. E., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.12.025 · Cited by 33 · see citing works
“The androgen receptor functions as a transcriptional activator, regulating the expression of downstream androgen-responsive genes like APOE (Bennett et al., 2010; Dalton and Gao, 2010; Raber, 2004).”
Background
Deficits in Spermatogenesis but not Neurogenesis are Alleviated by Chronic Testosterone Therapy in R6/1 Huntington’s Disease Mice
Hannan, A. J., & Ransome, M. I. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02238.x · Cited by 32 · see citing works
Testosterone-Dependent Interaction between Androgen Receptor and Aryl Hydrocarbon Receptor Induces Liver Receptor Homolog 1 Expression in Rat Granulosa Cells
Wu, Y.-G., Baumgarten, S. C., Zhou, P., & Stocco, C. O. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00011-13 · Cited by 31 · see citing works
“Cofactor recruitment is a crucial regulatory step in AR signal transduction and function (49, 50).”
Background
Sex-Steroid Signaling in Lung Diseases and Inflammation
Ambhore, N. S., Kalidhindi, R. S. R., & Sathish, V. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-63046-1_14 · Cited by 30 · see citing works
Isorhapontigenin induced cell growth inhibition and apoptosis by targeting EGFR‐related pathways in prostate cancer
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Authors: Bennett, N. C., Gardiner, R. A., Hooper, J. D., Johnson, D. W., & Gobe, G. C.
Affiliations: The University of Queensland (AU)
Queensland University of Technology (AU)
Princess Alexandra Hospital (AU)
Corresponding author: Gobe, Glenda C.
ORCID: Gardiner, Robert A.
Hooper, John D.
Johnson, David W.
Gobe, Glenda C.
Venue: The International Journal of Biochemistry & Cell Biology
Publisher: Elsevier BV
Published: 2010-06
Volume: 42
Issue: 6
Pages: 813-827
ISSN: 1357-2725 (ISSN-L)
DOI: 10.1016/j.biocel.2009.11.013
OpenAlex: W1546185806
Cited by: 292
References: 172
Citations by year: 2026: 4 · 2025: 5 · 2024: 16 · 2023: 18 · 2022: 24 · 2021: 22 · 2020: 23 · 2019: 17 · 2018: 22 · 2017: 15 · 2016: 13 · 2015: 30 · 2014: 15 · 2013: 22 · 2012: 18
FWCI: 2.23
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: The International Journal of Biochemistry & Cell Biology (publishedVersion)
PubMed (publishedVersion)
Faculty of Health; Institute of Health and Biomedical Innovation
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords: androgen receptor, androgen signaling, nuclear translocation, transcriptional regulation, transcription factor crosstalk, androgen insensitivity syndrome, prostate cancer, androgen deprivation therapy, androgen receptor mutations
MeSH terms: Animals, Humans, Male, Polymorphism, Genetic, Prostatic Neoplasms, Receptors, Androgen, Gonadal Steroid Hormones, Androgen-Insensitivity Syndrome, Transcription Factors, Signal Transduction, Transcriptional Activation, Genetic Predisposition to Disease, Multiprotein Complexes

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Molecular cell biology of androgen receptor signalling

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