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

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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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Background
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Boroujeni, P. B., Firouzi, V., Moradi, S. Z., Mokhtari, P., Dehghankhalili, F., Mollaahmadi, F., Gourabi, H., Gilani, M. A. S., Sabbaghian, M., & Meybodi, A. M. (2018) · Andrologia · doi:10.1111/and.13121 · Cited by 12
Histoprotective Effect of Essential Oil from Citrus aurantifolia in Testosterone-Induced Benign Prostatic Hyperplasia Rat
Acheampong, D. O., Kyei-Barffour, I., Boye, A., et al. (2019) · Advances in Urology · doi:10.1155/2019/3031609 · Cited by 12
Discovery of Novel Anti‐Resistance AR Antagonists Guided by Funnel Metadynamics Simulation
Chen, H., Zhou, Y., Wang, X., Chai, X., Wang, Z., Wang, E., Xu, L., Hou, T., Li, D., & Duan, M. (2024) · Advanced Science · doi:10.1002/advs.202309261 · Cited by 13
Mild Androgen Insensitivity Syndrome: The Current Landscape
Batista, R. L., Craveiro, F. L., Ramos, R. M., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.05.009 · Cited by 11
Chlorpropham, a carbamate ester herbicide, has an endocrine-disrupting potential by inhibiting the homodimerization of human androgen receptor
Jeong, D.-H., Jung, D., Jang, C.-H., et al. (2023) · Environmental Pollution · doi:10.1016/j.envpol.2023.121437 · Cited by 11
Role of insulin and testosterone in prostatic growth: Who is doing what?
Vikram, A., & Jena, G. (2010) · Medical Hypotheses · doi:10.1016/j.mehy.2010.11.024 · Cited by 11
Detection of ADP-Ribosylation of the Androgen Receptor Using the Recombinant Macrodomain AF1521 from Archaeoglobus fulgidus
Kamata, T., Yang, C., Jividen, K., Spencer, A., Dworak, N. M., Oostdyk, L. T., & Paschal, B. M. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9195-2_9 · Cited by 10
Halowax 1051 affects steroidogenesis by down-regulation of aryl hydrocarbon and estrogen receptors and up-regulation of androgen receptor in porcine ovarian follicles
Barć, J., & Gregoraszczuk, E. Ł. (2015) · Chemosphere · doi:10.1016/j.chemosphere.2015.09.026 · Cited by 11
“Some studies have suggested that, in granulosa cells, the AR uses AHR as a cofactor, which play a major role in AR signal transduction and function (Bennett et al., 2010; Wu et al., 2013).”
Background
Expression of the androgen receptor in the testes and the concentrations of gonadotropins and sex steroid hormones in male turkeys (Meleagris gallopavo) during growth and development
Kieżun, J., Leska, A., Kamińska, B., Jankowski, J., & Dusza, L. (2014) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2014.07.012 · Cited by 12
“Testosterone (T), the major androgenic steroid, modulates the expression of various behaviours linked to reproduction, territoriality, aggression and the development of secondary sexual characteristics (Bennett et al., 2010; Garamszegi et al., 2004; Maney et al., 2009; Matsumoto et al., 2008).”
Background
The role of the androgen receptor as a driver and mitigator of cellular stress
Doultsinos, D., & Mills, I. G. (2020) · Journal of Molecular Endocrinology · doi:10.1530/jme-20-0057 · Cited by 10
“It is tethered to the cytoplasm by filamin A, and binding of androgens such as DHT induces conformational changes in the AR to form an activation function binding surface (Bennett et al. 2010).”
Differential distribution of steroid hormone signaling networks in the human choroid-retinal pigment epithelial complex
Galindez, S. M., Keightley, A., & Koulen, P. (2022) · BMC Ophthalmology · doi:10.1186/s12886-022-02585-7 · Cited by 9
“AR typically forms a homodimer and is then translocated across the nuclear membrane where it binds to androgen response elements (AREs) and induces the transcription of androgen-dependent genes [9, 10].”
Background
Neonatal Lung Disease: Mechanisms Driving Sex Differences
Lingappan, K., Hayward-Piatkovskyi, B., & Gleghorn, J. P. (2021) · Physiology in health and disease · doi:10.1007/978-3-030-63549-7_5 · Cited by 11
Androgen receptor functions as a negative transcriptional regulator of DEPTOR, mTOR inhibitor
Kanno, Y., Zhao, S., Yamashita, N., et al. (2015) · The Journal of Toxicological Sciences · doi:10.2131/jts.40.753 · Cited by 10
“AR also plays a central role in prostate cancer growth and development (Heinlein and Chang, 2004; Dehm and Tindall, 2007; Bennett et al., 2010).”
Background
Design, synthesis, and evaluation of the antiproliferative activity of hydantoin-derived antiandrogen-genistein conjugates
George, A. B., Raji, I. O., Cinar, B., Küçük, Ö., & Oyelere, A. K. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.01.009 · Cited by 10
Sex Steroids and Their Influence in Lung Diseases Across the Lifespan
Borkar, N. A., & Sathish, V. (2021) · Physiology in health and disease · doi:10.1007/978-3-030-63549-7_3 · Cited by 10
Regulatory mechanism of androgen receptor on NCAPD3 gene expression in prostate cancer
Yin, Y., Liu, Q., Shao, Y., He, X., Zhu, Q., Lu, S., & Liu, P. (2021) · The Prostate · doi:10.1002/pros.24245 · Cited by 10
“receptor (AR), which induces a gene expression program promoting PCa cell proliferation and survival.(2,3) By binding to androgen, cytoplasmic AR translocates into the nucleus, where AR directly binds to androgen receptor binding sites (ARBS) in the transcription‐regulatory regions of various target genes and then reg…”
Emerging proteins involved in castration‑resistant prostate cancer via the AR‑dependent and AR‑independent pathways (Review)
Feng, K., Liu, C., Wang, W., Kong, P., Tao, Z., & Liu, W. (2023) · International Journal of Oncology · doi:10.3892/ijo.2023.5575 · Cited by 10
Dual effects of constitutively active androgen receptor and full-length androgen receptor for N-cadherin regulation in prostate cancer
Cottard, F., Madi-Berthélémy, P. O., Erdmann, É., Schaff-Wendling, F., Keime, C., Ye, T., Kurtz, J., & Céraline, J. (2017) · Oncotarget · doi:10.18632/oncotarget.18270 · Cited by 10
“Since the ligand-binding domain (LBD) is an important platform for the interaction of cofactors, the loss of this region in AR variants could partly explain the distinct transcriptional programs in the presence of AR-FL or AR variants [40].”
Background
In silico and functional studies reveal novel loss-of-function variants of SRD5A2, but no variants explaining excess 5α-reductase activity
Katharopoulos, E., Sauter, K., Pandey, A. V., & Flück, C. E. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.01.017 · Cited by 9
Evidence for enhanced androgen action in the prefrontal cortex of people with bipolar disorder but not schizophrenia or major depressive disorder
Owens, S. J., Purves-Tyson, T. D., Webster, M. J., & Weickert, C. S. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.112503 · Cited by 9
Modulation of inflammatory and hormonal parameters in response to testosterone therapy: Effects on the ventral prostate of adult rats
Mendes, L. D. O., Castilho, A. C. S., Pinho, C. F., Gonçalvez, B. F., Razza, E. M., Chuffa, L. G. D. A., Anselmo-Franci, J. A., Scarano, W. R., & Martinez, F. E. (2018) · Cell Biology International · doi:10.1002/cbin.10990 · Cited by 8
“The androgen signaling pathway involves the expression of several proteins that regulate prostatic growth (Bennett et al., 2010), which might explain the higher proliferation index observed after TT.”
Background
Testosterone-loaded GM1 micelles targeted to the intracellular androgen receptor for the specific induction of genomic androgen signaling
Peinetti, N., Cuello Rubio, M. M., Sosa, L. D. V., Scalerandi, M. V., Alasino, R. V., Peyret, V., Nicola, J. P., Beltramo, D. M., Quintar, A. A., & Maldonado, C. A. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119985 · Cited by 7
Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy
Celestra, D., Nguyen, N. N. L., Laberthonnìère, C., Pang, K. C., Saffery, R., Davey, R. A., Mhlanga, M. M., Cheung, A. S., & Novakovic, B. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1501959 · Cited by 9
Deficiency in Androgen Receptor Aggravates Traumatic Brain Injury-Induced Pathophysiology and Motor Deficits in Mice
Chen, Y., Chen, Y., Hwang, L.-L., Yang, L., & Lu, D. (2021) · Molecules · doi:10.3390/molecules26206250 · Cited by 8
“Aberrant androgen receptors (ARs) activity, which usually occurs with mutations or binding partner misregulation, can be clinically recognized as androgen insensitivity syndrome and prostate cancer [52].”
Background
Androgen effect on connexin expression in the mammalian female reproductive system: a systematic review
Kamal, D. A. M., Ibrahim, S. F., & Mokhtar, M. H. (2019) · Bosnian Journal of Basic Medical Sciences · doi:10.17305/bjbms.2019.4501 · Cited by 7
“The AR also utilizes the non-genomic pathway to exert the effects of androgen, through the modulation of cytoplasmic or cell membrane-bound regulatory proteins [3].”
Background
Genetic Variation in the Androgen Receptor Modifies the Association Between Testosterone and Vitality in Middle-Aged Men
Panizzon, M. S., Bree, K. K., Hsieh, T., Hauger, R. L., Xian, H., Jacobson, K. C., Lyons, M. J., & Franz, C. E. (2020) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2020.08.016 · Cited by 6
“Testosterone primarily influences peripheral tissues and the central nervous system by binding to and activating the AR [21, 22]; however, the interplay of testosterone with the AR is known to differ as a function of a trinucleotide (CAG) repeat located on exon 1 of the AR gene [23, 24].”
Background
Androgen receptor gene deficiency results in the reduction of steroidogenic potential in porcine luteal cells
Bharati, J., Kumar, S., kumar, S., V, Mohan, N. H., Islam, R., Pegu, S. R., Banik, S., Das, B. C., Borah, S. R., & Sarkar, M. (2022) · Animal Biotechnology · doi:10.1080/10495398.2022.2079517 · Cited by 7
“1,42 In females AR mediated auto-crine and/or paracrine role for androgens has been ascribed in primate ovary, 43 however the role of AR mediated actions in luteal physiology remains largely unclear.”
Involvement of GLCCI1 in mouse spermatogenesis
Takada, M., Fukuhara, D., Takiura, T., et al. (2022) · The FASEB Journal · doi:10.1096/fj.202101667rr · Cited by 6
A novel L-shaped ortho-quinone analog suppresses glioblastoma progression by targeting acceleration of AR degradation and regulating PI3K/AKT pathway
Zhang, T., Pan, W., Tan, X., Yu, J., Cheng, S., Wei, S., Fan, K., Wang, L., Luo, H., & Hu, X. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116398 · Cited by 5
Testicular Feminization or Androgen Insensitivity Syndrome (AIS) in Iran: a Retrospective Analysis of 30-Year Data.
Farhud, D. D., Yeganeh, M. Z., Sadighi, H., et al. (2016) · PubMed · Cited by 6
Cimetidine‐induced androgenic failure causes cell death and changes in actin, EGF and V‐ATPase immunoexpression in rat submandibular glands
Manzato, M., de Santi, F., da Silva, A. A. S., et al. (2021) · Journal of Anatomy · doi:10.1111/joa.13408 · Cited by 6
“Interestingly, both actin cytoskeleton integrity (Stournaras et al., 2014) and PKA activation (Bennett et al., 2010) are regulated by non- genomic AR action.”
Background
Androgen regulated protein and pyruvate dehydrogenase kinase 4 in severe erectile dysfunction: A gene expression analysis, and computational study of protein structure
Kazemi, E., Zargooshi, J., Dehpahni, M. F., Motlagh, H.-R. M., Kaboudi, M., Kahrizi, D., Khazaie, H., Mahaki, B., Mohammadian, Y., & Yazdani, L. (2021) · Cellular and Molecular Biology · doi:10.14715/cmb/2021.67.2.13 · Cited by 6
The intricate interplay between circadian rhythm, androgen signaling, hormone therapy, and cellular senescence in prostate cancer
Horestani, M. H., & Baniahmad, A. (2025) · Cancer and Metastasis Reviews · doi:10.1007/s10555-025-10302-1 · Cited by 5
“The AR undergoes, e.g., serine phosphorylation at several sites (Ser81, Ser93, Ser641, Ser213, Ser506, and Ser650), which enhances its stability and transcriptional activity [70, 71].”
Androgen Receptor
Modi, P. K., Faiena, I., & Kim, I. Y. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800077-9.00003-7 · Cited by 5
Evolution of androgen receptors contributes to species variation in androgenic regulation of communication signals in electric fishes
Proffitt, M. R., Liu, X., Ortlund, E. A., & Smith, G. T. (2023) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2023.112068 · Cited by 5
Factors Regulating Neurogenesis in the Adult Dentate Gyrus
Zhang, L., & Zhang, X. (2018) · InTech eBooks · doi:10.5772/intechopen.75631 · Cited by 7
HepaCAM inhibits cell proliferation and invasion in prostate cancer by suppressing nuclear translocation of the androgen receptor via its cytoplasmic domain
Deng, Q., Luo, L., Quan, Z., Liu, N., Du, Z., Sun, W., Luo, C., & Wu, X. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.9841 · Cited by 5
“Nuclear translocation of AR is one of the most important steps in AR signalling transduction (25).”
Could androgens maintain specific domains of mental health in aging men by preserving hippocampal neurogenesis?
Ransome, M. I. (2012) · Europe PMC (PubMed Central) · doi:10.3969/j.issn.1673-5374.2012.028.009 · Cited by 5
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Mechanical Load, Sex Hormones, and Bone Modeling
Windahl, S. H., & Lerner, U. H. (2021) · Wiley eBooks · doi:10.1002/9781119608912.ch7 · Cited by 7
Sex differences in immune cells: mechanistic perspectives and clinical correlates in physiology and disease
Liao, X., Wu, D., Gao, J., Xie, F., Li, Z., Wang, M., Wang, K., Gao, Y., Li, Q., & Gao, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1650527 · Cited by 4
More Than Androgens: Hormonal and Paracrine Signaling in Prostate Development and Homeostasis
Felgueiras, J., Camilo, V., Fardilha, M., & Jerónimo, C. (2020) · Springer eBooks · doi:10.1007/978-3-030-44436-5_7 · Cited by 6
The triazole fungicide metconazole inhibits the homodimerization of human androgen receptors to suppress androgen-induced transcriptional activation
Jung, D.-W., Jeong, D.-H., Kim, U.-J., et al. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110489 · Cited by 4

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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › 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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