Androgen receptor functions in male and female physiology

Μatsumoto, Takahiro; Shiina, Hiroko; Kawano, Hirotaka; Satō, Takashi; Kato, Shigeaki

doi:10.1016/j.jsbmb.2008.03.023

Cited by 86 publications

(63 citation statements)

References 46 publications

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“…Androgens play an important role in prostate gland development, physiology and tumor proliferation. The effects of androgens are mediated by the androgen receptor (AR), a ligandactivated transcription factor of the nuclear receptor superfamily [13]. Androgens bind to the ligand-binding domain of the AR and cause a conformational change that enables the AR to dimerize, bind to the response elements of its target genes, and recruit the coactivators required to activate gene expression.…”

Section: Introductionmentioning

confidence: 99%

Androgens down-regulate myosin light chain kinase in human prostate cancer cells

Léveillé

Fournier

Labrie

2009

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Introductionmentioning

confidence: 99%

Androgens down-regulate myosin light chain kinase in human prostate cancer cells

Léveillé

Fournier

Labrie

2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…AR mediates various biological effects such as the development of male reproductive tissues, sexual development, and spermatogenesis. [1][2][3][4] Since androgen declining with age contributes to age-related bone and muscle loss and increase in fat mass, 5) the anabolic effect of androgen is attractive for the maintenance of health. Furthermore, it is known that AR is involved in androgen-dependent prostate cancer growth.…”

mentioning

confidence: 99%

(17.ALPHA.,20E)-17,20-[(1-Methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic Acid Methyl Ester (YK11) Is a Partial Agonist of the Androgen Receptor

Kanno

Hikosaka

Zhang

et al. 2011

Biological & Pharmaceutical Bulletin

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The androgen receptor (AR) is a member of the nuclear receptor (NR) superfamily of ligand-dependent transactivation factors. Androgens such as testosterone and 5-a-dihydrotestosterone (DHT) act as agonists of AR. AR mediates various biological effects such as the development of male reproductive tissues, sexual development, and spermatogenesis. [1][2][3][4] Since androgen declining with age contributes to age-related bone and muscle loss and increase in fat mass, 5) the anabolic effect of androgen is attractive for the maintenance of health. Furthermore, it is known that AR is involved in androgen-dependent prostate cancer growth. Thus, antagonists of AR (flutamide, bicalutamide, and nilutamide) are used in anti-androgen therapy for prostate cancer. 8,9) AR mediates the expression of androgen-regulated genes, as represented by prostate specific antigen (PSA) [10][11][12] and FK506-binding protein 51 (FKBP51). [13][14][15] In the absence of a ligand, AR is localized in the cytoplasm, where it forms complexes with chaperones. Upon ligand binding, AR translocates into the nucleus. Following nuclear translocation, AR binds to androgen responsive elements (ARE) in the promoter regions of its target genes as a homodimer. Generally, the transcriptional activity of nuclear receptors is modulated by their interaction with cofactors such as coactivators and corepressors. [16][17][18][19] The type of ligand that binds to the receptor determines which type of cofactor is chosen. In the case of agonists, AR interacts with coactivators dominantly over corepressors, and vice versa in the case of antagonists.Unlike other nuclear receptors, AR AF2 demonstrates weak transcriptional activity. However, ligand-dependent interaction between NTD and LBD/AF2 (which is termed as the N/C interaction) endows AR with synergistic transactivation potential. [20][21][22][23] Thus, the N/C interaction is important for the ligand-dependent transactivation potential of AR.Synthetic AR ligands are useful for treatment of prostate cancer and age-related diseases such as osteopenia and sarcopenia. Previously, we prepared novel synthetic steroids.24) In our preliminary screening for novel AR ligands, a steroid compound, (17a,20E)-17,20-[(1-methoxyethylidene) bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11), behaved apparently as a partial agonist of AR in an ARE-luciferase reporter assay (unpublished data). We were interested in this partial agonistic nature of YK11. In this report, we will show that YK11 blocks the N/C-interaction required for the full-agonistic function of wild-type AR, inducing selective AR-target genes owing to the constitutive transactivation potential of AF-1 subdomain in endogenous AR-expressing MDA-MB 453 cells. MATERIALS AND METHODS ChemicalsThe compounds tested in our preliminary screening for novel AR ligands were prepared by previously

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“…The gene expression levels of AR reflect the reproductive function of the rat (18)(19)(20). Therefore, the localization and quantitative analysis of AR was performed using immunological assays.…”

Section: Localization and Quantitative Expression Of Androgen Receptormentioning

confidence: 99%

The effect of microgravity on tissue structure and function of rat testis

Ding

Tang

Zou

et al. 2011

Braz J Med Biol Res

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Androgen receptor functions in male and female physiology

Cited by 86 publications

References 46 publications

Androgens down-regulate myosin light chain kinase in human prostate cancer cells

Androgens down-regulate myosin light chain kinase in human prostate cancer cells

(17.ALPHA.,20E)-17,20-[(1-Methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic Acid Methyl Ester (YK11) Is a Partial Agonist of the Androgen Receptor

The effect of microgravity on tissue structure and function of rat testis

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