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Event: 1614
Key Event Title
Decrease, androgen receptors (AR) activation
Short name
Biological Context
Cell term
Organ term
Key Event Components
Process | Object | Action |
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Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
Cyp17A1 inhibition leads to undescended testes in mammals | KeyEvent | Bérénice COLLET (send email) | Open for citation & comment | |
5α-reductase inhibition leading to short AGD | KeyEvent | Terje Svingen (send email) | Under development: Not open for comment. Do not cite | Under Development |
AR antagonism leading to short AGD | KeyEvent | Terje Svingen (send email) | Under development: Not open for comment. Do not cite | Under Development |
Decreased testosterone synthesis leading to short AGD | KeyEvent | Terje Svingen (send email) | Under development: Not open for comment. Do not cite | Under Development |
AR antagonism leading to NR | KeyEvent | Terje Svingen (send email) | Under development: Not open for comment. Do not cite |
Stressors
Taxonomic Applicability
Life Stages
Sex Applicability
Key Event Description
Androgen receptor activation is regulated by the binding of androgens. AR activity can be decreased by either a lack of steroidal ligands (testosterone, DHT) or the presence of antagonist compounds. 12
How It Is Measured or Detected
Significance of AR signaling in fetal development can be studied through a conditional deletion of the androgen receptor using a Cre/loxP approach. The recommended animal model for reproductive study is the mouse.3
Also, epidemiological case-studies following mouse or humans expressing a complete androgen insensitivity allow to directly assess the effects of a lack of AR activation on the development.4
Enzyme immunoassay (ELISA) kits for in vitro quantitative measurement of AR activity are available. Androgen receptors activity can be measured using bioassay such as the (Anti-)Androgen Receptor CALUX reporter gene assay.5
Domain of Applicability
References
1 Davey R.A and Grossmann M. (2016) Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clinical Biochemist Reviews, 37(1): 3-15. PCM4810760 2 Gao W., Bohl C.E. and Dalton J.T. (2005) Chemistry and Structural Biology of Androgen Receptor. Chemical Reviews 105(9): 3352-3370https://doi.org/10.1021/cr020456u 3 Kaftanovskaya E.M., Huang Z., Barbara A.M., De Gendt K., Verhoeven G., Ivan P. Gorlov, and Agoulnik A.I. (2012) Cryptorchidism in Mice with an Androgen Receptor Ablation in Gubernaculum Testis. Molecular Endocrinology, 26(4): 598-607.https://doi.org/10.1210/me.2011-1283 4 Hutson J.M. (1985) A biphasic model for the hormonal control of testicular descent. Lancet, 24;2(8452): 419-21http://dx.doi.org/10.1016/S0140-6736(85)92739-4 5 van der Burg B., Winter R., Man HY., Vangenechten C., Berckmans P., Weimer M., Witters M. and van der Linden S. (2010) Optimization and prevalidation of the in vitro AR CALUX method to test androgenic and antiandrogenic activity of compounds. Reproductive Toxicology, 30(1):18-24 https://doi.org/0.1016/j.reprotox.2010.04.012 |