131983-72-7PPDBOQMNKNNODG-UHFFFAOYNA-NPPDBOQMNKNNODG-UHFFFAOYSA-N
Triticonazole5-[(4-Chlorophenyl)methylene]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol
DTXSID003265585509-19-9FQKUGOMFVDPBIZ-UHFFFAOYSA-NFQKUGOMFVDPBIZ-UHFFFAOYSA-N
FlusilazoleNuStar
DTXSID3024235133855-98-8ZMYFCFLJBGAQRS-UHFFFAOYNA-NZMYFCFLJBGAQRS-UHFFFAOYSA-N
EpoxiconazoleDTXSID104037267747-09-5TVLSRXXIMLFWEO-UHFFFAOYSA-NTVLSRXXIMLFWEO-UHFFFAOYSA-N
Prochloraz1H-Imidazole-1-carboxamide, N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]-
BTS 40542-7877
N-propil-N-[2-(2,4,6-triclorofenoxi)etil]-1H-imidazol-1-carboxamida
N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]-1H-imidazole-1-carboxamide
N-Propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl-1H-imidazole-1-carboxamide
N-Propyl-N-[2-(2,4,6-trichlorphenoxy)ethyl]-1H-imidazol-1-carboxamid
Plocloraz
Prelude
Sportak
Sportake
DTXSID402427060207-90-1STJLVHWMYQXCPB-UHFFFAOYNA-NSTJLVHWMYQXCPB-UHFFFAOYSA-N
Propiconazoleppz
1H-1,2,4-Triazole, 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-
(.+-.)-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl-methyl]-1H-1,2,4-triazole
(.+-.)-1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole
1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole
1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolane-2-yl]methyl]-1H-1,2,4-triazole
1-[[2-(2,4-Dichlorphenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazol
1-[[2-(2,4-diclorofenil)-4-propil-1,3-dioxolan-2-il]metil]-1H-1,2,4-triazol
Bamper 25EC
Banner Maxx
Cane Sett Treatment
Fertilome Liquid Systemic Fungicide
Microban PZ
Microban S 2140
Mycostat P
Proconazole
PROPICONAZOL
Tilt Premium
Wocosen Technical
Wocosin
Wocosin 50TK
DTXSID8024280107534-96-3PXMNMQRDXWABCY-UHFFFAOYNA-NPXMNMQRDXWABCY-UHFFFAOYSA-N
Tebuconazole1H-1,2,4-Triazole-1-ethanol, .alpha.-(2-(4-chlorophenyl)ethyl)-.alpha.
+-
1H-1,2,4-Triazole-1-ethanol, α-[2-(4-chlorophenyl)ethyl]-α-(1,1-dimethylethyl)-
(.+-.)-Tebuconazole
1-(4-Chlorophenyl)-4,4-dimethyl-3-(1,2,4-triazol-1-ylmethyl)pentan-3-ol
1H-1,2,4-Triazole-1-ethanol, α-[2-(4-chlorophenyl)ethyl]-α-(1,1-dimethylethyl)-, (.+-.)-
1H-1,2,4-Triazole-1-ethanol,α-[2-(4-chlorophenyl) ethyl]-α-(1,1-dimethylethyl)-, (.+-.)-
BAY-HWG 1608
ETHANOL, α-[2-(4-CHLOROPHENYL)ETHYL]-α- (1,1-DIMETHYLETHYL)-1H-1,2,4-TRIAZOLE
Ethyltrianol
Etiltrianol
Fenetrazole
Folicur
Microban S 2142
Microban TZ
Preventol A 8
TEBUCONAZOL
Tebuconazole Resp. HWG 1608
Terbutrazole
α-[2-(4-Chlorophenyl)-ethyl]-α-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol
α-[2-(4-chlorophenyl)ethyl]-α-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol
α-tert-Butyl-α-(p-chlorophenethyl)-1H-1,2,4-triazole-1-ethanol
DTXSID903211313311-84-7MKXKFYHWDHIYRV-UHFFFAOYSA-NMKXKFYHWDHIYRV-UHFFFAOYSA-N
FlutamidePropanamide, 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-
4-Nitro-3-(trifluoromethyl)isobutyranilide
4'-Nitro-3'-trifluoromethylisobutyranilide
Eulexin
Flucinom
Flutamid
flutamida
m-Propionotoluidide, α,α,α-trifluoro-2-methyl-4'-nitro-
N-(Isopropylcarbonyl)-4-nitro-3-trifluoromethylaniline
Niftholide
Niftolide
NSC 147834
NSC 215876
DTXSID7032004427-51-0UWFYSQMTEOIJJG-FDTZYFLXSA-NUWFYSQMTEOIJJG-FDTZYFLXSA-N
Cyproterone acetate3'H-Cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione, 17-(acetyloxy)-6-chloro-1,2-dihydro-, (1β,2β)-
1,2α-Methylene-6-chloro-17α-acetoxy-4,6-pregnadiene-3,20-dione
1,2α-Methylene-6-chloro-pregna-4,6-diene-3,20-dione 17α-acetate
1,2α-Methylene-6-chloro-Δ4,6-pregnadien-17α-ol-3,20-dione acetate
17-acetate de 6-chloro-1-β,2-β-dihydro-17-hydroxy-3'H-cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione
17-acetato de 6-cloro-1-β,2-β-dihidro-17-hidroxi-3'H-ciclopropa[1,2]pregna-1,4,6-trieno-3,20-diona
17α-Acetoxy-6-chloro-1α,2α-methylenepregna-4,6-diene-3,20-dione
3'H-Cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione
3'H-Cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione, 6-chloro-1β,2β-dihydro-17-hydroxy-, acetate
6-Chlor-1-β,2-β-dihydro-17-hydroxy-3'H-cyclopropa[1,2]pregna-1,4,6-trien-3,20-dion-17-acetat
6-Chloro-1,2α-methylene-17α-hydroxy-Δ6-progesterone acetate
6-Chloro-1,2α-methylene-6-dehydro-17α-hydroxyprogesterone acetate
6-Chloro-17-hydroxy-1α,2α-methylenepregna-4,6-diene-3,20-dione acetate
6-chloro-1-β,2-β-dihydro-17-hydroxy-3'H-cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione 17-acetate
Androcur
Cyprostat
Cyproterone 17-O-acetate
Cyproterone 17α-acetate
Cyproviron
NSC 81430
Pregna-4,6-diene-3,20-dione, 6-chloro-17-hydroxy-1α,2α-methylene-, acetate
DTXSID502036650471-44-8FSCWZHGZWWDELK-UHFFFAOYNA-NFSCWZHGZWWDELK-UHFFFAOYSA-N
Vinclozolin2,4-Oxazolidinedione, 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-
(.+-.)-Vinclozolin
BAS 352-04F
N-3,5-Dichlorophenyl-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione
N-3,5-Dichlorophenyl-5-methyl-5-vinyloxazolidine-2,4-dione
N-3,5-Dichlorphenyl-5-methyl-5-vinyl-1,3-oxazolidin-2,4-dion
N-3,5-diclorofenil-5-metil-5-vinil-1,3-oxazolidina-2,4-diona
Ornalin
Ranilan
Ronilan
Ronilan 50WP
DTXSID4022361Mercaptobenzole2016-11-29T18:42:262016-11-29T18:42:26Triticonazole2020-05-16T11:02:072020-05-16T11:09:42Flusilazole2020-05-16T11:15:342020-05-16T11:15:34Epoxiconazole2020-05-16T11:35:442020-05-16T11:35:44Prochloraz2016-11-29T18:42:222016-11-29T18:42:22Propiconazole2017-05-17T13:18:072017-05-17T13:18:07Tebuconazole2017-05-17T13:17:142017-05-17T13:17:14Flutamide2016-11-29T18:42:272016-11-29T18:42:27Cyproterone acetate2020-05-17T10:13:282020-05-17T10:13:28Vinclozolin2020-05-14T11:28:312020-05-14T11:28:31WCS_9606human10090mouse10116ratWikiUser_25human and other cells in cultureAntagonism, Androgen receptorAntagonism, Androgen receptorMolecular<p><u>The androgen receptor (AR) and its function</u></p>
<p>Development of the male reproductive system and secondary male characteristics is dependent on androgens (foremost testosterone (T) and dihydrotestosterone (DHT). T and the more biologically active DHT act by binding to the AR (<a href="#_ENREF_4" title="MacLean, 1993 #251">MacLean et al, 1993</a>; <a href="#_ENREF_5" title="MacLeod, 2010 #27">MacLeod et al, 2010</a>; <a href="#_ENREF_8" title="Schwartz, 2019 #252">Schwartz et al, 2019</a>), with human AR mutations and mouse knock-out models having established its pivotal role in masculinization and spermatogenesis (<a href="#_ENREF_9" title="Walters, 2010 #254">Walters et al, 2010</a>). The AR is a ligand-activated transcription factor belonging to the steroid hormone nuclear receptor family (<a href="#_ENREF_1" title="Davey, 2016 #250">Davey & Grossmann, 2016</a>). The AR has three domains; the N-terminal domain, the DNA-binding domain and the ligand-binding domain, with the latter being most evolutionary conserved. Apart from the essential role AR plays for male reproductive development and function (<a href="#_ENREF_9" title="Walters, 2010 #254">Walters et al, 2010</a>), the AR is also expressed in many other tissues and organs such as bone, muscles, ovaries and the immune system (<a href="#_ENREF_7" title="Rana, 2014 #253">Rana et al, 2014</a>). </p>
<p><u>AR antagonism as Key Event</u></p>
<p>The main function of the AR is to activate gene transcription in cells. Canonical signaling occurs by ligands (androgens) binding to AR in the cytoplasm which results in translocation to the cell nucleus, receptor dimerization and binding to specific regulatory DNA sequences (<a href="#_ENREF_2" title="Heemers, 2007 #255">Heemers & Tindall, 2007</a>). The gene targets regulated by AR activation depends on cell/tissue type and what stage of development activation occur, and is, for instance, dependent on available co-factors. Apart from the canonical signaling pathway, AR can also function through non-genomic modalities, for instance rapid change in cell function by ion transport changes (<a href="#_ENREF_3" title="Heinlein, 2002 #256">Heinlein & Chang, 2002</a>). However, with regard to this specific KE the canonical signaling pathway is what is referred to.</p>
<p>AR antagonism can be measured in vitro by transient or stable transactivation assays to evaluate nuclear receptor activation. There is already a validated assay for AR (ant)agonism adopted by the OECD, Test No. 458: <em>Stably Transfected Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity of Chemicals </em>(<a href="#_ENREF_13" title="OECD, 2016 #257">OECD, 2016</a>). The stably transfected AR-EcoScreen<sup>TM</sup> cells (<a href="#_ENREF_15" title="Satoh, 2004 #280">Satoh et al, 2004</a>) should be used for the assay and is freely available for the Japanese Collection of Research Bioresources (JCRB) Cell Bank under reference number JCRB1328.</p>
<p>Other assays include the AR-CALUX reporter gene assay that is derived from human U2-OS cells stably transfected with the human AR and an AR responsive reporter gene (<a href="#_ENREF_18" title="van der Burg, 2010 #261">van der Burg et al, 2010</a>), various transiently transfected reporter cell lines (<a href="#_ENREF_10" title="Körner, 2004 #282">Körner et al, 2004</a>), and more.</p>
<p><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">Recently developed AR dimerization assay may soon be included in TGs for its improved ability to measure potential stressor-mediated dimerization/activation </span></span><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">(</span></span><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif"><a href="#_ENREF_11" title="Lee, 2021 #288">Lee et al, 2021</a></span></span><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">)</span></span><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">.</span></span></p>
<p>Both the DNA-binding and ligand-binding domains of the AR are highly evolutionary conserved, whereas the transactivation domain show more divergence which may affect AR-mediated gene regulation across species (<a href="#_ENREF_1" title="Davey, 2016 #250">Davey & Grossmann, 2016</a>). Despite certain inter-species differences, AR function mediated through gene expression is highly conserved, with mutations studies from both humans and rodents showing strong correlation for AR-dependent development and function (<a href="#_ENREF_9" title="Walters, 2010 #254">Walters et al, 2010</a>).</p>
<p>This KE is applicable for both sexes, across developmental stages into adulthood, in numerous cells and tissues and across taxa</p>
CL:0000255eukaryotic cellHighMixedHighFoetalModerateEmbryoHighDuring development and at adulthoodHighHighHighHigh<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_1">Alapi EM, Fischer J (2006) Table of Selected Analogue Classes. In <em>Analogue-based Drug Discovery</em>, Fischer J, Ganellin CR (eds), p 515. Weinheim: Wiley-VCH Verlag GmbH & Co</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_2">Davey RA, Grossmann M (2016) Androgen Receptor Structure, Function and Biology: From Bench to Bedside. <em>Clin Biochem Rev</em> <strong>37:</strong> 3-15</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_3">Draskau MK, Boberg J, Taxvig C, Pedersen M, Frandsen HL, Christiansen S, Svingen T (2019) In vitro and in vivo endocrine disrupting effects of the azole fungicides triticonazole and flusilazole. <em>Environ Pollut</em> <strong>255:</strong> 113309</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_4">Foster PM, Harris MW (2005) Changes in androgen-mediated reproductive development in male rat offspring following exposure to a single oral dose of flutamide at different gestational ages. <em>Toxicol Sci</em> <strong>85:</strong> 1024-1032</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_5">Hass U, Scholze M, Christiansen S, Dalgaard M, Vinggaard AM, Axelstad M, Metzdorff SB, Kortenkamp A (2007) Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat. <em>Environ Health Perspect</em> <strong>115 Suppl. 1:</strong> 122-128</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_6">Heemers HV, Tindall DJ (2007) Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. <em>Endocr Rev</em> <strong>28:</strong> 778-808</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_7">Heinlein CA, Chang C (2002) The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. <em>Mol Endocrinol</em> <strong>16:</strong> 2181-2187</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_8">Kita DH, Meyer KB, Venturelli AC, Adams R, Machado DL, Morais RN, Swan SH, Gennings C, Martino-Andrade AJ (2016) Manipulation of pre and postnatal androgen environments and anogenital distance in rats. <em>Toxicology</em> <strong>368-369:</strong> 152-161</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_9">Kjærstad MB, Taxvig C, Nellemann C, Vinggaard AM, Andersen HR (2010) Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals. <em>Reprod Toxicol</em> <strong>30:</strong> 573-582</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_10">Körner W, Vinggaard AM, Térouanne B, Ma R, Wieloch C, Schlumpf M, Sultan C, Soto AM (2004) Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals. <em>Environ Health Perspect</em> <strong>112:</strong> 695-702</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_11">Lee SH, Hong KY, Seo H, Lee HS, Park Y (2021) Mechanistic insight into human androgen receptor-mediated endocrine-disrupting potentials by a stable bioluminescence resonance energy transfer-based dimerization assay. <em>Chem Biol Interact</em> <strong>349:</strong> 109655</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_12">MacLean HE, Chu S, Warne GL, Zajac JD (1993) Related individuals with different androgen receptor gene deletions. <em>J Clin Invest</em> <strong>91:</strong> 1123-1128</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_13">MacLeod DJ, Sharpe RM, Welsh M, Fisken M, Scott HM, Hutchison GR, Drake AJ, van den Driesche S (2010) Androgen action in the masculinization programming window and development of male reproductive organs. <em>Int J Androl</em> <strong>33:</strong> 279-287</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_14">OECD. (2016) Test No. 458: Stably Transfected Human Androgen Receptor Transcriptional Activation Assay for Detection of Androgenic Agonist and Antagonist Activity of Chemicals. <em>OECD Guidelines for the Testing of Chemicals, Section 4</em>, Paris.</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_15">Rana K, davey RA, Zajac JD (2014) Human androgen deficiency: insights gained from androgen receptor knockout mouse models. <em>Asian J Androl</em> <strong>16:</strong> 169-177</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_16">Satoh K, Ohyama K, Aoki N, Iida M, Nagai F (2004) Study on anti-androgenic effects of bisphenol a diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE) and their derivatives using cells stably transfected with human androgen receptor, AR-EcoScreen. <em>Food Chem Toxicol</em> <strong>42:</strong> 983-993</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_17">Schwartz CL, Christiansen S, Vinggaard AM, Axelstad M, Hass U, Svingen T (2019) Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders. <em>Arch Toxicol</em> <strong>93:</strong> 253-272</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_18">Sonneveld E, Jansen HJ, Riteco JA, Brouwer A, van der Burg B (2005) Development of androgen- and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays. <em>Toxicol Sci</em> <strong>83:</strong> 136-148</a></span></span></p>
<p> </p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_19">van der Burg B, Winter R, Man HY, Vangenechten C, Berckmans P, Weimer M, Witters H, van der Linden S (2010) Optimization and prevalidation of the in vitro AR CALUX method to test androgenic and antiandrogenic activity of compounds. <em>Reprod Toxicol</em> <strong>30:</strong> 18-24</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_20">Vinggaard AM, Niemelä J, Wedebye EB, Jensen GE (2008) Screening of 397 chemicals and development of a quantitative structure--activity relationship model for androgen receptor antagonism. <em>Chem Res Toxicol</em> <strong>21:</strong> 813-823</a></span></span></p>
<p><span style="font-size:11pt"><span style="font-family:"Calibri",sans-serif"><a name="_ENREF_21">Walters KA, Simanainen U, Handelsman DJ (2010) Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models. <em>Hum Reprod Update</em> <strong>16:</strong> 543-558</a></span></span></p>
2016-11-29T18:41:222022-06-15T06:17:59Decrease, androgen receptors (AR) activationDecrease, AR activationCellular<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif">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. <sup>12</sup></span></span></p>
<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif">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.<sup>3</sup></span></span></p>
<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif">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.<sup>4</sup></span></span></p>
<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif">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.<sup>5</sup></span></span></p>
<table>
<tbody>
<tr>
<td colspan="1" rowspan="1">
<p> </p>
</td>
<td colspan="1" rowspan="1">
<p><sup>1</sup> 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</p>
<p><sup>2 </sup>Gao W., Bohl C.E. and Dalton J.T. (2005) Chemistry and Structural Biology of Androgen Receptor. Chemical Reviews 105(9): 3352-3370<a href="https://www.google.com/url?q=https://doi.org/10.1021/cr020456u&sa=D&ust=1554891396627000">https://doi.org/10.1021/cr020456u</a> </p>
<p><sup>3</sup> 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.<a href="https://www.google.com/url?q=https://doi.org/10.1210/me.2011-1283&sa=D&ust=1554891396628000">https://doi.org/10.1210/me.2011-1283</a> </p>
<p><sup>4</sup> Hutson J.M. (1985) A biphasic model for the hormonal control of testicular descent. Lancet, 24;2(8452): 419-21<a href="https://www.google.com/url?q=http://dx.doi.org/10.1016/S0140-6736(85)92739-4&sa=D&ust=1554891396629000">http://dx.doi.org/10.1016/S0140-6736(85)92739-4</a> </p>
<p><sup>5</sup> 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 <a href="https://www.google.com/url?q=https://doi.org/0.1016/j.reprotox.2010.04.012&sa=D&ust=1554891396630000">https://doi.org/0.1016/j.reprotox.2010.04.012</a> </p>
</td>
</tr>
</tbody>
</table>
2019-04-10T05:04:182019-04-10T05:24:20decrease, transcription of genes by AR decrease, transcription of genes by AR Cellular2019-08-30T04:19:472019-08-30T04:19:47Malformation, cryptorchidism - maldescended testisMalformation, cryptorchidismOrgan<p style="text-align: justify;"><span style="font-family:times new roman,times,serif"><span style="font-size:14px">Undescended testis is a testicular disorder syndrome known as cryptorchidism. Testis migration is a major event in male fetus development, as it will directly affect his reproductive health.</span></span></p>
<p style="text-align: justify;"><span style="font-family:times new roman,times,serif"><span style="font-size:14px">Cryptorchidism can defined itself as the insertion of the testis in another position than the scrotum. Although the events leading to this pathology occurred during development, cryptorchidism can only be defined after birth though clinical examination as palpation.</span></span></p>
<p style="text-align: justify;"><span style="font-family:times new roman,times,serif"><span style="font-size:14px">Cryptorchidism can be either uni- or bilateral and has been reported to increase in incidence over the decades (Denmark, UK, India…). The maldescended testis will experiment heat stress (37 against 33C outside the body) interfering with testicular physiology and development of germ cells into spermatogonia. Germ cells maturation failure will induce a non-reversible reduction in fertility power of the individual. Cryptorchidism is an established risk factor for infertility and is known to increase the incidence of testicular germ cell tumors (TGCT) <sup>123</sup></span></span></p>
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<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif">Remark: </span></span></p>
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<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif">Cryptorchidism is the first AO of a larger list including raise in testicular cancer and germ cell tumor incidence, as well as reduced fertility due to impairment in germ cells maturation.</span></span></p>
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<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif">Cryptorchidism is a birth defect that can be highlighted by a clinical examination. The aim of this palpation is to locate the gonad and determine its lowest position without causing painful traction on the spermatic cord. <sup>4</sup></span></span></p>
<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif"><sup>1</sup> Hutson J.M., Li R., Southwell B.R., Newgreen D., and Cousinery M. (2015) Regulation of testicular descent. Pediatric Surgery International, 31(4): 317-325. <a href="https://www.google.com/url?q=https://doi.org/10.1007/s00383-015-3673-4&sa=D&ust=1554891396648000">https://doi.org/10.1007/s00383-015-3673-4</a> </span></span></p>
<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif"><sup>2</sup> Boisen K.A., Kaleva M., Main K.M., Virtanen H.E., Haavisto A.M., Schmidt I.M., Chellakooty M., Damgaard I.N., Mau C., Reunanen M., Skakkebaek N.E. and Toppari J. (2004) Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet, 17;363(9417):1264-9 <a href="https://www.google.com/url?q=https://doi.org/10.1016/S0140-6736(04)15998-9&sa=D&ust=1554891396649000">https://doi.org/10.1016/S0140-6736(04)15998-9</a> </span></span></p>
<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif"><sup>3</sup> Acerini C.L., Miles H.L., Dunger D.B., Ong K.K. and Hughes I.A. (2009) The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort. Archives of disease in childhood, 94(11):868-72 https://doi.org10.1136/adc.2008.150219 </span></span></p>
<p style="text-align: justify;"><span style="font-size:14px"><span style="font-family:times new roman,times,serif"><sup>4</sup> Hutson J.M., et al. (2015) Cryptorchidism and Hypospadias. Endotext<a href="https://www.google.com/url?q=https://www.ncbi.nlm.nih.gov/books/NBK279106/&sa=D&ust=1554891396651000">https://www.ncbi.nlm.nih.gov/books/NBK279106/</a> </span></span></p>
2019-04-10T05:06:572019-04-10T05:27:42Testicular CancerTesticular CancerOrgan2021-02-12T12:17:362021-02-12T12:17:36Androgen receptor antagonism leading to testicular cancer Androgen receptor antagonism and testicular cancerUnder development: Not open for comment. Do not cite<p>A large number of drugs and chemicals have been shown to antagonise the AR using various AR reporter gene assays. The AR is specifically targeted in AR-sensitive cancers, for example the use of the anti-androgenic drug flutamide in treating prostate cancer (<a href="#_ENREF_1" title="Alapi, 2006 #262">Alapi & Fischer, 2006</a>). Flutamide has also been used in several rodent in vivo studies showing anti-androgenic effects (feminization of male offspring) evident by e.g. short anogenital distance (AGD) in males (<a href="#_ENREF_4" title="Foster, 2005 #53">Foster & Harris, 2005</a>; <a href="#_ENREF_5" title="Hass, 2007 #76">Hass et al, 2007</a>; <a href="#_ENREF_8" title="Kita, 2016 #34">Kita et al, 2016</a>). QSAR models can predict AR antagonism for a wide range of chemicals, many of which have shown in vitro antagonistic potential (<a href="#_ENREF_17" title="Vinggaard, 2008 #263">Vinggaard et al, 2008</a>).</p>
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