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Gene Review

AR  -  androgen receptor

Canis lupus familiaris

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Disease relevance of AR

  • In the prostate, AR was presented in both the epithelial and stromal cells and the AR mRNA level was higher in hyperplasia than in normal prostate tissues (P<0.05) [1].
  • Our objective was to determine whether the selective beta blocker, metoprolol, or the nonselective intrinsic sympathomimetic activity (ISA)-blocker pindolol, reduce infarct size as a function of an area at risk (AR) in a permanent infarction model in dogs and which blocker is preferable in regards to myocardial function [2].
  • Myocardial infarct size (IS) was evaluated using the tetrazolium staining technique and expressed as a percent of area at risk (AR) [3].
  • The grade of differentiation of hepatoid carcinomas did not affect AR expression [4].
  • CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity [5].

High impact information on AR

  • AN/AR was smaller in preconditioned versus control dogs that received no treatment (6 +/- 2% versus 19 +/- 3%, P < .01), H-7 (2 +/- 2% versus 14 +/- 5%, P < .02), or polymyxin B (10 +/- 3% versus 29 +/- 5%, P < .01) during the preconditioning or control period [6].
  • In PH beagles, ET-1 infusion increased SAP, which was attenuated by FR139317 (an endothelin type [ET] A receptor antagonist), and produced a dose-dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist) [7].
  • Stimulation of the renin-angiotensin system by endothelin subtype A receptor blockade in conscious dogs [8].
  • Deferoxamine administered at the time of reperfusion, however, had no significant effect on infarct size (AN/AR = 54.3 +/- 8.7%, p = NS vs. controls) [9].
  • Compound 6 produces potent anorectic activity via the CCK-A receptor system [5].

Chemical compound and disease context of AR


Biological context of AR

  • To further characterize AR function in a model species of relevance to bone and pharmaceutical research, we cloned a partial canine AR from a canine kidney cDNA library and then cloned the remaining 5' segment by PCR from canine ventral prostate cDNA [12].
  • In addition, the inactivation of AR binding activity by radiation was attributed to a loss of binding sites, with no significant change in the Kd [13].
  • The present findings suggest that there is a basal expression of AR in the canine uterus throughout the estrus cycle that may not be influenced by sex steroid hormones [14].
  • During pregnancy and in the postpartum period nuclear staining for AR was nearly absent [14].
  • There was no evident effect of the stage of ovarian cycle on uterine AR mRNA levels [15].

Anatomical context of AR

  • Immunohistochemistry using an antibody directed to the C-terminal 19 amino acids of the human AR showed strong staining of the secretory epithelial cells in canine ventral prostate [12].
  • Northern analysis of poly-A+ RNA from ventral prostate revealed three very low abundance transcripts of approximately 9 kb and RT-PCR analysis showed relatively high expression of AR in canine ventral prostate, testis, and kidney, with lower levels detectable in spleen, skeletal muscle, heart, and liver [12].
  • Increased number of neurons expressing androgen receptor in the basolateral amygdala of pathologically aggressive dogs [16].
  • To find out whether androgens can have a direct impact on the canine uterus, androgen receptors (AR) were identified immunohistochemically in uterine tissue [14].
  • Nuclear staining for AR was observed in cells of the surface epithelium, glandular ducts, basal glands and stroma of the endometrium, and in myometrial smooth muscle cells [14].

Associations of AR with chemical compounds

  • Androgen may direct the proliferation, differentiation and regression of stromal cells by regulating the expression of TGFbgr, bFGF, AR and smooth muscle cell specific proteins [1].
  • Binding of DHT also resulted in the stimulation of an androgen responsive-luciferase reporter following cotransfection with the canine AR into 293 cells [12].
  • This indicates that genomic androgen actions, which are mediated through the AR are of minor importance in the testosterone modulation of canine aggression within the BNG [16].
  • To maximize the binding activity, molybdate and dithiothreitol were included during AR extraction [13].
  • The area of necrosis (AN) was identified histologically with triphenyl tetrazolium chloride and calculated as percent of AR [17].

Other interactions of AR


Analytical, diagnostic and therapeutic context of AR

  • Within the early phase of castration (<d7), the expression of AR was increased rapidly [1].
  • To our knowledge, this is the first report relative to AR immunohistochemistry in canine mammary cancer and to estrogens or androgens in serum of dogs with benign or malignant mammary tumors [19].
  • Molecular cloning and functional characterization of the canine androgen receptor [12].
  • The IS/AR ratio for the control group was 29.8 +/- 4.4% (n = 17), which was substantially greater (p less than 0.001) than that of the preconditioned groups: P1, 3.9 +/- 1.3% (n = 14); P6, 0.4 +/- 0.3% (n = 5); and P12, 2.9 +/- 2.8% (n = 5) [20].
  • Collateral blood flow was assessed with radioactive microspheres; area at risk (AR) was delineated by injection of blue dye; and the area of necrosis (AN) was measured by tetrazolium staining [6].


  1. Androgen and prostatic stroma. Niu, Y.J., Ma, T.X., Zhang, J., Xu, Y., Han, R.F., Sun, G. Asian J. Androl. (2003) [Pubmed]
  2. Failure of pindolol and metoprolol to reduce the size of non-reperfused infarcts in dogs using area at risk techniques. Lange, R., Nieminen, M.S., Kloner, R.A. Cardiovasc. Res. (1984) [Pubmed]
  3. Protection of ischemic/reperfused canine myocardium by CL18/6, a monoclonal antibody to adhesion molecule ICAM-1. Hartman, J.C., Anderson, D.C., Wiltse, A.L., Lane, C.L., Rosenbloom, C.L., Manning, A.M., Humphrey, W.R., Wall, T.M., Shebuski, R.J. Cardiovasc. Res. (1995) [Pubmed]
  4. Androgen receptor expression in normal, hyperplastic and neoplastic hepatoid glands in the dog. Pisani, G., Millanta, F., Lorenzi, D., Vannozzi, I., Poli, A. Res. Vet. Sci. (2006) [Pubmed]
  5. Synthesis and biological evaluation of potent, selective, hexapeptide CCK-A agonist anorectic agents. Pierson, M.E., Comstock, J.M., Simmons, R.D., Kaiser, F., Julien, R., Zongrone, J., Rosamond, J.D. J. Med. Chem. (1997) [Pubmed]
  6. Does ischemic preconditioning trigger translocation of protein kinase C in the canine model? Przyklenk, K., Sussman, M.A., Simkhovich, B.Z., Kloner, R.A. Circulation (1995) [Pubmed]
  7. Role of endothelin-1 in beagles with dehydromonocrotaline-induced pulmonary hypertension. Okada, M., Yamashita, C., Okada, M., Okada, K. Circulation (1995) [Pubmed]
  8. Stimulation of the renin-angiotensin system by endothelin subtype A receptor blockade in conscious dogs. Berthold, H., Münter, K., Just, A., Kirchheim, H.R., Ehmke, H. Hypertension (1999) [Pubmed]
  9. Early treatment with deferoxamine limits myocardial ischemic/reperfusion injury. Reddy, B.R., Kloner, R.A., Przyklenk, K. Free Radic. Biol. Med. (1989) [Pubmed]
  10. Androgen receptors in the pelvic diaphragm muscles of dogs with and without perineal hernia. Mann, F.A., Nonneman, D.J., Pope, E.R., Boothe, H.W., Welshons, W.V., Ganjam, V.K. Am. J. Vet. Res. (1995) [Pubmed]
  11. Androgen receptor content of nafoxidine treated experimentally induced canine prostatic hyperplasia. Trachtenberg, J. Clinical and investigative medicine. Médecine clinique et experimentale. (1985) [Pubmed]
  12. Molecular cloning and functional characterization of the canine androgen receptor. Lu, B., Smock, S.L., Castleberry, T.A., Owen, T.A. Mol. Cell. Biochem. (2001) [Pubmed]
  13. Radiation-inactivation size of transformed and non-transformed androgen receptors. Turcotte, G., Beauregard, G., Potier, M., Chevalier, S. Biochem. J. (1991) [Pubmed]
  14. Immunohistochemical detection of androgen receptors in the canine uterus throughout the estrus cycle. Vermeirsch, H., Van den Broeck, W., Coryn, M., Simoens, P. Theriogenology (2002) [Pubmed]
  15. Uterine androgen receptor mRNA expression in metestrous and anestrous bitches being healthy or suffering from Pyometra. Sauerwein, H., Brandstetter, A., Pfaffl, W.M., Meyer, H.H., Möstl, E., Handler, J., Arbeiter, K. DTW. Dtsch. Tierarztl. Wochenschr. (1998) [Pubmed]
  16. Increased number of neurons expressing androgen receptor in the basolateral amygdala of pathologically aggressive dogs. Jacobs, C., Van Den Broeck, W., Simoens, P. Journal of veterinary medicine. A, Physiology, pathology, clinical medicine. (2006) [Pubmed]
  17. Myocardial protection by verapamil and reperfusion following coronary occlusion. da-Luz, P.L., Silveira, M.C., Chagas, A.C., Pileggi, F. Braz. J. Med. Biol. Res. (1990) [Pubmed]
  18. Expression of the insulin-like growth factor (IGF) system and steroidogenic enzymes in canine testis tumors. Peters, M.A., Mol, J.A., van Wolferen, M.E., Oosterlaken-Dijksterhuis, M.A., Teerds, K.J., van Sluijs, F.J. Reprod. Biol. Endocrinol. (2003) [Pubmed]
  19. Steroids and receptors in canine mammary cancer. Illera, J.C., Pérez-Alenza, M.D., Nieto, A., Jiménez, M.A., Silvan, G., Dunner, S., Peña, L. Steroids (2006) [Pubmed]
  20. Myocardial protection with preconditioning. Li, G.C., Vasquez, J.A., Gallagher, K.P., Lucchesi, B.R. Circulation (1990) [Pubmed]
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