Disease relevance of AR

• We hypothesized that diabetic cardiomyopathy may involve decrements in adrenergic sensitivity, with specific molecular alterations in the beta-adrenergic receptor (beta AR)- G protein- adenylyl cyclase (AC) signal transduction system [1].
• Endothelin type A receptor antagonism restores myocardial perfusion response to adenosine in experimental hypercholesterolemia [2].

High impact information on AR

• Despite regional downregulation of myocardial beta AR number, adenylyl cyclase activity was similar in the ischemic and control beds [3].
• Thus, changes in beta-adrenergic receptor (beta AR) expression should reflect more directly the influence of neurohumoral adrenergic tone, clarifying the manner in which peripheral (neurohumoral) versus primary myocardial factors are operative in decreased beta AR-dependent signal transduction [4].
• Heart rate responsiveness to beta AR stimulation was blunted, with ED50, for isoproterenol increased 133% (p less than 0.001) after development of circulatory congestion [4].
• Biochemical analyses of the beta AR-responsive adenylyl cyclase pathway showed uniform decreases in beta AR number in right atrium, right ventricle, and left ventricle (36-41% decreases, p less than 0.005) [4].
• These data indicate that satellite cells are direct targets for androgen action, and testosterone administration increases immunoreactive AR protein and reduces differentiation of porcine satellite cells in vitro [5].

Biological context of AR

• Characterization of the porcine AR promoter showed two conserved transcription start sites, a consensus sequence of GC-box and a homopurine/homopyrimidine stretch at similar locations compared to the human, rat and mouse as well as sequences similar to androgen response elements (ARE) [6].
• Polymorphisms identified in the present study affect the predicted amino acid sequence as well as consensus transcription factor binding sites and are associated with the allele-specific differences of the AR mRNA transcript level in liver, reinforcing AR as a potential candidate gene for traits related to pig reproduction and performance [6].
• In addition, the antiandrogenic actions of P on the central nervous system, which in this experiment were expressed as a significant decline in reproductive behavior, may be explained by its interference with the retention of the AR in the nucleus [7].
• The purpose of this study was to determine whether androgen receptors (AR) are present in cultured skeletal muscle satellite cells and myotubes and examine the effects of testosterone on satellite cell proliferation and differentiation [5].
• Results identify AR in the pig endometrium during the window of maternal receptivity for implantation and demonstrate the functional, albeit complex, interactions of androgens and estrogens in the regulation of uterine endometrial gene expression and cell growth in vitro [8].

Anatomical context of AR

• The AR mRNA expression levels determined by real-time RT-PCR in various tissues of female pigs were high in ovary (100%) and adrenal gland (83.9% relative to ovary), moderate in uterus (61.6%) and liver (47.4%), and low in pituitary gland (1.3%) as well as in tonsil, muscle, mammary gland, leukocyte and jejunum (less than 1%) [6].
• Immunocytochemical AR staining was confined to the nuclei of satellite cells, myotubes, and muscle-derived fibroblasts [5].
• We assessed the sites, developmental pattern, and hormonal control of androgen receptors (AR) in the rat testis [9].
• Androgen receptors (AR) were determined in cytosol and nuclear extracts of pituitary and neural tissue from intact male guinea pigs by a binding assay using [3H]dihydrotestosterone as ligand [7].
• In animals that underwent a 10 min TCO + 15 min Rep prior to the 60 min TCO + 120 min Rep, IA in both myocardial layers were again highly linearly related with AR, with less steep slopes for both the endocardium (0.63) and epicardium (0.57) (both P < 0.01) [10].

Associations of AR with chemical compounds

• Replacement of T in EDS-treated animals resulted in a pattern of AR immunostaining comparable to that in controls, although staining intensity was reduced [9].
• Methoxyacetic acid administration did not affect the pattern of AR staining [9].
• Addition of an AR antagonist, hydroxyflutamide, generally reversed the proliferative responses invoked by DHT but not the steroidogenic responses [11].
• CONCLUSIONS: ER(alpha), versican core protein and CS side chain epitopes are negatively regulated in prostate stromal tissue by DHT, whilst AR levels are positively regulated [12].
• METHODS: Guinea pig prostate was used to define hormone-induced changes in the expression of androgen (AR) and estrogen (ER(alpha)) receptors, chondroitin sulfate (CS) glycosaminoglycan and core proteins of versican and syndecan-1 [12].

Regulatory relationships of AR

• The CCK-A receptor antagonist L-364,718 was 300-fold more potent than the CCK-B receptor antagonist L-365,260 at inhibiting CCK-8-induced contraction [13].

Other interactions of AR

• To evaluate a role for AR in uterine gene regulation, the levels of mRNAs for insulin-like growth factor-I (IGF-I), proliferative cell nuclear antigen (PCNA), and AR itself were assessed in uterine endometrial explant cultures treated with estradiol-17beta (E), testosterone (T), and 19-nortestosterone (N) [8].
• The relative amounts of AR mRNA in tissue from the largest follicles on days 13, 15, 17, and 19 did not differ; however, amounts of FSHR mRNA in the same follicles were not different between days 13, 15, and 17, but decreased (P < 0.05) by day 19 [14].
• Versican, CS56 epitope, and AR were quantified by image analysis [12].
• These tetrapeptides elicit full agonist responses in stimulating pancreatic amylase release that are effectively blocked by a selective CCK-A receptor antagonist [15].
• Anantin, a competitive blocker of the guanylate cyclase A receptor, significantly reduced the increase in cGMP produced by ANP and BNP, but had no effect on relaxation induced by either peptide [16].

Analytical, diagnostic and therapeutic context of AR

• After 2 h of reperfusion, the area at risk (AR) and infarct size (IS) were determined using standard procedures [17].
• Tissue locations of AR, ER(alpha), CS and the proteoglycans versican and syndecan-1 were determined by immunohistochemistry [12].
• Northern blot analysis demonstrated the approximately 10.5 kilobase AR transcript in endometrium [8].
• RESULTS: AR expression within prostate epithelial and stromal cell nuclei decreased following castration and increased following treatment of castrate animals with dihydrotestosterone (DHT) [12].
• Competitive reverse-transcription PCR (RT-PCR) indicated a stimulatory effect (P<0.01) of E(2) on amounts of AR mRNA in whole endometrium [18].

References