{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T07:07:35Z","timestamp":1648883255495},"reference-count":16,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations of the androgen receptor (AR) cause defects in virilization and can result in a spectrum of phenotypic abnormalities of male sexual development that includes patients with a completely female phenotype (complete testicular feminization) and individuals with less severe defects of virilization, such as Reifenstein syndrome. These phenotypes are not specific for mutations of the AR gene, however, and defects in other genes can also result in similar abnormalities of male development. For this reason, the diagnosis of an AR defect is laborious and requires data from endocrine studies, the family history, and in vitro binding experiments.<\/jats:p><jats:p>To assist in the evaluation of patients with possible AR defects, we previously employed the use of a recombinant adenovirus to deliver an androgen-responsive gene into fibroblast cultures to assay AR function in normal subjects and patients with complete forms of androgen resistance. Although these studies demonstrated measurable differences between these two groups of subjects, we did not assay samples from patients with partial defects of androgen action. In the current study, we have modified this method to examine AR function in three groups of patients with known or suspected defects of AR function: patients with Reifenstein syndrome, patients with spinobulbar muscular atrophy, and patients with severe forms of isolated hypospadias. When assayed using this method, the AR function of patients with Reifenstein syndrome was intermediate between that of normal control subjects and that of patients with complete testicular feminization. Using the parameters established by the aforementioned experiments, we found that defective AR function can be detected in fibroblasts established from patients with spinobulbar muscular atrophy and in some patients with severe forms of isolated hypospadias, including two with a normal AR gene sequence. These results suggest that this method may have some utility in screening samples to detect defects of AR function, particularly when viewed in the context of other AR assays results.<\/jats:p>","DOI":"10.1210\/jcem.82.6.3966","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:43Z","timestamp":1389200503000},"page":"1944-1948","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Androgen Receptor Function in Genital Skin Fibroblasts Using a Recombinant Adenovirus to Deliver an Androgen-Responsive Reporter Gene1"],"prefix":"10.1210","volume":"82","author":[{"given":"Michael J.","family":"McPhaul","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235; and the Department of Internal Medicine, University of Bonn, Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Udo","family":"Schweikert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235; and the Department of Internal Medicine, University of Bonn, Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane R.","family":"Allman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235; and the Department of Internal Medicine, University of Bonn, Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613582063200_R1","author":"Griffin","year":"1995"},{"key":"2020071613582063200_R2","first-page":"2697","article-title":"Mutations of the androgen receptor coding sequence are infrequent in patients with isolated hypospadias.","volume":"80","author":"A\u0301llera","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613582063200_R3","doi-asserted-by":"crossref","first-page":"26063","DOI":"10.1016\/S0021-9258(19)74278-1","article-title":"The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures.","volume":"268","author":"McPhaul","year":"1993","journal-title":"J Biol Chem"},{"key":"2020071613582063200_R4","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1172\/JCI116093","article-title":"Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene.","volume":"90","author":"McPhaul","year":"1992","journal-title":"J Clin Invest"},{"key":"2020071613582063200_R5"},{"key":"2020071613582063200_R6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/352077a0","article-title":"Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy.","volume":"352","author":"LaSpada","year":"1991","journal-title":"Nature"},{"key":"2020071613582063200_R7","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1172\/JCI113930","article-title":"Intracellular and nuclear binding of[ 3H]dihydrotestosterone in cultured genital skin fibroblasts of patients with severe hypospadias.","volume":"83","author":"Schweikert","year":"1989","journal-title":"J Clin Invest"},{"key":"2020071613582063200_R8","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1210\/mend-5-2-300","article-title":"An adenoviral vector system for functional identification of nuclear receptor ligands.","volume":"5","author":"Shih","year":"1991","journal-title":"Mol Endocrinol"},{"key":"2020071613582063200_R9","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1172\/JCI117507","article-title":"Amino acid substitutions in the hormone-binding domain of the human androgen receptor alter the stability of the hormone receptor complex.","volume":"94","author":"Marcelli","year":"1994","journal-title":"J Clin Invest"},{"key":"2020071613582063200_R10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ng1093-184","article-title":"Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy.","volume":"5","author":"Mhatre","year":"1993","journal-title":"Nat Genet"},{"key":"2020071613582063200_R11","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1212\/WNL.43.4.791","article-title":"Kennedy\u2019s disease: a clinicopathologic correlation with mutations in the androgen receptor gene.","volume":"43","author":"Amato","year":"1993","journal-title":"Neurology"},{"key":"2020071613582063200_R12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0960-0760(96)00097-0","article-title":"Transcriptional activation and transient expression of the human androgen receptor.","volume":"59","author":"Gao","year":"1996","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071613582063200_R13","first-page":"289","article-title":"The incidence of congenital disease and defects in a south Swedish population.","volume":"2","year":"1951","journal-title":"Acta Genet"},{"key":"2020071613582063200_R14","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/0002-9610(58)90932-2","article-title":"The incidence of congenital anomalies discovered in the neonatal period.","volume":"96","author":"Shapiro","year":"1958","journal-title":"Am J Surg"},{"key":"2020071613582063200_R15","first-page":"1527","article-title":"Reduced androgen receptor gene expression with first exon CAG repeat expansion.","volume":"10","author":"Choong","year":"1996","journal-title":"Mol Endocrinol"},{"key":"2020071613582063200_R16","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1210\/jcem-55-3-465","article-title":"Qualitative receptor defects in families with androgen resistance: failure of stabilization of the fibroblast cytosol androgen receptor.","volume":"55","author":"Griffin","year":"1982","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/82\/6\/1944\/10405607\/jcem1944.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/82\/6\/1944\/10405607\/jcem1944.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T23:43:55Z","timestamp":1647906235000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/82\/6\/1944\/2656725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,6,1]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1997,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jcem.82.6.3966","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,6,1]]}}}