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Genet."],"published-print":{"date-parts":[[1984,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have studied various properties of the binding of 5\u03b1\u2010dihydrotestosterone (DHT) or the synthetic, nonmetabolizable androgen methyltrienolone (R1881; 17\u03b2\u2010hydroxy\u201017\u03b1\u2010methylestra\u20104, 9,11\u2010trien\u20103\u2010one) to the androgen receptor of genital skin fibroblasts (GSF) from controls and a subject with familial, receptor\u2010positive, partial androgen insensitivity. The mutant cells form R1881\u2010receptor complexes that dissociate 7 times more rapidly than normal at 30\u00b0C, and they do not increase their specific R1881\u2010receptor activity in response to a 72\u2010hr period of incubation with R1881, whereas the cells from normal individuals do so two\u2010 to three\u2010fold. As previously reported [Pinsky et al, 1981; Kaufman et al, 1981], the mutant cells have similar abnormalities with DHT as with R1881. When the patient's cells are incubated for 120 min with varying concentrations (0.05\u20103 nM) of R1881 or DHT, Scatchard analysis shows that their androgen\u2010receptor activity has an apparent equilibrium dissociation constant (K<jats:sub>d<\/jats:sub>) for each ligand that is sixfold greater than that of normal cells (\u223c0.2 nM). Normal GSF have higher, more variable values of K<jats:sub>d<\/jats:sub> (0.3\u20131.8 nM) for either ligand after 30 compared to 120 min of incubation, and the 60\u2010min values are intermediate. This explains why we previously reported that the patient's cells had a 30\u2010min K<jats:sub>d<\/jats:sub> for DHT in the normal range [Pinsky et al, 1981]. Sucrose gradient centrifugation of mutant GSF cytosol incubated with DHT in the presence of 10 mM sodium molybdate yields a normal 6.5\u20138S peak of DHT\u2010receptor complexes.<\/jats:p><jats:p>From these data we conclude that (i) normal GSF form initial, low\u2010affinity androgen\u2010receptor complexes that are transformed into one (or more) higher affinity (? activated) states by a process that depends on time and initial concentration of androgen; (ii) the subject's GSF can form low\u2010affinity androgen\u2010receptor complexes but cannot generate the normal high\u2010affinity state of the complexes, and this lack precludes augmentation of their androgen\u2010receptor activity in response to prolonged incubation with either androgen; and (iii) failure of molybdate to stabilize the androgen\u2010receptor activity in GSF cytosol is not a more sensitive indicator of structurally altered androgen\u2010receptor proteins than are other qualities described heretofore.<\/jats:p>","DOI":"10.1002\/ajmg.1320180319","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T19:46:02Z","timestamp":1118519162000},"page":"493-507","source":"Crossref","is-referenced-by-count":13,"title":["Familial external genital ambiguity due to a transformation defect of androgen\u2010receptor complexes that is expressed with 5\u03b1\u2010dihydrotestosterone and the synthetic androgen methyltrienolone"],"prefix":"10.1002","volume":"18","author":[{"given":"Morris","family":"Kaufman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Pinsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adria","family":"Bowin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary W. S.","family":"Au","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,3]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.3.891"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-55-1-61"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(81)90209-0"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110839"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109624"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-55-3-465"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111052"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.0940415"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(83)90077-8"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320040410"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/293735a0"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(83)90055-9"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(82)90048-X"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108478"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-53-6-1243"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.4.1469"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.10.6339"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-104-2-500"},{"key":"e_1_2_1_21_1","unstructured":"PinskyL KaufmanM KillingerDW BurkoB ShatzD Volp\u00e9R(1984): Human minimal androgen insensitivity with normal dihydrotestosterone\u2010binding capacity in cultured genital skin fibroblasts: Evidence for an androgen\u2010selective qualitative abnormality of the receptor.Am J Hum Genet(in press)."},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1139\/o83-097"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320100111"},{"key":"e_1_2_1_24_1","first-page":"563","article-title":"GM1\u2010gangliosidosis in skin fibroblast culture: Enzymatic differences between types 1 and 2 and observations on a third variant","volume":"26","author":"Pinsky L","year":"1974","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1949.tb27297.x"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(83)90045-X"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"8856","DOI":"10.1016\/S0021-9258(17)38319-9","article-title":"Estradiol\u2010binding kinetics of the activated and nonactivated estrogen receptor","volume":"252","author":"Weichman BM","year":"1977","journal-title":"J Biol Chem"}],"container-title":["American Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.1320180319","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.1320180319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T20:19:38Z","timestamp":1697746778000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.1320180319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,7]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1984,7]]}},"alternative-id":["10.1002\/ajmg.1320180319"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.1320180319","archive":["Portico"],"relation":{},"ISSN":["0148-7299","1096-8628"],"issn-type":[{"value":"0148-7299","type":"print"},{"value":"1096-8628","type":"electronic"}],"subject":[],"published":{"date-parts":[[1984,7]]}}}