Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
|
pubmed:dateCreated |
1982-4-12
|
pubmed:abstractText |
Partially-purified 5 alpha-dihydrotestosterone-receptor (DHT-R) complexes, extracted from normal genital skin fibrolasts (GSF) previously labelled with [3H]DHT, dissociate with monophasic kinetics and dissociation rate constants (k-2) of 10, 6, 3 and 2 x 10(-3) min-1 at 40, 37, 32 and 29 degrees C, respectively. An Arrhenius plot yields an activation energy of 28 kcal/mole. We studied 2 subjects who have constitutional androgen insensitivity (AI) despite a normal level of specific DHT-R activity in their GSF. Subject 1 has complete AI and unambiguous female external genitalia; subject 2 has partial AI and had ambiguous external genitalia at birth. In contrast to normal, the DHT-R complexes extracted from the GSF of these 2 subjects dissociate with biphasic kinetics. At 37 degrees C the k-1 of their early ('fast') component is 21 +/- 0.4(+/-SEM) x 10(-3) min-1(n = 7), while that of their late ('slow') component (k-2) is 7.8 +/- 0.3 x 10(-3) min-1 (n = 7). The latter value is very similar to the single k-2 (6.1 +/- 0.1 x 10(-3) min-1, n = 9) of the DHT-R complexes extracted from normal fibroblasts. When dissociation of DHT-R complexes is studied with intact fibroblasts, monophasic kinetics are observed for both the normal and mutant subjects. A k-1 of 18 x 10(-3) min-1 was previously observed for both mutant subjects at 37 degrees C (normal: K-2, 5.9 +/- 0.3 x 10(-3) min-1, n = 15). At 40 degrees C subject 1 has a rate constant of 25 while that of subject 2 is 50 x 10(-3) min-1(normal: 10 x 10(-3) min-1). An Arrhenius plot of the results from subject 1 yields an activation energy of 18 kcal/mole. The 2 sets of data suggest that inability of DHT-R complexes to transform from a rapidly dissociating to a slowly-dissociating form within intact target cells is a marker of genetic mutations that alter the androgen receptor and thereby cause certain types of partial of complete AI.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0303-7207
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
25
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
151-62
|
pubmed:dateRevised |
2010-11-18
|
pubmed:meshHeading |
pubmed-meshheading:7056433-Androgen-Insensitivity Syndrome,
pubmed-meshheading:7056433-Cells, Cultured,
pubmed-meshheading:7056433-Dihydrotestosterone,
pubmed-meshheading:7056433-Disorders of Sex Development,
pubmed-meshheading:7056433-Female,
pubmed-meshheading:7056433-Fibroblasts,
pubmed-meshheading:7056433-Genitalia,
pubmed-meshheading:7056433-Humans,
pubmed-meshheading:7056433-Kinetics,
pubmed-meshheading:7056433-Male,
pubmed-meshheading:7056433-Models, Biological,
pubmed-meshheading:7056433-Mutation,
pubmed-meshheading:7056433-Radioligand Assay,
pubmed-meshheading:7056433-Receptors, Androgen,
pubmed-meshheading:7056433-Receptors, Steroid
|
pubmed:year |
1982
|
pubmed:articleTitle |
Defective activation of androgen-receptor complexes: a marker of androgen insensitivity.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|