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Partial androgen resistance due to a distinctive qualitative defect of the androgen receptor.
Am J Med Genet. 1987 Jun; 27(2):459-66.AJ

Abstract

Using whole genital skin fibroblasts, we have characterized a novel androgen receptor mutation in a family with partial androgen resistance. The proposita was born with bilateral labioscrotal folds and a single perineal urogenital orifice. Her similarly affected maternal aunt was raised as a female with the support of gonadectomy and vaginoplasty. The mutant androgen receptor has a normal maximum binding capacity (Bmax), but an increased apparent equilibrium dissociation constant (Kd) with 5 alpha-dihydrotestosterone (DHT) and 2 synthetic androgens, methyltrienolone (MT) and mibolerone (MB). Preformed mutant DHT-receptor complexes dissociate (k) at a near-normal rate, but their MT and MB counterparts dissociate twice as quickly as normal. The native free mutant receptor is not more thermolabile than normal, but its recently dissociated counterpart is. Prolonged incubation of the cells with each of the 3 androgens causes the mutant receptor to acquire a normal increment of increased androgen-receptor activity. This androgen-sensitive pattern of misbehavior of the present mutant receptor distinguishes it from those responsible for 3 other families with partial androgen resistance studied previously. These differences will help to identify structure-function domains on the androgen receptor protein, particularly in conjunction with the use of DNA probes to analyze mutations at the X-linked androgen receptor locus.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

3605226

Citation

Pinsky, L, et al. "Partial Androgen Resistance Due to a Distinctive Qualitative Defect of the Androgen Receptor." American Journal of Medical Genetics, vol. 27, no. 2, 1987, pp. 459-66.
Pinsky L, Kaufman M, Levitsky LL. Partial androgen resistance due to a distinctive qualitative defect of the androgen receptor. Am J Med Genet. 1987;27(2):459-66.
Pinsky, L., Kaufman, M., & Levitsky, L. L. (1987). Partial androgen resistance due to a distinctive qualitative defect of the androgen receptor. American Journal of Medical Genetics, 27(2), 459-66.
Pinsky L, Kaufman M, Levitsky LL. Partial Androgen Resistance Due to a Distinctive Qualitative Defect of the Androgen Receptor. Am J Med Genet. 1987;27(2):459-66. PubMed PMID: 3605226.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Partial androgen resistance due to a distinctive qualitative defect of the androgen receptor. AU - Pinsky,L, AU - Kaufman,M, AU - Levitsky,L L, PY - 1987/6/1/pubmed PY - 1987/6/1/medline PY - 1987/6/1/entrez SP - 459 EP - 66 JF - American journal of medical genetics JO - Am. J. Med. Genet. VL - 27 IS - 2 N2 - Using whole genital skin fibroblasts, we have characterized a novel androgen receptor mutation in a family with partial androgen resistance. The proposita was born with bilateral labioscrotal folds and a single perineal urogenital orifice. Her similarly affected maternal aunt was raised as a female with the support of gonadectomy and vaginoplasty. The mutant androgen receptor has a normal maximum binding capacity (Bmax), but an increased apparent equilibrium dissociation constant (Kd) with 5 alpha-dihydrotestosterone (DHT) and 2 synthetic androgens, methyltrienolone (MT) and mibolerone (MB). Preformed mutant DHT-receptor complexes dissociate (k) at a near-normal rate, but their MT and MB counterparts dissociate twice as quickly as normal. The native free mutant receptor is not more thermolabile than normal, but its recently dissociated counterpart is. Prolonged incubation of the cells with each of the 3 androgens causes the mutant receptor to acquire a normal increment of increased androgen-receptor activity. This androgen-sensitive pattern of misbehavior of the present mutant receptor distinguishes it from those responsible for 3 other families with partial androgen resistance studied previously. These differences will help to identify structure-function domains on the androgen receptor protein, particularly in conjunction with the use of DNA probes to analyze mutations at the X-linked androgen receptor locus. SN - 0148-7299 UR - https://www.unboundmedicine.com/medline/citation/3605226/Partial_androgen_resistance_due_to_a_distinctive_qualitative_defect_of_the_androgen_receptor_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1987&volume=27&issue=2&spage=459 DB - PRIME DP - Unbound Medicine ER -