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Reduced affinity of the androgen receptor for 5 alpha-dihydrotestosterone but not methyltrienolone in a form of partial androgen resistance. Studies on cultured genital skin fibroblasts.
J Clin Invest. 1985 Apr; 75(4):1291-6.JCI

Abstract

We have studied a child with posterior labial fusion, clitoral phallus, female urethra, and a short, blind vagina born to a mother with decreased axillary and pubic hair. Her karyotype is 46,XY. At 2 yr of age, the child's basal level of plasma testosterone was less than 0.35 nM and after human chorionic gonadotropin stimulation, it rose to 2.6. Testis and epididymis histology were normal. Her cultured genital (labial) skin fibroblasts have normal testosterone 5 alpha-reductase activity, and metabolize 5 alpha-dihydrotestosterone (DHT) normally, but they do not augment (up-regulate) their basal androgen-receptor binding activity during prolonged incubation with DHT. With DHT, the androgen receptor in her genital skin fibroblasts has a normal binding capacity (maximum binding capacity = 25 fmol/mg protein), but an increased rate constant of dissociation (k = 11.6 X 10(-3) min-1; normal, 6 +/- 1.2 (+/- SD)), and a decreased apparent equilibrium binding affinity (Kd = 0.6 nM; normal, 0.22 +/- 0.09) that is evident in the results of 2-h assays but not of those lasting 0.5 h. With the synthetic androgen, methyltrienolone, all three binding properties of the receptor are normal, and her receptor activity up-regulates normally. We interpret these results to mean that the subject has a ligand-selective defect in the time-dependent transformation of initial, low-affinity androgen-receptor complexes to serial states of higher affinity, presumably as the result of a structural mutation at the X-linked locus that encodes the androgen receptor protein.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

3872888

Citation

Pinsky, L, et al. "Reduced Affinity of the Androgen Receptor for 5 Alpha-dihydrotestosterone but Not Methyltrienolone in a Form of Partial Androgen Resistance. Studies On Cultured Genital Skin Fibroblasts." The Journal of Clinical Investigation, vol. 75, no. 4, 1985, pp. 1291-6.
Pinsky L, Kaufman M, Chudley AE. Reduced affinity of the androgen receptor for 5 alpha-dihydrotestosterone but not methyltrienolone in a form of partial androgen resistance. Studies on cultured genital skin fibroblasts. J Clin Invest. 1985;75(4):1291-6.
Pinsky, L., Kaufman, M., & Chudley, A. E. (1985). Reduced affinity of the androgen receptor for 5 alpha-dihydrotestosterone but not methyltrienolone in a form of partial androgen resistance. Studies on cultured genital skin fibroblasts. The Journal of Clinical Investigation, 75(4), 1291-6.
Pinsky L, Kaufman M, Chudley AE. Reduced Affinity of the Androgen Receptor for 5 Alpha-dihydrotestosterone but Not Methyltrienolone in a Form of Partial Androgen Resistance. Studies On Cultured Genital Skin Fibroblasts. J Clin Invest. 1985;75(4):1291-6. PubMed PMID: 3872888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced affinity of the androgen receptor for 5 alpha-dihydrotestosterone but not methyltrienolone in a form of partial androgen resistance. Studies on cultured genital skin fibroblasts. AU - Pinsky,L, AU - Kaufman,M, AU - Chudley,A E, PY - 1985/4/1/pubmed PY - 1985/4/1/medline PY - 1985/4/1/entrez SP - 1291 EP - 6 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 75 IS - 4 N2 - We have studied a child with posterior labial fusion, clitoral phallus, female urethra, and a short, blind vagina born to a mother with decreased axillary and pubic hair. Her karyotype is 46,XY. At 2 yr of age, the child's basal level of plasma testosterone was less than 0.35 nM and after human chorionic gonadotropin stimulation, it rose to 2.6. Testis and epididymis histology were normal. Her cultured genital (labial) skin fibroblasts have normal testosterone 5 alpha-reductase activity, and metabolize 5 alpha-dihydrotestosterone (DHT) normally, but they do not augment (up-regulate) their basal androgen-receptor binding activity during prolonged incubation with DHT. With DHT, the androgen receptor in her genital skin fibroblasts has a normal binding capacity (maximum binding capacity = 25 fmol/mg protein), but an increased rate constant of dissociation (k = 11.6 X 10(-3) min-1; normal, 6 +/- 1.2 (+/- SD)), and a decreased apparent equilibrium binding affinity (Kd = 0.6 nM; normal, 0.22 +/- 0.09) that is evident in the results of 2-h assays but not of those lasting 0.5 h. With the synthetic androgen, methyltrienolone, all three binding properties of the receptor are normal, and her receptor activity up-regulates normally. We interpret these results to mean that the subject has a ligand-selective defect in the time-dependent transformation of initial, low-affinity androgen-receptor complexes to serial states of higher affinity, presumably as the result of a structural mutation at the X-linked locus that encodes the androgen receptor protein. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/3872888/Reduced_affinity_of_the_androgen_receptor_for_5_alpha_dihydrotestosterone_but_not_methyltrienolone_in_a_form_of_partial_androgen_resistance__Studies_on_cultured_genital_skin_fibroblasts_ L2 - https://doi.org/10.1172/JCI111829 DB - PRIME DP - Unbound Medicine ER -