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A study of androgen-resistant subjects indicates that the 6.7 pI/56 kDa protein in genital skin fibroblasts is related to the androgen receptor.
Clin Invest Med. 1988 Feb; 11(1):22-33.CI

Abstract

Two-dimensional gel electrophoresis of cultured human skin fibroblast lysates reveals a silver-stained "spot" of molecular mass 56 kilodaltons (kDa) and isoelectric point (pI) 6.7, occasionally as part of a doublet with a minor pI 6.5 partner. Its presence in each of 23 genital skin fibroblast strains (6 labium majus, 17 prepuce) and its absence in 30 of 32 control non-genital skin fibroblast strains accords with the 3-fold greater concentration of androgen-receptor activity in the former. However, the size and intensity of the spot do not change when cells are preincubated for 48 hours with 3 nM methyltrienolone (MT, a non-metabolizable androgen), and it is pulse-labeled with [35S]methionine to an autoradiographically equal extent, with or without incubation in 3 nM MT for 2 or 16 hours. Furthermore, the protein identified by the spot is found in the labium majus skin fibroblast strains from 2 of 12 unrelated subjects with complete androgen resistance due to negligible androgen-receptor activity, but it is absent from those of 2 others who have the same phenotype despite a normal level of qualitatively abnormal androgen-receptor activity. Hence, it is very unlikely to be an androgen-induced protein, and it cannot be a functional version of the androgen receptor itself. Its absence in 12 of 14 labium majus strains of subjects with complete androgen resistance, regardless of 5 alpha-reductase activities, indicates that it is neither a constitutive cytotypic marker of genital skin fibroblast differentiation nor a reflection of that enzyme. When intact prepuce fibroblasts are covalently labeled by photolysis with 50 nM [3H]MT, the only specific labeling detectable after two-dimensional electrophoresis is in the 6.7 and 6.5 pI doublet of the 56 kDa protein. Considering the sensitivity of silver staining and the incomplete concordance between the androgen-receptor activity of a strain and the size/intensity of its 6.7 pI/56 kDa spot on the gels, we postulate the latter to be a comparatively abundant androgen-binding protein that is causally related to the androgen receptor. The precise nature of this relation remains to be elucidated by use of novel immunologic and/or nucleic acid probes for this protein and for the mature androgen receptor. In any event, the presence or absence of the 6.7 pI/56 kDa protein in genital skin fibroblast lysates is a new marker of genetic heterogeneity within the class of complete androgen resistance.

Authors+Show Affiliations

Department of Biochemistry, University of Manitoba, Winnipeg.No affiliation info availableNo affiliation info availableNo 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

3259169

Citation

Nickel, B, et al. "A Study of Androgen-resistant Subjects Indicates That the 6.7 pI/56 kDa Protein in Genital Skin Fibroblasts Is Related to the Androgen Receptor." Clinical and Investigative Medicine. Medecine Clinique Et Experimentale, vol. 11, no. 1, 1988, pp. 22-33.
Nickel B, Schwartz A, Rosenmann E, et al. A study of androgen-resistant subjects indicates that the 6.7 pI/56 kDa protein in genital skin fibroblasts is related to the androgen receptor. Clin Invest Med. 1988;11(1):22-33.
Nickel, B., Schwartz, A., Rosenmann, E., Kaufman, M., Pinsky, L., & Wrogemann, K. (1988). A study of androgen-resistant subjects indicates that the 6.7 pI/56 kDa protein in genital skin fibroblasts is related to the androgen receptor. Clinical and Investigative Medicine. Medecine Clinique Et Experimentale, 11(1), 22-33.
Nickel B, et al. A Study of Androgen-resistant Subjects Indicates That the 6.7 pI/56 kDa Protein in Genital Skin Fibroblasts Is Related to the Androgen Receptor. Clin Invest Med. 1988;11(1):22-33. PubMed PMID: 3259169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A study of androgen-resistant subjects indicates that the 6.7 pI/56 kDa protein in genital skin fibroblasts is related to the androgen receptor. AU - Nickel,B, AU - Schwartz,A, AU - Rosenmann,E, AU - Kaufman,M, AU - Pinsky,L, AU - Wrogemann,K, PY - 1988/2/1/pubmed PY - 1988/2/1/medline PY - 1988/2/1/entrez SP - 22 EP - 33 JF - Clinical and investigative medicine. Medecine clinique et experimentale JO - Clin Invest Med VL - 11 IS - 1 N2 - Two-dimensional gel electrophoresis of cultured human skin fibroblast lysates reveals a silver-stained "spot" of molecular mass 56 kilodaltons (kDa) and isoelectric point (pI) 6.7, occasionally as part of a doublet with a minor pI 6.5 partner. Its presence in each of 23 genital skin fibroblast strains (6 labium majus, 17 prepuce) and its absence in 30 of 32 control non-genital skin fibroblast strains accords with the 3-fold greater concentration of androgen-receptor activity in the former. However, the size and intensity of the spot do not change when cells are preincubated for 48 hours with 3 nM methyltrienolone (MT, a non-metabolizable androgen), and it is pulse-labeled with [35S]methionine to an autoradiographically equal extent, with or without incubation in 3 nM MT for 2 or 16 hours. Furthermore, the protein identified by the spot is found in the labium majus skin fibroblast strains from 2 of 12 unrelated subjects with complete androgen resistance due to negligible androgen-receptor activity, but it is absent from those of 2 others who have the same phenotype despite a normal level of qualitatively abnormal androgen-receptor activity. Hence, it is very unlikely to be an androgen-induced protein, and it cannot be a functional version of the androgen receptor itself. Its absence in 12 of 14 labium majus strains of subjects with complete androgen resistance, regardless of 5 alpha-reductase activities, indicates that it is neither a constitutive cytotypic marker of genital skin fibroblast differentiation nor a reflection of that enzyme. When intact prepuce fibroblasts are covalently labeled by photolysis with 50 nM [3H]MT, the only specific labeling detectable after two-dimensional electrophoresis is in the 6.7 and 6.5 pI doublet of the 56 kDa protein. Considering the sensitivity of silver staining and the incomplete concordance between the androgen-receptor activity of a strain and the size/intensity of its 6.7 pI/56 kDa spot on the gels, we postulate the latter to be a comparatively abundant androgen-binding protein that is causally related to the androgen receptor. The precise nature of this relation remains to be elucidated by use of novel immunologic and/or nucleic acid probes for this protein and for the mature androgen receptor. In any event, the presence or absence of the 6.7 pI/56 kDa protein in genital skin fibroblast lysates is a new marker of genetic heterogeneity within the class of complete androgen resistance. SN - 0147-958X UR - https://www.unboundmedicine.com/medline/citation/3259169/A_study_of_androgen_resistant_subjects_indicates_that_the_6_7_pI/56_kDa_protein_in_genital_skin_fibroblasts_is_related_to_the_androgen_receptor_ DB - PRIME DP - Unbound Medicine ER -