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Characterization of the cytosol androgen receptor of the human prostate.
J Clin Endocrinol Metab. 1983 Jan; 56(1):113-20.JC

Abstract

Direct measurement of the binding of endogenous androgens to the androgen receptor of human tissues has not been possible because of contamination of tissue with traces of plasma proteins, such as testosterone-binding globulin (TeBG), that contain more androgen-binding capacity than does the receptor itself. Molybdate is known to stabilize the 8-9S forms of other steroid hormone receptors. We took advantage of this phenomenon to characterize the androgen receptor of hyperplastic prostates removed at surgery, using sucrose density gradient centrifugation in a vertical rotor. In 10 mM sodium molybdate, the androgen receptor sediments as a distinct 9.2 +/- 0.5S moiety, easily separable from TeBG. Unlike TeBG, the 9S receptor is not removed by absorption with Concanavalin A. [3H]Dihydrotestosterone (3H-labeled 17 beta-hydroxy-5-alpha-androstan-3-one) binding to the 9S receptor is not removed by absorption with Concanavalin A. [3H]Dihydrotestosterone (3H-labeled 17 beta-hydroxy-5 alpha-androstan-3-one) binding to the 9S receptor is not competed for by excess triamcinolone acetonide (9 alpha-fluoro-11 beta, 16 alpha, 17 alpha, 21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetonide) or promegestone (17,21-dimethyl-19-non-pregna-4,9-diene-3,-20-dione), which are known to bind to the progestin receptor. In contrast, [3H]methyltrienolone (3H-labeled 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one) binds to both androgen and progestin receptors, and consequently, the binding of this ligand to the androgen receptor was assessed in the presence of a 500-fold excess of triamcinolone acetonide. The amounts of 9S binding (7.8 and 5.8 fmol/mg protein) are similar for dihydrotestosterone and methyltrienolone. The amount of 9S binding of testosterone to the receptor was also similar to that of dihydrotestosterone, but the affinity of testosterone for the 9S receptor was only a fifth or less of that for dihydrotestosterone. The observation that testosterone binds less avidly than dihydrotestosterone to the receptor may explain the role of dihydrotestosterone formation in androgen physiology.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

6183286

Citation

Wilbert, D M., et al. "Characterization of the Cytosol Androgen Receptor of the Human Prostate." The Journal of Clinical Endocrinology and Metabolism, vol. 56, no. 1, 1983, pp. 113-20.
Wilbert DM, Griffin JE, Wilson JD. Characterization of the cytosol androgen receptor of the human prostate. J Clin Endocrinol Metab. 1983;56(1):113-20.
Wilbert, D. M., Griffin, J. E., & Wilson, J. D. (1983). Characterization of the cytosol androgen receptor of the human prostate. The Journal of Clinical Endocrinology and Metabolism, 56(1), 113-20.
Wilbert DM, Griffin JE, Wilson JD. Characterization of the Cytosol Androgen Receptor of the Human Prostate. J Clin Endocrinol Metab. 1983;56(1):113-20. PubMed PMID: 6183286.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of the cytosol androgen receptor of the human prostate. AU - Wilbert,D M, AU - Griffin,J E, AU - Wilson,J D, PY - 1983/1/1/pubmed PY - 1983/1/1/medline PY - 1983/1/1/entrez SP - 113 EP - 20 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 56 IS - 1 N2 - Direct measurement of the binding of endogenous androgens to the androgen receptor of human tissues has not been possible because of contamination of tissue with traces of plasma proteins, such as testosterone-binding globulin (TeBG), that contain more androgen-binding capacity than does the receptor itself. Molybdate is known to stabilize the 8-9S forms of other steroid hormone receptors. We took advantage of this phenomenon to characterize the androgen receptor of hyperplastic prostates removed at surgery, using sucrose density gradient centrifugation in a vertical rotor. In 10 mM sodium molybdate, the androgen receptor sediments as a distinct 9.2 +/- 0.5S moiety, easily separable from TeBG. Unlike TeBG, the 9S receptor is not removed by absorption with Concanavalin A. [3H]Dihydrotestosterone (3H-labeled 17 beta-hydroxy-5-alpha-androstan-3-one) binding to the 9S receptor is not removed by absorption with Concanavalin A. [3H]Dihydrotestosterone (3H-labeled 17 beta-hydroxy-5 alpha-androstan-3-one) binding to the 9S receptor is not competed for by excess triamcinolone acetonide (9 alpha-fluoro-11 beta, 16 alpha, 17 alpha, 21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetonide) or promegestone (17,21-dimethyl-19-non-pregna-4,9-diene-3,-20-dione), which are known to bind to the progestin receptor. In contrast, [3H]methyltrienolone (3H-labeled 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one) binds to both androgen and progestin receptors, and consequently, the binding of this ligand to the androgen receptor was assessed in the presence of a 500-fold excess of triamcinolone acetonide. The amounts of 9S binding (7.8 and 5.8 fmol/mg protein) are similar for dihydrotestosterone and methyltrienolone. The amount of 9S binding of testosterone to the receptor was also similar to that of dihydrotestosterone, but the affinity of testosterone for the 9S receptor was only a fifth or less of that for dihydrotestosterone. The observation that testosterone binds less avidly than dihydrotestosterone to the receptor may explain the role of dihydrotestosterone formation in androgen physiology. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/6183286/Characterization_of_the_cytosol_androgen_receptor_of_the_human_prostate_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem-56-1-113 DB - PRIME DP - Unbound Medicine ER -