Characterization of the binding of a potent synthetic androgen, methyltrienolone, to human tissues

M. Menon, C. E. Tananis, L. L. Hicks, E. F. Hawkins, M. G. McLoughlin, Patrick Walsh

Research output: Contribution to journalArticle

Abstract

The potent synthetic androgen methyltrienolone (R1881), which does not bind to serum proteins, was utilized to characterize binding to receptors in human androgen responsive tissues. Cytosol extract prepared from hypertrophic prostates (BPH) were utilized as the source of receptor for the initial studies. High affinity binding was detected in the cytosol of 29 of 30 samples of BPH (average number of binding sites, 45.8 ±4.7 fmol/mg of protein; dissociation constant, 0.9 ±0.2 nM). This binding had the characteristics of a receptor: heat lability, precipitability by 0-33% ammonium sulfate and by protamine sulfate, and 8S sedimentation coefficient. High affinity binding was also detected in cytosol prepared from seminal vesicle, epididymis, and genital skin but not in non-genital skin or muscle. However, similar binding was demonstrated in the cytosol of human uterus. The steroid specificities of binding to the cytosol of male tissues of accessory reproduction and of uterus were similar in that progestational agents were more effective competitors than natural androgens. Binding specificities in cytosol prepared from genital skin were distinctly different and were similar to those of ventral prostate from the castrated rat in that dihydrotestosterone was much more potent than progestins in competition. Thus binding of R 1881 to the cytosol of prostate, epididymis and seminal vesicle has some characteristics of binding to a progesterone receptor. When the nuclear extract from BPH was analyzed, high affinity binding was demonstrated that conformed to the specificities of binding to an androgen receptor. Here dihydrotestosterone was aa more potent competitor than progestational agents. Similar patterns of binding were detected in the crude nuclear extracts from seminal vesicle, epididymis, and genital skin but not in uterus, muscle, or non-genital skin. We conclude that the androgen receptor is not demonstrable in the cytosol of prostate, epididymis, or seminal vesicle of non-castrated men but can be measured in the cytosol of genital skin and the nuclear extracts of androgen responsive tissues. Because steroid hormones exert their major influence within the nucleus of target tissues, the measurement of nuclear receptor may provide valuable insight into the regulation of growth of target tissues.

Original languageEnglish (US)
Pages (from-to)150-162
Number of pages13
JournalJournal of Clinical Investigation
Volume61
Issue number1
StatePublished - 1978
Externally publishedYes

Fingerprint

Testosterone Congeners
Metribolone
Cytosol
Seminal Vesicles
Epididymis
Skin
Prostate
Progestins
Uterus
Dihydrotestosterone
Androgen Receptors
Androgens
Steroids
Muscles
Protamines
Ammonium Sulfate
Progesterone Receptors
Cytoplasmic and Nuclear Receptors
Complex Mixtures
Reproduction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Menon, M., Tananis, C. E., Hicks, L. L., Hawkins, E. F., McLoughlin, M. G., & Walsh, P. (1978). Characterization of the binding of a potent synthetic androgen, methyltrienolone, to human tissues. Journal of Clinical Investigation, 61(1), 150-162.

Characterization of the binding of a potent synthetic androgen, methyltrienolone, to human tissues. / Menon, M.; Tananis, C. E.; Hicks, L. L.; Hawkins, E. F.; McLoughlin, M. G.; Walsh, Patrick.

In: Journal of Clinical Investigation, Vol. 61, No. 1, 1978, p. 150-162.

Research output: Contribution to journalArticle

Menon, M, Tananis, CE, Hicks, LL, Hawkins, EF, McLoughlin, MG & Walsh, P 1978, 'Characterization of the binding of a potent synthetic androgen, methyltrienolone, to human tissues', Journal of Clinical Investigation, vol. 61, no. 1, pp. 150-162.
Menon, M. ; Tananis, C. E. ; Hicks, L. L. ; Hawkins, E. F. ; McLoughlin, M. G. ; Walsh, Patrick. / Characterization of the binding of a potent synthetic androgen, methyltrienolone, to human tissues. In: Journal of Clinical Investigation. 1978 ; Vol. 61, No. 1. pp. 150-162.
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abstract = "The potent synthetic androgen methyltrienolone (R1881), which does not bind to serum proteins, was utilized to characterize binding to receptors in human androgen responsive tissues. Cytosol extract prepared from hypertrophic prostates (BPH) were utilized as the source of receptor for the initial studies. High affinity binding was detected in the cytosol of 29 of 30 samples of BPH (average number of binding sites, 45.8 ±4.7 fmol/mg of protein; dissociation constant, 0.9 ±0.2 nM). This binding had the characteristics of a receptor: heat lability, precipitability by 0-33{\%} ammonium sulfate and by protamine sulfate, and 8S sedimentation coefficient. High affinity binding was also detected in cytosol prepared from seminal vesicle, epididymis, and genital skin but not in non-genital skin or muscle. However, similar binding was demonstrated in the cytosol of human uterus. The steroid specificities of binding to the cytosol of male tissues of accessory reproduction and of uterus were similar in that progestational agents were more effective competitors than natural androgens. Binding specificities in cytosol prepared from genital skin were distinctly different and were similar to those of ventral prostate from the castrated rat in that dihydrotestosterone was much more potent than progestins in competition. Thus binding of R 1881 to the cytosol of prostate, epididymis and seminal vesicle has some characteristics of binding to a progesterone receptor. When the nuclear extract from BPH was analyzed, high affinity binding was demonstrated that conformed to the specificities of binding to an androgen receptor. Here dihydrotestosterone was aa more potent competitor than progestational agents. Similar patterns of binding were detected in the crude nuclear extracts from seminal vesicle, epididymis, and genital skin but not in uterus, muscle, or non-genital skin. We conclude that the androgen receptor is not demonstrable in the cytosol of prostate, epididymis, or seminal vesicle of non-castrated men but can be measured in the cytosol of genital skin and the nuclear extracts of androgen responsive tissues. Because steroid hormones exert their major influence within the nucleus of target tissues, the measurement of nuclear receptor may provide valuable insight into the regulation of growth of target tissues.",
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