Reduction of testosterone availability to 5α-reductase by human sex hormone-binding globulin in the rat ventral prostate gland in vivo

The Prostate ◽  
1990 ◽  
Vol 17 (4) ◽  
pp. 281-291 ◽  
Author(s):  
Sean A. Ellison ◽  
William M. Pardridge
1971 ◽  
Vol 123 (4) ◽  
pp. 619-628 ◽  
Author(s):  
W. I. P. Mainwaring ◽  
F. R. Mangan ◽  
B. M. Peterken

1. By using ultrasonic treatment in media of high ionic strength, the RNA polymerase activities associated with prostatic nuclei and nucleoli can be completely solubilized. Such enzyme preparations are entirely dependent on the provision of added DNA for full activity. 2. The solubilized enzymes from the nucleolar and extranucleolar regions can be separated by ion-exchange chromatography. 3. Based on differences in the optimum DNA templates, pH optima and the effects of ammonium sulphate on the activities in vitro, Mn2+- and Mg2+-specific enzymes are associated with both the nucleolar and extranucleolar regions of prostatic nuclei. 4. Androgenic hormones administered in vivo have a particularly pronounced effect on the activity of Mg2+-dependent enzyme associated with the isolated prostatic nucleolus. 5. Time-course experiments in vivo show that androgens induce a rapid stimulation of the solubilized Mg2+-dependent nucleolar enzyme before a pronounced activation of nucleolar chromatin can be measured. 6. The implications of these findings to the mechanism of action of androgenic steroids are discussed.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Michaël R. Laurent ◽  
Geoffrey L. Hammond ◽  
Marco Blokland ◽  
Ferran Jardí ◽  
Leen Antonio ◽  
...  

1971 ◽  
Vol 125 (1) ◽  
pp. 81-91 ◽  
Author(s):  
J. E. Belham ◽  
G. E. Neal

Recent reports have indicated that the prior metabolism of testosterone by the secondary sexual tissues may be necessary for its androgenic effect. The effects of two anti-androgens, diethylstilboestrol and cyproterone acetate (17α-acetoxy-6-chloro-1,2α-methylenepregna-4,6-diene-3,20-dione) used in the chemotherapy of human prostatic carcinoma, have been examined on both the metabolism of testosterone and the retention of its metabolites by the rat ventral prostate gland. Cyproterone acetate was found to inhibit the retention of labelled metabolites of [3H]-testosterone by prostatic nuclei, both in vivo and in vitro. This inhibition appeared to be competitive. In contrast with its effect on nuclear retention of metabolites of testosterone, cyproterone acetate had no significant effect on the metabolism of [3H]testosterone by rat ventral prostate tissue. Diethylstilboestrol similarly had little effect on the metabolism of [3H]testosterone by prostatic tissue, although it did appear partially to inhibit its initial metabolism in all the incubation systems used. Diethylstilboestrol inhibited the nuclear retention of dihydrotestosterone when both [3H]testosterone and diethylstilboestrol were injected intraperitoneally in vivo, but had no effect on dihydrotestosterone retention when both testosterone and diethylstilboestrol were supplied directly to the prostate either in vivo or in vitro. It was concluded that if diethylstilboestrol has an anti-androgenic effect at the level of the target organ as distinct from its effect on androgen production by the testes, then it is probably due to a mechanism differing from that of cyproterone acetate.


1971 ◽  
Vol 125 (1) ◽  
pp. 285-295 ◽  
Author(s):  
W. I. P. Mainwaring ◽  
Brenda M. Peterken

1. A system has been developed for the specific transfer of [3H]dihydrotestosterone–receptor complexes into prostatic chromatin in vitro. 2. Under optimum conditions the overall transfer of [3H]dihydrotestosterone into purified chromatin in this reconstituted system is entirely consistent with the results obtained in whole tissue both in vivo and in vitro. 3. The transfer of [3H]dihydrotestosterone into chromatin is tissue-specific and maximal into chromatin isolated from androgen-dependent tissues. 4. The tissue specificity is maintained at two levels: first, in the presence of specific cytoplasmic androgen-receptor proteins; secondly, by the nature and composition of the chromatin itself. 5. Evidence is presented that androgenic steroids in vivo may maintain the tissue-specific nature of chromatin in androgen-dependent tissues by the selective induction of nuclear protein synthesis. 6. The relevance of these findings to the mechanism of action of androgenic steroids is discussed.


1989 ◽  
Vol 12 (7) ◽  
pp. 489-493 ◽  
Author(s):  
L. Bartalena ◽  
E. Martino ◽  
A. Pacchiarotti ◽  
S. Balzano ◽  
M. Falcone ◽  
...  

1977 ◽  
Vol 86 (2) ◽  
pp. 430-436 ◽  
Author(s):  
Arne Victor ◽  
Erik Weiner ◽  
Elof D. B. Johansson

ABSTRACT In order to investigate the effect of changes in sex hormone binding globulin (SHBG) levels on d-norgestrel (d-Ng) levels in plasma, the plasma levels of SHBG and d-Ng were studied during one treatment cycle in 6 women on oral contraceptives containing d-Ng and ethinyloestradiol (EOe2) and in 3 women using subcutaneous silastic rods containing d-Ng concomitantly taking EOe2 for three weeks. A significant positive correlation between the SHBG and d-Ng levels was found in 7 of the 9 subjects studied. The results provide evidence for an in vivo binding of d-Ng to SHBG, a SHBG influence on the metabolic clearance rate of d-Ng and consequently a dependence of the plasma levels of d-Ng on the SHBG concentrations in the plasma. These findings support the concept that the clinically and biochemically observed anti-oestrogenic/androgenic effects observed in women on d-Ng containing medication are due to a displacement of testosterone from SHBG by d-Ng.


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