scholarly journals The androgenic regulation of superhelical-DNA nicking-closing enzyme in rat ventral prostate

1981 ◽  
Vol 196 (1) ◽  
pp. 195-202 ◽  
Author(s):  
J D Filipenko ◽  
P S Rennie ◽  
N Bruchovsky

The activity of superhelical-DNA nicking-closing enzyme (NC enzyme) was measured in nuclei from rat ventral prostate by a fluorimetric assay based on the binding of ethidium bromide to supercoiled phage-PM2 DNA. The nuclear concentration of NC-enzyme activity declined rapidly after castration, although this response could be prevented by daily administration of dihydrotestosterone. The low NC-enzyme activity in involuted prostates (10% of normal) was restored to normal after 8-10 days of treatment with androgen. In the regenerating prostate the time course of restoration of NC-enzyme activity was not in phase with that of DNA synthesis. Examination of nucleosome repeat lengths and the arrangement of nucleosomes along the chromatin fibre revealed no differences in the structural organization of chromatin in prostates with high or low NC-enzyme activity. Together, these results suggest that the major role of NC enzyme is related to the onset and maintenance of differentiation in the prostate and that the activity of this enzyme is not expressed through gross alterations in chromatin structure.

1992 ◽  
Vol 148 (2 Part 1) ◽  
pp. 432-440 ◽  
Author(s):  
Frank S. Darras ◽  
Chung Lee ◽  
Shankar Huprikar ◽  
Alfred W. Rademaker ◽  
John T. Grayhack

1969 ◽  
Vol 115 (2) ◽  
pp. 241-247 ◽  
Author(s):  
A E Pegg ◽  
H G Williams-Ashman

A soluble enzyme preparation catalysing the release of adenine from 5′-methylthioadenosine was purified some 30-fold from extracts of the rat ventral prostate. This reaction was completely dependent on addition of inorganic phosphate ions to the assay medium. This absolute requirement for phosphate ions suggests a phosphorolytic cleavage mechanism. After acid treatment, the other product of the reaction appeared to be 5-methylthioribose. The actions of some other well-characterized enzymes of nucleoside metabolism of 5′-methylthioadenosine were also investigated; purified purine nucleoside phosphorylases from calf spleen and human erythrocytes did not attack 5′-methylthioadenosine. The role of 5′-methylthioadenosine in mammalian tissues is discussed.


1972 ◽  
Vol 54 (3) ◽  
pp. 375-385 ◽  
Author(s):  
W. E. FARNSWORTH

SUMMARY The purposes of this study were: (1) to determine if a (Na+ + K+)-dependent, ouabain-sensitive, androgen-responsive ATPase is present in the microsomal fraction of the human prostate as it is in the rat ventral prostate; (2) to determine the degree and nature of interaction and interdependence of the ATPase with the steroid-binding and steroid-metabolizing activities of the prostate and, also, with the histological characteristics of the gland. The results indicate that ATPase which shows particular responsiveness to 5α-dihydrotestosterone, 5α-androstane-3α,17β-diol and dehydroepiandrosterone is present. The microsomes, which contain this enzymic activity, show relatively high affinity for the active steroids and for oestradiol-17β. The intrinsic steroid-sensitive, cation-dependent ATPase activity varies widely from gland to gland in parallel with the steroid binding and 3α-hydroxysteroid dehydrogenase activity. In comparisons of the enzymatic complements of glands with different histological features, the concentration of 4-en-3-oxosteroid-5α-reductase activity in tissue showing predominantly epithelial hyperplasia was greater than that in normal or carcinomatous glands or glands with stromal hypertrophy. The possible role of the ATPase as a mediator of hormonal stimulation, and the implications of the findings to an understanding of the development of benign prostatic hypertrophy, are discussed.


1975 ◽  
Vol 152 (1) ◽  
pp. 1-16 ◽  
Author(s):  
P S Rennie ◽  
E K Symes ◽  
W J Mainwaring

1. The restoration of mitosis and growth of the prostate gland of castrated animals by androgens provides a favourable experimental system for studying the hormonal regulation of enzymes engaged in DNA replication. 2. Many DNA polymerase activities were identified in the prostate gland, but only a 9S form with a particular preference for denatured DNA as template was conspicuously enhanced by androgenic stimulation. 3. Thymidine kinase also provided a sensitive indicator of the hormonal regulation of DNA replication, and on electrophoretic criteria, one discrete form of the enzyme appeared precisely with the onset of mitoris. 4. Evidence is presented to support the view that DNA ligase activity is intimately associated in the process of DNA replication in the prostate gland. 5. A spectrum of deoxyribonuclease activities is present in the prostate gland, but only one form (pI7.0) can safely be said to be implicated in the process of DNA replication. 6. Androgenic stimulation of the prostate gland leads to the appearance of a component capable of denaturing or unwinding prostate DNA. This component is seemingly distinct from RNA or DNA polymerase activities on the basis of several distince physicochemical characteristics. 7. The conspicuous feature of all the changes in enzyme activities evoked by androgens in the prostate gland is their acute tissue- and steroid-specificity. Such changes could not be mimicked in liver or spleen and the regulatory role of androgens could not be simulated by other classes of steroid hormones. Particularly on the basis of studies with the anti-androgen cyproterone acetate, it is concluded that the changes are initially mediated by the androgen-receptor system and the high-affinity binding of 5α-dihydrotestosterone in the prostate gland. 8. The results are discussed in the context of the mechanism of action of androgens.


1976 ◽  
Vol 81 (2) ◽  
pp. 398-408 ◽  
Author(s):  
Risto Johansson

ABSTRACT The actions of prolactin, insulin and cortisol on the conversion of testosterone to dihydrotestosterone in the cultured rat ventral prostate were examined in conditions in which they have been demonstrated to act synergistically with testosterone on the macromolecule synthesis of the prostate. On the other hand oestradiol, progesterone and cyproterone were tested similarly in conditions where they have been shown to be effective antiandrogens. The metabolism of testosterone to dihydrotestosterone was found to be extremely rapid and approximately 70 % of the radioactive steroids in the tissue was dihydrotestosterone from 5 min onwards, but only insignificant amounts of dihydrotestosterone were found in the culture medium during the first hour. Physiological concentrations of the synandrogens did not alter the metabolism of testosterone or the accumulation of the steroids into the tissue. Oestradiol, progesterone and unlabelled testosterone in a 500-fold concentration markedly reduced the conversion of tritiated testosterone to dihydrotestosterone while cyproterone and dihydrotestosterone had no effect. The possible role of other hormones in the alteration of testosterone metabolism in the target organs as the mechanism of synandrogenic or antiandrogenic action is discussed.


1991 ◽  
Vol 145 (1) ◽  
pp. 188-191 ◽  
Author(s):  
Yoshihiro Okuda ◽  
Masato Fujisawa ◽  
Osamu Matsumoto ◽  
Sadao Kamidono

Endocrinology ◽  
1999 ◽  
Vol 140 (10) ◽  
pp. 4509-4515 ◽  
Author(s):  
A. Stuart Wright ◽  
Robert C. Douglas ◽  
Lynn N. Thomas ◽  
Catherine B. Lazier ◽  
Roger S. Rittmaster

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.


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