CHARACTERISTICS OF THE NUCLEAR AND MICROSOMAL STEROID Δ4-5α-HYDROGENASE OF THE RAT PROSTATE

1974 ◽  
Vol 76 (3) ◽  
pp. 608-624 ◽  
Author(s):  
Kaoru Nozu ◽  
Bun-ichi Tamaoki
Keyword(s):  
Carboxylic Acid ◽  
Potent Inhibitor ◽  
Enzymatic Properties ◽  
Ventral Prostate ◽  
Microsomal Enzymes ◽  
Rat Ventral Prostate ◽  
Conversion Rates ◽  
Optimum Ph ◽  
Rat Prostate

ABSTRACT Steroid Δ4-5α-hydrogenase was intracellularly localized in the nuclear and microsomal fractions of the rat ventral prostate (Nozu Sc Tamaoki 1973). The nuclear Δ4-5α-hydrogenase was found to have the following enzymatic properties essentially similar to the microsomal Δ4-5α-hydrogenase, with regard to the metabolism of [4-14C] testosterone in the presence of NADPH: The optimum pH of the enzymes in the two fractions was around 7.0 and the maximal conversion rates were obtained at a temperature of 35 to 40°C. The apparent Km values of the nuclear and microsomal Δ4-5α-hydrogenases were estimated respectively as 1.05 and 0.90 μmol/l, while the Km value of the hepatic microsomal Δ4-5α-hydrogenase was simultaneously estimated as 154 μmol/l. Among steroids, the most potent inhibitor group on the enzymatic 5α-hydrogenation of testosterone was Δ 4-3-oxo-C-21 steroids such as progesterone and 17α-hydroxyprogesterone, which were competitively converted into their 5α-hydrogenated metabolites in the highest rates. Among some anti-androgens, cyproterone and its acetate hardly inhibited the activities of the nuclear and microsomal enzymes, whereas etienic acid (4-androsten-3-one-17β-carboxylic acid), oestradiol-17β and diethylstilboestrol markedly inhibited both prostatic enzymes in a competitive manner. The Ki values of etienic acid, oestradiol-17β and diethylstilboestrol for the nuclear Δ4-5α-hydrogenase were respectively 1.50, 0.49 and 1.02 μmol/l, indicating similar affinities of these for the nuclear enzyme to that of testosterone.

scholarly journals Specific inhibition of the enzymic decarboxylation of S-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances

1974 ◽  
Vol 139 (2) ◽  
pp. 351-357 ◽  
Author(s):  
A. Corti ◽  
C. Dave ◽  
H. G. Williams-Ashman ◽  
E. Mihich ◽  
Amelia Schenone
Keyword(s):  
Potent Inhibitor ◽  
Aliphatic Amines ◽  
Ventral Prostate ◽  
Specific Inhibition ◽  
Adenosylmethionine Decarboxylase ◽  
Related Substances ◽  
Rat Ventral Prostate ◽  
Mammalian Tissues ◽  
Rat Prostate

Methylglyoxal bis(guanylhydrazone) {1,1′-[(methylethanediylidene)-dinitrilo]diguanidine} is a very potent inhibitor of putrescine-activated S-adenosylmethionine decarboxylases from many different mammalian tissues, including sublines of mouse L1210 leukaemia that are resistant to the drug as well as sublines that are sensitive. The inhibition of purified rat ventral prostate S-adenosylmethionine decarboxylase is competitive with respect to the S-adenosylmethionine substrate, and is much greater in the presence than in the absence of the activator putrescine. Inhibition by the drug depends, among other things, on the nature of the aliphatic amines that can serve as stimulators of rat prostate S-adenosylmethionine decarboxylase. Effects of some congeners of methylglyoxal bis(guanylhydrazone) on the enzyme are described.

The cellular mechanism of the antiandrogenic action of nomegestrol acetate, a new 19-nor progestagen, on the rat prostate

1987 ◽  
Vol 115 (4) ◽  
pp. 544-550 ◽  
Author(s):  
Jacqueline Botella ◽  
Jacques Paris ◽  
Brahim Lahlou
Keyword(s):  
Androgen Receptor ◽  
Cyproterone Acetate ◽  
Megestrol Acetate ◽  
Ventral Prostate ◽  
Chlormadinone Acetate ◽  
Rat Ventral Prostate ◽  
Nomegestrol Acetate ◽  
Nuclear Location ◽  
Rat Prostate

Abstract. Nomegestrol acetate, like other synthetic progestins such as medroxyprogesterone acetate (MPA), chlormadinone acetate, megestrol acetate and cyproterone acetate, is able to modify the physiological actions of androgens. In the present study, the effects of nomegestrol acetate and other antiandrogens on the binding of androgen to the androgen receptor (AR) and on the 'activation' of this receptor were investigated, using rat ventral prostate as target model. Relative binding affinities (RBA) for AR were first estimated in vitro with respect to [3H]testosterone for a series of structurally-related compounds. The values obtained ranged as follows: dihydrotestosterone (DHT) » megestrol acetate ≥ testosterone (T) > nomegestrol acetate > 19-nor progesterone (19NP) > progesterone (P). An assay was established, using two different incubation times (3 h and 24 h) to further investigate relationships between binding affinity and androgenic, or antiandrogenic, activity. The following order (as %) was obtained for progestins as against [3H]mibolerone (DMNT): 1) DMNT (100) » acetate (42) > megestrol acetate (29) > chlormadinone acetate (9) > MPA (8) > cyproterone acetate (6) after 3 h and 2) DMNT (100) » MPA (53) » nomegestrol acetate (19) > megestrol acetate (12) > chlormadinone acetate (14) and cyproterone acetate (8) after 24 h. Since the RBA of nomegestrol acetate declined with time, these results indicate that this substance may act like an antiandrogen rather than an androgen, while the contrary prevails concerning MPA. The effects of these progestins, administered either alone or in combination with DHT to the animals, on the location (nuclear or cytosolic) of AR were also analyzed. DHT (0.05 or 4 mg/kg) produced maximal nuclear location of AR. Of the progestins tested, only MPA and norethisterone acetate reproduced this effect, while other steroids were ineffective. Furthermore, cyproterone acetate, megestrol acetate and nomegestrol acetate were able to inhibit to a large extent the DHT-elicited effect. The evidence from these studies suggests that the new compound nomegestrol acetate may oppose the actions of androgens on ventral prostate by directly interacting with the androgen receptor.

THE EFFECT OF TESTOSTERONE AND TESTOSTERONE METABOLITES ON THE FINE STRUCTURE OF THE RAT PROSTATE GLAND IN ORGAN CULTURE

1972 ◽  
Vol 52 (3) ◽  
pp. 459-NP ◽  
Author(s):  
J. W. GITTINGER ◽  
ILSE LASNITZKI
Keyword(s):  
Fine Structure ◽  
Organ Culture ◽  
Prostate Gland ◽  
Golgi Body ◽  
Ventral Prostate ◽  
Normal Organ ◽  
Rat Ventral Prostate ◽  
Membrane Bound ◽  
Rat Prostate ◽  
Testosterone Metabolites

SUMMARY The action of testosterone and its metabolites, dihydrotestosterone and 3β-androstanediol on the fine structure of the rat ventral prostate gland in organ culture was investigated. In intact glands before explantation the epithelial cytoplasm showed a system of membrane-bound ergastoplasmic channels studded with ribosomes, a discrete Golgi body, associated with secretory vacuoles and microvilli projecting into the lumen. In explants grown in non-supplemented medium the epithelium underwent a severe regression. The ergastoplasm collapsed and was fragmented and there was no discrete Golgi body. Microvilli were absent and a number of electron-dense bodies interpreted as lysosomes were scattered throughout the cytoplasm. In explants grown in the presence of testosterone, dihydrotestosterone and 3β-androstanediol the fine structure was similar to that in the intact gland. Ergastoplasm and Golgi apparatus were well maintained, secretory vacuoles could be observed and the microvilli resembled in size and number those of the normal organ. In hyperplastic areas of explants treated with dihydrotestosterone, the maintenance of the ergastoplasm was less complete but the Golgi zone and microvilli were well preserved. In explants treated with testosterone or dihydrotestosterone, nucleolar bodies were observed in many nuclei of epithelium and stroma. The effects of the steroids on the fine structure of the gland confirm those seen at the light microscopic level and support the suggestion that the action of testosterone is mediated through its metabolites.

Regional and cellular distribution within the rat prostate of two mRNA species undergoing opposite regulation by androgens

1992 ◽  
Vol 132 (3) ◽  
pp. 361-NP ◽  
Author(s):  
S. Bettuzzi ◽  
M. Zoli ◽  
F. Ferraguti ◽  
M. C. Ingletti ◽  
L. F. Agnati ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Types ◽  
High Rate ◽  
Ventral Prostate ◽  
Photographic Emulsion ◽  
Cell Multiplication ◽  
Rat Ventral Prostate ◽  
A Cell ◽  
Rat Prostate ◽  
Different Cell Types

ABSTRACT We have investigated, by in-situ hybridization histochemistry, the distribution within the rat ventral prostate of the mRNAs for sulphated glycoprotein-2 (SGP-2) and ornithine decarboxylase (ODC; EC 4.1.1.17), two proteins that appear to be inversely regulated by androgens in this organ, in that the level of SGP-2 mRNA is lowered, while the activity of ODC is enhanced by the latter hormones. Low-magnification autoradiograms of whole ventral prostate sections showed that, in intact animals, the SGP-2 transcript was only detectable in restricted areas and not diffused evenly throughout the section. Reciprocally, the ODC transcript was not detectable in areas where the SGP-2 transcript was detected, but appeared distributed uniformly in the remaining parts of the section. The effect of castration on the levels of the two mRNAs was evaluated by a semiquantitative analysis of autoradiograms from whole ventral prostate sections using an autoimmune image analyser. Four days after castration, SGP-2 mRNA increased by about 11-fold, while ODC mRNA decreased by fivefold. The distribution of the two mRNAs among the different cell types, studied by treating the slides with photographic emulsion and counterstaining, showed that both were expressed exclusively in the epithelial luminal cells of the ducts. Furthermore, each of the two mRNAs preferentially accumulated in a cell population which was morphologically distinct while accumulation of the other was negligible. SGP-2 mRNA was mostly found in cuboidal epithelial cells and ODC mRNA in columnar epithelial cells. Castration caused a dramatic accumulation of SGP-2 and a decrease in ODC mRNAs in the cells of the columnar epithelium 4 days later. These data suggest that, in the ventral prostate of intact animals, SGP-2 is expressed in the proximal ducts whose luminal epithelium consists of cuboidal cells undergoing apoptotic phenomena and not in the intermediate and distal ducts characterized by columnar epithelia with active protein synthesis and cell multiplication. In the intermediate and distal parts of the ductal system the ODC gene would be expressed at a high rate while being turned off in the proximal ducts. Castration, resulting in apoptosis of the epithelial cells of the intermediate and distal ducts, caused SGP-2 to be actively expressed and ODC to be repressed in the latter segments. Journal of Endocrinology (1992) 132, 361–367

scholarly journals Immunohistochemical localization of rK9, an enzyme of the kallikrein gene family, in the rat ventral prostate.

1995 ◽  
Vol 43 (1) ◽  
pp. 61-65 ◽  
Author(s):  
T Berg ◽  
H Schøyen
Keyword(s):  
Immunohistochemical Localization ◽  
Immunofluorescent Staining ◽  
Ventral Prostate ◽  
Staining Reaction ◽  
Specific Staining ◽  
Rat Ventral Prostate ◽  
Indirect Immunofluorescence Technique ◽  
Rat Prostate ◽  
Related Proteins ◽  
Rat Submandibular Gland

The rat kallikrein family consists of multiple closely related proteins. Most of these proteins have been purified from rat submandibular gland (SMG), among them rK9, an enzyme that has a direct vasoconstrictory effect on isolated aortic rings. Recently, two members of the kallikrein family, rK8 and rK9, were also purified from rat prostate, whereas other family members were not detected in this organ. In the present study, the immunohistochemical localization of rK9 was determined in rat prostate by the indirect immunofluorescence technique with polyclonal antisera against rat SMG rK9 in the first layer. The crossreactivity pattern of the antiserum against rat prostate tissue extract was established by flat-bed isoelectrofocusing and immunoblotting. The antiserum reacted with prostate rK9 but not with prostate rK8. Specificity of the immunofluorescent staining reaction was verified by staining with the primary antiserum after addition of purified SMG or prostate rK9, or other members of the kallikrein family including prostate rK8. rK9-specific immunofluorescence was detected in the prostate ductal structures. In the distal (acinar) segments, rK9 was found in the cytoplasm as granular staining in the middle third of the cell, in the luminal cell wall, and in the secretion within the lumen. In the intermediate segments, strong rK9-specific staining was observed adhering to the luminal wall as well as abundantly within the ductal lumen.

Characterization and cloning of androgen-repressed mRNAs from rat ventral prostate

1987 ◽  
Vol 147 (1) ◽  
pp. 196-203 ◽  
Author(s):  
Jocelyne G. Léger ◽  
Michael L. Montpetit ◽  
Martin P. Tenniswood
Keyword(s):  
Ventral Prostate ◽  
Rat Ventral Prostate

FURTHER STUDIES ON A SOLUBLE ANDROGEN-MACROMOLECULAR COMPLEX FROM THE RAT VENTRAL PROSTATE

1970 ◽  
Vol 65 (3) ◽  
pp. 517-524 ◽  
Author(s):  
Olav Unhjem
Keyword(s):  
Hydrogen Atom ◽  
Keto Group ◽  
Ventral Prostate ◽  
Metabolic Inhibitors ◽  
Macromolecular Complex ◽  
Structural Requirements ◽  
Macromolecular Complexes ◽  
Rat Ventral Prostate

ABSTRACT The ability of various steroids and metabolic inhibitors to influence the binding of androgen to soluble macromolecules in the rat ventral prostate was evaluated in vitro. The results obtained revealed some structural requirements of steroids for binding to the macromolecules. An androstane skeleton with the α-configuration of the hydrogen atom at position 5 seemed to be essential for binding as well as a keto group at position 3. N-ethylmaleimide, Na-iodoacetate and p-hydroxymercuribenzoate inhibited the binding of androgen to macromolecules. The androgen-macromolecular complexes appeared to be rather stable at temperatures below 5°C.

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