Effect of a 4-methyl-4-aza steroid on androgen metabolism by rat ventral prostate epithelial and stromal cell cultures: Selective inhibition of 5α-reductase activity

The Prostate ◽  
1988 ◽  
Vol 13 (4) ◽  
pp. 289-297 ◽  
Author(s):  
John Orlowski ◽  
Albert F. Clark
Keyword(s):  
Cell Cultures ◽  
Stromal Cell ◽  
Reductase Activity ◽  
Selective Inhibition ◽  
Ventral Prostate ◽  
Androgen Metabolism ◽  
Rat Ventral Prostate

Androgen metabolism and actions in rat ventral prostate epithelial and stromal cell cultures

1986 ◽  
Vol 64 (6) ◽  
pp. 583-593 ◽  
Author(s):  
J. Orlowski ◽  
A. F. Clark
Keyword(s):  
Epithelial Cells ◽  
Cell Cultures ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cultured Cells ◽  
Cell Types ◽  
Ventral Prostate ◽  
Oxidoreductase Activity ◽  
Androgen Metabolism ◽  
Rat Ventral Prostate

The rat ventral prostate requires androgens for normal development, growth, and function. To investigate the relationship between androgen metabolism and its effects in the prostate and to examine differences between the epithelial and stromal cells, we have established a system of primary cell cultures of immature rat ventral prostate cells. Cultures of both cell types after reaching confluency (6–7 days) actively metabolized 3H-labelled testosterone (T), 5α-dihydrotestosterone (5α-DHT), 5α-androstane-3α,17β-diol, and 5α-androstane-3β,17β-diol. The epithelial cells actively reduced T to 5α-DHT and formed significant amounts of 5α-androstane-3,17-dione from T, 5α-DHT, and 5α-androstane-3α,17β-diol. All substrates were converted to significant amounts of C19O3metabolites. The stromal cells also metabolized all substrates, but very little 5α-androstane-3,17-dione was formed. The metabolism studies indicate that both cell types have Δ4-5α-reductase, 3α- and 3β-hydroxysteroid oxidoreductase and hydroxylase activities. The epithelial cells have significant 17β-hydroxysteroid oxidoreductase activity. The epithelial cells cultures grown in the presence of T have higher acid phosphatase (AP) contents (demonstrated histochemically and by biochemical assay). Tartrate inhibition studies indicate that the epithelial cells grown in the presence of T are making secretory AP. Stromal cell AP is not influenced by T. The results indicate that the cultured cells maintain differentiated prostatic functions: ability to metabolize androgens and, in the case of the epithelial cells, synthesize secretory AP.

THE ROLE OF THE STEROID-SENSITIVE CATION-DEPENDENT ATPASE IN HUMAN PROSTATIC TISSUE

1972 ◽  
Vol 54 (3) ◽  
pp. 375-385 ◽  
Author(s):  
W. E. FARNSWORTH
Keyword(s):  
Reductase Activity ◽  
Benign Prostatic Hypertrophy ◽  
Enzymic Activity ◽  
Ventral Prostate ◽  
Hormonal Stimulation ◽  
Dependent Atpase ◽  
Rat Ventral Prostate ◽  
Steroid Sensitive ◽  
Steroid Binding

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.

Androgen metabolism and regulation of rat ventral prostate growth and acid phosphatase during sexual maturation

1988 ◽  
Vol 116 (1) ◽  
pp. 81-90 ◽  
Author(s):  
J. Orlowski ◽  
C. E. Bird ◽  
A. F. Clark
Keyword(s):  
Acid Phosphatase ◽  
Sexual Maturation ◽  
Ventral Prostate ◽  
Secretory Function ◽  
Prostate Cell ◽  
Androgen Metabolism ◽  
Rat Ventral Prostate ◽  
Dna Contents ◽  
Weight Protein ◽  
Prostate Growth

ABSTRACT Androgen metabolism and the regulation of rat ventral prostate cell proliferation and secretory function were examined during sexual maturation. Changes in acid phosphatase (AP) characteristics were measured as a marker of androgen-dependent prostatic secretory function. In immature (21-day-old) rats, total AP activity per cell was low (14.2±1.3 mol p-nitrophenol phosphate hydrolysed/h per mg DNA); it increased threefold as the weight, protein and DNA contents of the prostate increased to adult (65-day) levels. This corresponded with significant (P<0.001) increases in the staining intensities of three of the four bands of secretory AP on isoelectric focusing gels. The extent of inhibition of AP by tartrate decreased at the same time. Secretory AP is known to be relatively tartrate-resistant. The changes in AP activity occurred after prostatic 5α-dihydrotestosterone (5α-DHT) levels increased from 4.6 ± 0.7 pmol/mg DNA (21 days) to reach a peak of 17.6±2.3 pmol/mg DNA at 58 days. Prostatic 5α-DHT concentrations were always higher than testosterone levels. Prostatic 5α-androstane-3α,17β-diol (3α-Adiol) levels were lower than 5α-DHT levels except on day 58 when levels peaked dramatically at 26.2±5.5 pmol/mg DNA. Changes in prostatic 5α-DHT and 3α-Adiol levels corresponded with changes in 5α-reductase and 3α-hydroxysteroid oxidoreductase (3α-HSOR) activities. The oxidative reaction of 3α-HSOR was approximately fourfold higher than the reductive reaction, indicating a preference for the formation of 5α-DHT. The plasma levels of testosterone, 5α-DHT and 3α-Adiol cannot account for their respective prostatic levels, indicating the importance of the steroid-metabolizing enzymes in regulating intracellular androgen levels. Changes in the AP characteristics could be correlated with the androgen status of the prostate. J. Endocr. (1988) 116,81-90

THE EFFECT OF OESTRADIOL-3N-BIS-(2-CHLOROETHYL)CARBAMATE-17β-PHOSPHATE (ESTRACYT®) ON THE 5α-REDUCTASE IN THE RAT VENTRAL PROSTATE

1975 ◽  
Vol 80 (1) ◽  
pp. 188-198 ◽  
Author(s):  
Per Aage Høisaeter
Keyword(s):  
Reductase Activity ◽  
Inhibitory Effect ◽  
Term Treatment ◽  
Significant Inhibition ◽  
Ventral Prostate ◽  
Rat Ventral Prostate ◽  
Long Term Treatment

ABSTRACT The ventral prostate of the rat both after in vitro incubation and in vivo experiments was found to contain appreciable 5α-reductase activity, whilst a very low activity was registered in the diaphragm and liver. Neither Estracyt® nor LEO275 (Estracyt® without the phosphate group in position 17 of the oestradiol moiety) had an inhibitory effect on the enzyme activity after in vitro incubation but equivalent amounts of oestradiol-17β and oestradiol-17β-phosphate significantly reduced 5α-reductase activity. When Estracyt® was injected in vivo no influence on activity was registered in "short term" experiments while a significant inhibition was found after "long term" treatment in vivo. Possible explanations for this "long term" effect of Estracyt® on 5α-reductase activity are discussed.

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