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

scholarly journals Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia

2004 ◽  
pp. 591-603 ◽  
Author(s):  
C Crescioli ◽  
P Ferruzzi ◽  
A Caporali ◽  
M Scaltriti ◽  
S Bettuzzi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Phase Ii ◽  
Benign Prostate Hyperplasia ◽  
Ventral Prostate ◽  
Double Blind ◽  
Prostate Hyperplasia ◽  
Prostate Cell ◽  
Prostate Growth ◽  
Benign Prostate

OBJECTIVE: Calcitriol analogues might represent an interesting new therapy for benign prostate hyperplasia (BPH). We here report the preclinical characterization of BXL-628, an analogue selected for an ongoing double-blind, randomized, placebo-controlled phase II trial in BPH. DESIGN: Experiments with BXL-628 were carried out in human BPH cells and in the ventral prostate of intact and castrated rats. METHODS: BPH cell and rat prostate growth were evaluated along with morphological and biochemical hallmarks of apoptosis. RESULTS: BXL-628 inhibited human BPH cell proliferation and induced apoptosis even in the presence of androgens or growth factors. It also decreased prostate growth to an extent similar to finasteride, inducing DNA fragmentation and apoptosis, both in intact and in testosterone-supplemented castrated rats. Accordingly, BXL-628, like finasteride, increased the expression of clusterin, a prostatic atrophy marker. However, BXL-628 did not inhibit 5 alpha-reductase 1 and 2, did not bind to the androgen receptor (AR) in BPH homogenates and did not affect AR-coupled luciferase activity. In addition, BXL-628 did not affect rat pituitary and testis activity or calcemia. CONCLUSIONS: BXL-628 inhibited in vitro and in vivo prostate cell proliferation, and therefore might represent a novel, interesting option for the treatment of BPH.

scholarly journals ESTABLISHMENT AND CHARACTERIZATION OF A RAT VENTRAL PROSTATE CELL LINE DPE

1981 ◽  
Vol 31 (6) ◽  
pp. 481-489
Author(s):  
YOSHIKAZU ITO ◽  
KOICHI KITAURA ◽  
EIKO INOUE ◽  
YOICHI NAKAZATO
Keyword(s):  
Cell Line ◽  
Ventral Prostate ◽  
Prostate Cell ◽  
Prostate Cell Line ◽  
Rat Ventral Prostate

Immunofluorescent localization of an androgen-dependent isoenzyme of prostatic acid phosphatase in rat ventral prostate

1985 ◽  
Vol 213 (2) ◽  
pp. 131-139 ◽  
Author(s):  
Louis Terracio ◽  
Allyn Rule ◽  
John Salvato ◽  
William H. J. Douglas
Keyword(s):  
Acid Phosphatase ◽  
Prostatic Acid Phosphatase ◽  
Ventral Prostate ◽  
Immunofluorescent Localization ◽  
Rat Ventral Prostate

Impact of gestational diabetes and lactational insulin replacement on structure and secretory function of offspring rat ventral prostate

2014 ◽  
Vol 206 ◽  
pp. 60-71 ◽  
Author(s):  
Sérgio A.A. Santos ◽  
Jaqueline C. Rinaldi ◽  
Amanda E. Martins ◽  
Ana C.L. Camargo ◽  
Carina Leonelli ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Ventral Prostate ◽  
Secretory Function ◽  
Rat Ventral Prostate ◽  
Insulin Replacement

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.

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