Benign Prostatic Hypertrophy Tissue Research Articles

Concentrations of androgens in human benign prostatic hypertrophic tissues incubated for up to three days

Twenty-one samples of surgically removed benign prostatic hypertrophy (BPH) were brought to the laboratory either in an insulated container (ambient temperature) or on ice. They were cleaned and roughly minced at room temperature. In 18 cases, samples of up to 1 g were kept at various temperatures (4 degrees C, c. 20 degrees C, and 37 degrees C) for up to 77 h; some were taken for storage (-70 degrees C) at the beginning and others at various times within this period. In three cases, portions of tissue were incubated in liquid medium in the absence and presence of testosterone. The concentrations of six androgens (testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), 5 alpha-androstane-3 alpha, 17 beta-diol, androstenedione, 5 alpha-androstanedione, and androsterone) were measured by radioimmunoassays. The results indicated that in conditions resembling those after death, the BPH tissue content of 5 alpha-DHT falls to a variable degree, while concentrations of 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstanedione, and androsterone increase. After 2 to 3 days, the 5 alpha-DHT concentrations remained greater than those reported previously from this laboratory (and others) in normal prostate tissue removed at autopsy.

Prostate Growth Factor in the Extracts of Benign Prostatic Hypertrophy

The biochemical and physicochemical properties of prostate growth factor (PGF) in the extracts of benign prostatic hypertrophy (BPH) were investigated. The PGF activity stimulating the proliferations of fibroblasts (mouse 3T3 and human BUD-8 cells) was detected predominantly in BPH prostate, and also in normal human prostates and well-differentiated adenocarcinoma prostates. No significant correlation between PGF contents and BPH tissue weight or histological differences (fibromuscular or glandular type) was detected. Gel filtration and isoelectric focusing indicated that partially purified factor(s) by ion exchange column chromatography had a multimolecular form comprising three active components (80,000, 43,000 and 10,000 daltons) and acidic isoelectric points (pH 4.0, 4.3, and 6.0). The activity was susceptible to heat treatment at 80 degrees C for 10 min, and to trypsin, but the factor was devoid of esteropeptidase activity. Subcellular fractionation located the entire activity in cytosol fraction.

Androgen receptors in bladder tumors

Cytosol androgen receptor content of transitional cell bladder cancer tissue was found to be substantially higher than its content in normal bladder mucosa and lower than in control benign prostatic hypertrophy tissue. Tumors arising in female patients had a lower androgen receptor content than those arising in male patients. High-grade tumors had a lower androgen receptor content than low-grade tumors.

Tamoxifen decreases human prostate CPK concentration

AbstractCreatine phosphokinase (CPK) was measured in whole prostate tissue of patients with benign prostatic hypertrophy (BPH) who were given Tamoxifen and/or megestrol acetate for seven days prior to transurethral resection of the prostate. Tamoxifen and Tamoxifen plus Megace®, but not Megace® alone, significantly decreased CPK concentrations in whole prostate tissue in comparison to untreated controls, suggesting that CPK is an estrogen‐dependent enzyme in the prostate. CPK concentration was also measured separately in mechanically separated prostate stroma and epithelium. The levels of CPK were 2.19 times higher in stroma than epithelium. This study suggests that CPK may be a marker for estrogen stimulation of the stroma in BPH tissue.

Interaction between prolactin and zinc in the human prostate gland.

The interaction between prolactin and zinc was examined in vitro in the human prostate gland. The results indicated that prolactin did not modulate the acute uptake of zinc into benign prostatic hypertrophy tissue whereas zinc, in contrast, increased the uptake of prolactin into the prostate gland. Our study further showed that the augmented uptake of prolactin by zinc was partly due to an increase in the non-specific binding properties of the peptide hormone. We were also able to demonstrate that the specific binding of 125I-labelled human prolactin to the receptor was reduced in the presence of zinc by a competitive mechanism.

The metabolism of androstenedione and testosterone to C 19 metabolites in normal breast, breast carcinoma and benign prostatic hypertrophy tissue

In previous studies from our laboratory of the metabolism of androstenedione (A) and testosterone (T) in breast adipose and breast carcinoma tissue, the aromatization of these compounds, and their interconversion were demonstrated. The present study describes the conversion of androstenedione and testosterone to C 19 metabolites in homogenates of normal breast tissue and breast carcinoma tissue and examines the C 19 metabolites in homogenates of benign prostatic hypertrophy (BPH) tissue under similar conditions. Tissue homogenates were incubated for 90 min in Krebs-Ringer bicarbonate buffer (pH 7.4) with ATP (3 mM) and NADPH (2.4 mM) as co-factors. Following extraction with ethyl acetate, the metabolites were separated into neutral and phenolic fractions. Identification of specific products was made by thin layer and paper chromatography and recrystallization procedures. The formation of C 19 metabolites was 10-fold greater in prostate than in breast tissue. Androsterone was the major product of androstenedione in both breast and prostate. The other 5α-metabolites of androstenedione identified were dihydrotestosterone (DHT) and epiandrosterone (EPI). The 5β-metabolite, etiocholanolone (ET10), was identified in both breast and prostate following incubation with androstenedione. Using testosterone as substrate, dihydrotestosterone was the major product in normal breast and BPH. Etiocholanolone was detected in breast, but not in prostate following incubation with testosterone. Aromatization was demonstrated in all incubations with breast tissue, but not in prostate. The results indicate that androstenedione is actively metabolized by both breast and prostate to 5α reduced metabolites. They also identify the formation of etiocholanolone in both tissues. Aromatization was demonstrated only in breast tissue.

Inhibin in the human prostate.

"Inhibin"-like protein, partially purified from the human prostate, was similar to that obtained from human seminal plasma under identical conditions. Concentration of inhibin in human prostate was tenfold higher as compared to human testis and was active biologically and immunologically. The presence of a high amount of inhibin in prostate seems to be unique in humans. Further inhibin concentration in benign prostatic hypertrophy tissue increased by tenfold in comparison to normal or cancerous tissue. Hence determination of serum level of inhibin may be used as a therapeutic tool to monitor prostate diseases.

Kinetics of 3H-testosterone and 3H-dihydrotestosterone metabolism in patients with benign prostatic hypertrophy. Effect of cyproterone acetate.

The response of 3H-testosterone and 3H-dihydrotestosterone to the administration of cyproterone acetate (CA) over a period of 5 days was investigated. Both tracers were injected intravenously in patients with benign prostatic hypertrophy. Blood was withdrawn for up to 5 h. Benign prostatic hypertrophy tissue was obtained by transurethral resection. Nine patients served as controls. Eleven patients received 300 mg CA intramuscularly. Cyproterone acetate suppressed testosterone and FSH, but not LH. 3H-testosterone was cleared more rapidly from plasma in the patients given CA presumably due to increased metabolism in the liver. 3H-dihydrotestosterone, however, remained virtually uninfluenced. Moreover, CA did not significantly alter the 3H-testosterone and 3H-dihydrotestosterone uptake and metabolism within prostatic tissue.

ANDROGEN LEVELS IN THE PLASMA AND PROSTATIC TISSUES OF PATIENTS WITH BENIGN HYPERTROPHY AND CARCINOMA OF THE PROSTATE

Specific radioimmunoassays for testosterone, dihydrotestosterone (DHT) and androstenedione were carried out to measure the concentrations of the three hormones in the plasma and prostatic tissue of ten patients with benign prostatic hypertrophy (BPH) and ten patients with carcinoma of the prostate. The results indicate that there are no significant differences between the peripheral plasma concentrations of testosterone, DHT and androstenedione in BPH [19.7 +/- 2.6, 2.6 +/- 0.9 AND 5.5 +/- 1.7 (S.E.M.) nmol/l respectively] and in carcinoma [16.9 +/- 2.8, 2.4 +/- 0.5, 4.4 +/- 1.1 nmol/l respectively], (in all cases P greater than 0.1). In contrast, the prostate tissue rations DHT: testosterone (3.59 +/- 0.55 for BPH and 0.66 +/- 0.09 for carcinoma) and androstenedione: testosterone (2.83 +/- 0.38 for BPH and 1.07 +/- 0.16 for carcinoma) are significantly less in carcinoma than in benign hypertrophy ( in all cases P less than 0.01). The accumulation of testosterone in the carcinoma, relative to values found in BPH tissue is, therefore, not associated with changes in the concentrations of androgens in the plasma pool but may be related to local factors and metabolic changes within the prostate.

Binding of [ 3H] methyltrienolone (R 1881) in rat prostate and human benign prostatic hypertrophy (BPH)

Methyl trienolone (R 1881 —17β-hydroxy-17α-methyl-estra-4, 9, 11-trien-3-one) binding to rat ventral prostate cytosol has a specificity typical of an androgen receptor. In human benign prostatic hypertrophy (BPH) tissue, the specificity of [ 3H] R 1881 binding is different from that measured in rat prostate: progesterone and R 5020 (17, 21-dimethyl-19-nor-4, 9-pregnadiene-3, 20-dione) being more potent while 19-nortestosterone is less potent competitor. Moreover, the synthetic progestin [ 3H] R 5020 binds to BPH tissue with a similar specificity. These data suggest the presence of progestin bindng components or of an atypical androgen receptor in human BPH cytosol.