Tissue dihydrotestosterone and 5alpha-reductase (delta4-3-ketosteroid-5alpha-oxidoreductase) levels have been measured in prostates of patients with cancer and benign prostatic hypertrophy; significant decreases in average values for both of these biochemical parameters were noted in prostate cancer compared to benign prostatic hypertrophy, although individual values overlapped in both groups. Prostate cancer tissue dihydrotestosterone levels appeared to correlate better than did either histological tumor grading or 5alpha-reductase with the ultimate clinical response to antiandrogen therapy. These results suggest that assay of tissue dihydrotestosterone levels in prostate cancer should be further explored as a possible marker for tumor differentiation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1977

Rapid purification of an RNA tumor virus and proteins by high-performance steric exclusion chromatography on porous glass bead columns.

High-performance steric exclusion chromatography on a 1250-A pore size polyethylene glycol-treated glass bead column was used to purify avian myeloblastosis virus and hamster melanoma virus from plasma protein and tissue culture media. The purified hamster melanoma virus was still infectious and the avian myeloblastosis virus-associated RNA-directed DNA polymerase showed a 1100-fold purification of the virus from one column treatment. Electron microscopy of the purified virus showed intact particles, with surface projections evident. The time required for column purification of the virus was 5 min.

Alkaline Phosphatase↗

PubMed1977

Intestinal perfusion studies in tropical sprue. 2. Movement of water and electrolytes.

Jejunal absorption of sodium and water has been investigated in 10 normal Indians and 11 patients with chronic tropical sprue. Normal saline and solutions containing amino acids and dipeptides were studied. In both groups little absorption of sodium and water from normal saline was seen. Mean water and sodium absorption from the free amino acid or dipeptide solutions showed no significant difference between the groups and was similar to absorption from normal saline. These results differ from data obtained in normal English subjects where at these concentrations significant stimulation of sodium and water absorption was seen. In a proportion of subjects in both groups net secretion was observed. However, no correlation was seen between mucosal histology or luminal bacteriology and sodium or water movement. These findings in patients with chronic tropical sprue are similar to findings in normal Indians and suggest that jejunal handling of sodium and water is abnormal when compared with normal English subjects, but that the mucosa is not in a secretory phase as seen in certain other diarrhoeal states or in the acute early phase of sprue.

Amino Acids↗

PubMed1977

Using antiandrogen therapy in benign prostatic hypertrophy.

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Aged↗

PubMed1976

A method for tissue extraction and determination of prostate concentrations of endogenous androgens by radioimmunoassay.

A method for simultaneously determining concentrations of major androgens in prostate has been developed. Extraction techniques used to isolate the androgens from minced tissue include homogenization with high-speed blades in Delsal's solvent mixture, adsorption to silica gel, followed by column and one thin-layer chromatography (TLC). Radioimmunoassays (RIA) of small aliquots of TLC eluates are used to quantitate picogram amounts of 5alpha-dihydrotestosterone (DHT) and 5alpha-androstanediols (Diol) and to estimate testosterone (T) and androstenedione (Ad). Contamination of blanks was reduced to RIA sensitivity limits primarily by treatment of glassware in a self-cleaning oven. The specificity of the method for each androgen was established by TLC separations of known prostate metabolites, antisera specificities, and parallelism of sample aliquots to androgen RIA standards. The overall precision, in terms of coefficients of variation, was 21% for DHT and 24% for Diol. T and Ad could not be measured with acceptable precision because their very low concentrations in prostate (less than or equal 0.5 ng/g tissue) were less than RIA sensitivity limits. Accuracy studies indicated recoveries ranging from 96% for Diol to 121% for DHT. In human benign hypertrophic prostate tissue, DHT averaged 153 ng/g soluble protein (5.8 ng/g tissue) which was 17 times higher than values obtained in human spleen and kidney; Diol in prostate showed no consistent differences from values noted in kidney or spleen.

Androgens↗

PubMed1976

Prostate concentrations of endogenous androgens by radioimmunoassay.

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Androgens↗

PubMed1976

Comparison of androgen metabolites in benign prostatic hypertrophy (BPH) and normal prostate.

5 alpha-Dihydrotestosterone (DHT) and androstanediols (diols) have been measured in human prostate tissue. DHT levels in surgical specimens of prostate from 8 patients with BPH averaged 5.6 +/- 0.93 S.E. ng/g and were significantly greater than (P less than 0.01) values of 2.1 +/- 0.32 S.E. ng/g in 6 normal prostates obtained post-mortem from males less than 50 yrs old. Androstanediols averaged 2.3 +/- 0.35 S.E. ng/g in the BPH specimens compared to values of 10.2 +/- 2.4 S.E. ng/g in the normal prostates (P less than 0.01). This significantly higher (P less than 0.001) ratio of diols/DHT in the normal (5.1 +/- 0.93 S.E.) compared to the BPH prostate (0.45 +/- 0.08 S.E.) suggests that a decrease in 3-hydroxysteroid oxido-reductase, which converts DHT to diol, may be an important clue to the pathogenesis of BPH.

Androstane-3,17-diol↗

PubMed1976

Effect of megestrol acetate (Megace) on steroid metabolism and steroid-protein binding in the human prostate.

Megestrol acetate (Megace), an antiandrogen, was administered in a dosage of 80 mg daily to 6 patients with benign prostatic hypertrophy (BPH) for 4 to 25 days prior to transurethral resection of the prostate (TURP). Surgical tissue from drug-treated patients was compared to untreated controls in regard to: 1) the enzymatic reduction of testosterone (T) and dihydrotestosterone (DHT); 2) DHT binding to a cytosol receptor protein; 3) tissue levels of endogenous dihydrotestosterone and androstanediols (diols). When minced prostate was incubated with 3H-T and 14C-androstenedione for 1 h at 37 C, prostate 5alpha-reductase activity, measured as reduced products formed from substrate, decreased to 31% and 39%, respectively, of the control values. Prostate 3-oxido-reductase enzyme activity, measured as diols formed from 3H-DHT, was decreased to neglible values in Megace-treated patients compared to an 8.7% conversion to diols in controls. No 3H-DHT binding to a cytosol receptor protein could be demonstrated in 4 out of 5 prostates from Megace-treated patients, whereas the presence of such a receptor was noted in 14 out of 17 untreated controls. Endogenous DHT levels in Megace-treated patients averaged 1.1 ng/g (SE = 0.26), significantly less than the average of 3.9 ng/g (SE = 0.49) found in controls (P less than 0.001). No significant difference was noted in endogenous diols. In addition to these effects on tissue, Megace significantly decreased plasma levels of T, LH, and FSH at the end of the 4- to 25-day period; plasma prolactin levels did not change. Continued studies of Megace for the possible treatment of benign prostatic hypertrophy may be warranted since the drug appears to block several important biochemical steps which mediate the effects of androgen on the human prostate.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗