Acid phosphatase (EC 3.1.3.2) activity was examined for its possible utilization as a biochemical marker for the profound changes that occur in the prostate gland after castration. Tissue filtrates were prepared from the prostate glands of mature male rats at various times after castration. The acid phosphatase activity was characterized by polyacrylamide gel electrophoresis and the percentage inhibition in the presence of tartrate. Prostatic acid phosphatase from mature rats has been shown to have two bands of activity, a lysosomal acid phosphatase and a secretory acid phosphatase. After castration, there was a loss of the secretory acid phosphatase from gel electrophoresis patterns by day 5 and a corresponding rise in the percentage inhibition by tartrate from the normal value of 43·2% to a maximum of 55·4% on day 7. Between days 7 and 15 there was a linear decrease in the percentage inhibition by tartrate, but after day 15 the value did not change significantly from 31·1% After castration, the specific activity of the uninhibited enzyme increased from a normal basal level of 2·16 μmol h−1 mg protein−1 to a maximum on day 7 of 8·10 μmol h−1 mg protein−1. After this time, the specific activity decreased slowly until it reached a normal level on day 21. Intraperitoneal administration of testosterone, 5α-dihydrotestosterone or 5α-androstane-3α,17β-diol at a dose of 2 mg/day and starting immediately after castration prevented the changes in percentage inhibition by tartrate and the loss of the secretory band of acid phosphatase. Administration of these androgens from day 7 after castration led to a decrease in the percentage inhibition from 50·1% to a minimum of 31·5% before the level returned to the normal value found in the mature rat. The secretory band of acid phosphatase, which was not present in gels at day 7, reappeared after 8–11 days of treatment with androgens. Of the androgens used,5α- androstane-3α,17β-diol was the most potent.

Androgen-independent cell lines have been clonally selected from primary cultures of androgen-dependent epithelial cells from the rat ventral prostate. These rapidly dividing epithelial-like cells (RDE) have altered morphology and adherence characteristics. Unlike normal prostate epithelial cells, the RDE cell lines do not require androgens for cell division or cell survival. In the presence of physiological concentrations of testosterone, the isoelectric focusing patterns of prostatic acid phosphatases are abnormal in these RDE cells, and the prostate steroid-binding protein genes are not expressed. The loss of androgen dependence is not due to the inability of RDE cells to metabolize testosterone to 5 alpha-dihydrotestosterone, the active androgen, since the RDE cell lines metabolize testosterone in a manner similar to normal androgen-dependent epithelial cells. When RDE cells are grown on collagen matrices, the cells assume ductlike structures, similar to prostatic acini, although PSBP gene expression is not induced. When seeded into soft agar these cell lines form distinct foci, suggesting that they are potentially tumorigenic.

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Certain characteristics of acid phosphatase in the adult male rat are under androgenic control. In further investigations of this control, (1) the polyacrylamide gel electrophoretic pattern of enzyme activity, (2) enzyme specific activity, and (3) the extent of inhibition of enzyme activity by 1-tartrate were examined for prostate, seminal vesicles, kidney, liver and testes from immature, maturing, young, and old mature adult rats. On gel electrophoresis, lysosomal acid phosphatase activity was found for all tissues from all groups of animals. Secretory enzyme was found for the prostate gland, but only after maturation (it appeared between days 28 and 35). At the same time the percent inhibition of activity by tartrate decreases. For the other tissues, the percent inhibition by tartrate increases for the liver and seminal vesicles but not for the kidney and testes. These changes may reflect alterations in lysosomal enzyme characteristics and can be related to known changes in androgen production throughout the life span of the rat.