Cancer Res. 1989 Dec 1;49(23):6551-5.  

Erratum in:
    Cancer Res 1990 Jan 15;50(2):449.

Lack of evidence for aromatase in human prostatic tissues: effects of
4-hydroxyandrostenedione and other inhibitors on androgen metabolism.

Brodie AM, Son C, King DA, Meyer KM, Inkster SE.

Department of Pharmacology and Experimental Therapeutics, School of Medicine,
University of Maryland, Baltimore 21201.

The effects of 4-hydroxyandrostenedione (4-OHA) and other aromatase inhibitors,
10-propargylestr-4-ene-3,17-dione and
imidazo[1,5-alpha]-3,4,5,6-tetrahydropyrin-6-yl-(4-benzonitrile), as well as 5
alpha-reductase inhibitors N,N-diethyl-4-methyl-3-oxo-4-aza-5
alpha-androstane-17 beta-carboxyamide and
4-methyl-3-oxo-4-aza-androsta-5-ene-17-ol were investigated in prostatic tissue
from six patients with benign prostatic hypertrophy and seven patients with
prostatic cancer, and from normal men at autopsy. We attempted to measure
aromatase activity in the tissue incubations by quantitating 3H2O released from
androstenedione or testosterone labeled at the C-1 position. High performance
liquid chromatography and thin layer chromatography were used to isolate steroid
products. Although the amount of 3H2O released was at least twice that of the
heat-inactivated tissue samples, no estrone or estradiol was detected on high
performance liquid chromatography. The 3H2O release was significantly inhibited
by 4-OHA and N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17
beta-carboxyamide, but not by the other aromatase inhibitors. 4-OHA also
inhibited 5 alpha-reductase in both benign prostatic hypertrophy and cancer
tissue, although to a lesser extent than N,N-diethyl-4-methyl-3-oxo-4-aza-5
alpha-androstane-17 beta-carboxyamide. The other aromatase inhibitors were
without effect on 5 alpha-reductase. Our results indicate that 3H2O released
from [1 beta-3H]androstenedione and [1,2,6,7-3H]androstenedione does not
correlate with estrogen formation and may be the result of other metabolic
reactions. Although it appears that the prostate lacks aromatase, 4-OHA may be
of benefit in patients with benign prostatic hypertrophy or prostatic cancer by
inhibiting this enzyme in peripheral tissue.

PMID: 2479464 [PubMed - indexed for MEDLINE]