Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia

Abstract

Prostatic tissue removed at the time of cystoprostatectomy was separated into periurethral and peripheral zones. Homogenized tissue was incubated with [1,2,6,7³H] androstenedione in the presence or absence of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHAD) and a 5α-reductase inhibitor 4-MA (N,N-diethyl-4-methyl-3-oxo-4-aza-5α-androstane 17β-carboxamide). Estrogen formation was determined by reverse isotope dilution of [³H] estrone and [³H] estradiol and crystallization to constant specific activity. Control incubations were carried out in parallel utilizing heated prostatic tissue. Total estrogens produced in the periurethral zone in patients with benign prostatic hyperplasia (BPH) was 223 fmol/ mg protein/hr (SE ± 57) compared to 102 fmol (SE ± 17) in patients without BPH. Estrogen formation in the peripheral zone was 175 fmol (SE ± 69) and 105 fmol (SE ± 26) in patients with and without BPH, respectively. The prostatic aromatase exhibits Michaelis-Menton kinetics with an apparent Km of 90 nM. 4-OHAD inhibited aromatization in the prostatic tissue by 57-93%. Aromatization was also strongly inhibited by 4-MA, indicating that 4-MA is a potent aromatase as well as a 5α-reductase inhibitor in this tissue. These results suggest that aromatization of androgens to estrogens in the human prostate proceeds at a substantial rate and that local estrogen formation could preexist and be a factor in the etiology of BPH and prostatic cancer.