Conversion of Androstenedione to Estrone in Human Fibroblasts Cultured from Prostate, Genital and Nongenital Skin[*]

Abstract

The conversion of (1,2,6,7-³H] androstenedione to [³H]estrone was measured in fibroblast monolayers grown from 3 prostates with benign prostatic hyperplasia (BPH), 3 prostates with prostatic carcinoma, 1 normal prostate of a 26 year old man and from foreskin and nongenital skin sites of 4 males. The reaction product estrone was purified by celite column followed by four successive thin layer chromatographies and final recrystallization to constant ³H/¹⁴C ratio.

Under the standardized conditions utilized estrone formation was linear with time from 1/2 hour up to 24 hours. The half maximum rate of estrone formation (km) was observed for both fibroblasts originating from BPH and prostatic carcinoma at about 0.1 µM, a value that is similar to that reported for human placental microsomes. In all cell strains examined estrone formation was found to be higher in foreskin than in nongenital skin, where estrogen formation in 3 out of 4 samples did not exceed more than twice the value of the blank and thus was considered to be zero. Estrone formation was highest in fibroblasts from BPH where values varied from 3.0 to 11.6 pmol/100 mg protein/ hour incubation. The corresponding values measured in fibroblasts from prostatic carcinoma were clearly lower, ranging from 0.8 to 2.0 pmol/100 mg protein/hour incubation.

In fibroblasts grown from the normal prostate of a 26 year old man, estrone formation was similar to that observed with fibroblasts from prostatic carcinoma.

Since it is well documented that estrogen can exert profound effects, both directly and indirectly, on prostatic growth and function and recent work shows that estrogen can act synergistically with biologically active derivates of testosterone to induce BPH, the demonstration of high estrone formation in fibroblasts from BPH might be important as to the pathogenesis of this disorder. The low estrogen formation as observed in fibroblasts grown from prostatic carcinoma is unclear at present.

It might be conceivable that a low intracellular estrogen formation in the prostate favors carcinomatous growth.

Key words

Estrone Formation - Cultured Fibroblasts - Benign Prostatic Hyperplasia - Prostatic Carcinoma - Foreskin

1 European Prize Essay Paper of the German Endocrine Society; Schoeller-Junkmann Award 1979

1 European Prize Essay Paper of the German Endocrine Society; Schoeller-Junkmann Award 1979