Aromatase in hyperplasia and carcinoma of the human prostate

Abstract

The expression and activity of aromatase was evaluated in 19 individuals with benign prostatic hyperplasia (BPH) and 26 prostatic carcinoma (PC) patients to elucidate the possible biological significance of in situ estrogen production in the development of human prostatic disorders. Marked aromatase immunoreactivity was observed in proliferative stromal cells, especially those around hyperplastic glands in 18 (95%) BPH patients and in stromal cells surrounding carcinomatous glands in 18 (69%) PC patient specimens. The percentage of aromatase‐positive stromal cells did not differ between BPH and PC. No significant correlation was apparent between the percentage of aromatase‐positive cells and either the extent of carcinoma differentiation or surgical stage in the PC patients. Quantitation of aromatase activity by the [3H] water assay yielded values of 27.23 ± 6.87 and 26.52 ± 9.12 fmol/hr/mg of protein for BPH (nine patients) and PC (nine patients), respectively. Reverse transcriptase and polymerase chain reaction analysis revealed that the mean aromatase mRNA content was 1.671 ± 0.82 and 1.11 ± 0.51 attomole/ng of total RNA (tRNA) for BPH (seven patients) and PC (four patients), respectively. There were no significant differences in aromatase activity or aromatase mRNA concentration between PC and BPH. The alternative use of multiple exons 1 of the aromatase gene was also examined. Predominant aromatase gene transcripts contained exon 1b in three of four of PC specimens and two of three BPH specimens examined, in contrast to the use of exon 1d previously described in normal prostate. Unlike breast and endometrium, therefore, aromatase expression in human prostate was not associated with malignancy. However, overexpression of aromatase, possibly attributable to abnormal gene regulation, may result in estrogen production in situ and play a role in the induction or development of human prostatic disorders. Prostate 31:118–124, 1997. © 1997 Wiley‐Liss, Inc.

Aromatase and regulating the estrogen:androgen ratio in the prostate gland

“…A number of studies successfully demonstrated aromatase expression in the prostate by RT-PCR as well as its enzymatic activity by biochemical assay [32][33][34][35][36][37]. In contrast, other studies failed to demonstrate the presence or activity of aromatase [38][39][40][41].…”

“…Much like the data examining aromatase in benign tissue, aromatase expression and activity in PCa and the PCa cell lines had been contentious for some time [32][33][34][35][36][37][38][39][40][41]. However, we demonstrated altered aromatase expression in PCa [42].…”

“…In contrast, other studies failed to demonstrate the presence or activity of aromatase [38][39][40][41]. Similarly, work examining the utilisation of the different aromatase promoters in prostate tissues also resulted in contradictory results [36,41].…”

Multidimensional approaches in dealing with prostate cancer

“…ERβ is involved in beneficial effects like anti-proliferation, differentiation and apoptosis. The ability of prostate gland to synthesize estrogens from a locally expressed enzyme aromatase adds to the complexity of the situation (Ellem et al, 2004;Hiramatsu et al, 1997). Aromatase plays a very important role in development of hormone dependent or related neoplasms as breast cancer (Simpson et al, 1994).…”

Pathophysiologie und Therapie der benignen Prostata-Hyperplasie

“…Zusammenfassend lässt sich sagen, dass diese Veränderungen auf eine erhöhte stromale DHTProduktion über eine verminderte Ratio von AKR1C1:AKR1C2 hinweisen, welche eine 3a-Diol Bildung bevorzugt (durchbrochene rote Linien). 3a-Diol wird anschließend über eine relativ hohe Ratio von RL-HSD:AKR1C2 zu DHT rückkonvertiert [ [44]. Dies hat zur Entwicklung und Anwendung von Anti-Ös-trogenen und besonders Aromataseinhibitoren zur Therapie der BPH/BPE und dem Prostatakarzinom geführt.…”