Aromatase in hyperplasia and carcinoma of the human prostate

Abstract

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 [ 3 H] 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.

Benign prostatic hyperplasia (BPH) epithelial cell line BPH-1 induces aromatase expression in prostatic stromal cells via prostaglandin E2

“…Many studies have reported aromatase expression in the prostate by either RT-PCR or enzymatic activity using biochemical assays (Kaburagi et al 1987, Stone et al 1987, Matzkin & Soloway 1992, Tsugaya et al 1996, Negri-Cesi et al 1999. The level of E2 in stroma of BPH increases with age (Krieg et al 1993), and this increase was associated with an elevated expression of aromatase in prostatic stromal cells (PrSCs), especially those around hyperplastic glands in BPH patients (Hiramatsu et al 1997). We hypothesize that, in the prostate of elderly men, aromatase expression in PrSCs is induced by adjacent epithelial cells through secretion of a paracrine factor, leading to the increased production of estrogen.…”

“…Aromatase is the critical enzyme that converts testosterone into E2, and its expression was prominently high in PrSCs within hyperplastic glands in BPH patients (Hiramatsu et al 1997). Herein, we provided evidence to indicate that prostatic epithelial cells induced PrSCs to express aromatase through the secretion of PGE2.…”

Oestrogens and prostate cancer.

“…As there is increasing evidence that the prostate is a target for direct oestrogenic activity (Jarred et al 2000, Putz et al 2001, it is important to determine whether or not aromatase is expressed locally and to identify any changes that may occur with prostate disease. To date, aromatase expression in the prostate is contentious because the detection of enzymic activity or gene expression is equivocal; numerous reports have detected or failed to detect aromatase in prostatic tissue (Smith et al 1982, Kaburagi et al 1987, Stone et al 1987, Brodie et al 1989, Matzkin & Soloway 1992, Tsugaya et al 1996, Hiramatsu et al 1997, Negri-Cesi et al 1998, 1999. We believe that the discrepancies in the literature are partly due to the heterogeneity of prostatic tissue.…”

17β-hydroxysteroid dehydrogenase type 11 (Pan1b) expression in human prostate cancer

“…These locally produced androgens are also possibly metabolized and inactivated in human prostate cancer tissue. For example, aromatase was also reported to be expressed and in human prostate cancer tissue, possibly metabolizing testosterone into estrone (E1) [9]. In addition, AKR1C2, one of the human members of the aldo-keto reductase (AKR) 1C gene family, was reported to be expressed and convert DHT to 3α-diol in both human prostate cancer cell line and tissue [10,11].…”