Distribution of aromatase P450 transcripts and adipose fibroblasts in the human breast

The fibroblast component of adipose tissue is the primary extraglandular site of aromatase P450 (P450arom) expression, which is responsible for the conversion of C19 steroids to estrogens. Previously, we have shown positive correlations between the level of P450arom transcripts and the ratio of fibroblasts to mature adipocytes in adipose tissue samples proximal to breast tumors. The present study was conducted to determine the distribution of P450arom messenger ribonucleic acid (RNA) levels and fibroblast to adipocyte ratios in disease-free breasts of premenopausal women. Adipose tissue samples were collected from 3 regions (outer, upper, and inner) of both breasts of 13 women undergoing reduction mammoplasty. The histological composition of adipose tissue (n = 12) was determined by morphometry using a computerized image analysis program. We used a competitive RT-PCR method employing rat P450arom complementary RNA as an internal standard to quantify adipose P450arom transcripts in tissue total RNA samples (n = 11). Overall, 67% of the highest fibroblast to adipocyte ratios and 64% of the highest P450arom transcript levels were detected in an outer breast region, whereas in only 1 patient were the highest values detected in an inner region. Parametric ANOVA showed significant differences between the fibroblast content of the regions [p(F) = 0.037]. This distribution pattern directly correlates with the most common or the least common sites of carcinoma in the breast, the outer and inner regions, respectively. Moreover, a direct relationship was demonstrated between adipose fibroblasts and P450arom transcripts within the breast, in that regions with the highest fibroblast to adipocyte ratios contained the highest P450arom transcript levels (by ANOVA of contrast variables, P = 0.0009). These results suggest that, similar to our previous findings in the breast bearing a tumor, adipose tissue aromatase expression in the disease-free breast is determined by the local ratio of fibroblasts to adipocytes.