Circulating androstenedione is converted to estrone in adipose tissue, which is the principal site of estrogen biosynthesis in postmenopausal women. This reaction is catalyzed by a specific form of cytochrome P450 (P450arom; the product of the CYP19 gene). The fractional conversion of plasma androstenedione to estrone as well as the specific activity of aromatase in adipose stromal cells were previously shown to increase with advancing age. To determine whether this positive effect of aging on estrogen biosynthesis is due to an alteration in tissue levels of P450arom transcripts, we quantified P450arom mRNA levels in sc fat biopsy samples (n = 33) from buttocks, thighs, and abdomen of 11 women who ranged in age from 23-61 yr. Competitive polymerase chain reaction linked to reverse transcription was used to quantify P450arom transcripts in total RNA that was isolated from sc fat obtained by needle aspiration. In each sample, primer extension and coamplification of a rat P450arom cRNA as an internal standard were used to control possible differences in amplification efficiencies between samples. The results demonstrate that with advancing age in women, there is a progressive and statistically significant increase in adipose tissue P450arom transcript levels (normalized to total RNA content) in buttocks, thighs, and abdomen (correlation coefficients: r = 0.704, 0.854, and 0.933, respectively). The levels of transcripts observed in the older subjects reach 2- to 4-fold greater than those observed in the young women. Adipose tissue P450arom transcript levels were highest in the buttocks, followed by the thighs, and lowest in the abdomen. This increase in P450arom transcript levels is likely to be a major factor contributing to the increased extragonadal estrogen biosynthesis in elderly women.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical