Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue

OBJECTIVE: To investigate the hormonal regulation of P450 aromatase activit y (responsible for the conversion of C19 androgens to C18 oestrogens) in hu man adipose tissue from men and pre- and post-menopausal women. SUBJECTS: Subcutaneous abdominal adipose tissue was obtained from 19 subjec ts: six pre-menopausal females (mean age 41.8 +/- (s.e.m.) 2.5; mean weight 76.01 +/- 5.6 kg), eight post-menopausal females (mean age 59.9 +/- 2.0; m ean weight 63.5 +/- 2.6 kg), and five males (mean age 35.8 +/- 8.8; mean we ight 78.5 +/- 7.8 kg) undergoing elective or cosmetic surgery. MEASUREMENTS: Cell viability and cell size were determined using staining t echniques. RT-PCR was used to confirm the presence of aromatase, The regula tion of aromatase activity was characterized using androstenedione as a sub strate in a tritiated water release assay. Aromatase activity was analysed in abdominal subcutaneous stromal cells (ASC) and mature adipocytes (AD) cu ltured in serum-free medium with cortisol (10(-6)-10(-7) M), insulin (500 n M) or a combination of both. RESULTS: In ASC aromatase activity increased in females from 14.5 +/- 1.7 t o 29.3 +/- 2.6 pmol/mg/h (n = 14, P < 0.05) and to 25.2 +/- 2.1 pmol/mg/h w ith cortisol (10(-7) M) and insulin, respectively (P<0.05). In males ASC ba sal aromatase activity (20.5 +/- 4.2 pmol/mg/h; n = 5) was inhibited by cor tisol (10(-7) M) alone (12.3 +/- 1.8 pmol/mg/h) and in combination with ins ulin (6.6 +/- 1.2 pmol/mg/h; men vs women, P < 0.005). Aromatase activity i n mature adipocytes was stimulated by cortisol plus insulin (P < 0.05) with no gender-specific differences. Treatment of ASC from both pre- and post-m enopausal females with cortisol alone (10(-6)M; 10(-7)M) or in combination with insulin demonstrated significantly different aromatase regulation comp ared with male aromatase stromal cell regulation (P < 0.05); however there were no differences in aromatase regulation between pre- and post-menopausa l females either in stromal cells or adipocytes. CONCLUSION: This study shows intrinsic gender differences in the regulation of aromatase, suggesting that differential enzyme regulation may affect se x steroid metabolism to alter the pattern of fat distribution between the s exes.