The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: influence of gender and site.

The gender-specific differences in body fat distribution suggest that sex steroids play an important role in regulating body fat distribution. Sex steroids may regulate adipose tissue mass by altering adipocyte number and size. The effects of various sex steroids on in vitro proliferation of preadipocytes from both sc and omental fat depots was investigated in men and women. Abdominal sc and omental preadipocytes from men (n = 14) and women (8 premenopausal and 7 postmenopausal) were cultured in the presence of 17beta-E2 (10(-7)-10(-9) M), estrone (10(-7)-10(-9) M), or dehydrotestosterone (DHT) (10(-7)-10(-9) M), and the rate of proliferation was measured over time (1-96 h) by DNA accumulation assays (micromoles per microg) and [(3)H]thymidine incorporation (disintegrations per min). In sc preadipocytes the rate of proliferation was increased between 24-48 h with E2 (10(-7) M) in both men (P = 0.028) and women (P = 0.017). Subcutaneous preadipocytes from women were more responsive to E2 in stimulating proliferation than those from men (women vs. men, DNA assay, 24 h, P = 0.014). In omental preadipocytes the increase in the rate of proliferation occurred at 24 h with E2 (10(-7) M) in women (P = 0.034) and at 48 h in men (P = 0.031). Gender appeared to influence the rate of proliferation by E2 in omental preadipocytes, with maximal stimulation of proliferation at 48 h in preadipocytes from women treated with E2 (10(-7) M; p = 0.007) compared with 72 h in preadipocyte cells from men (P = 0.048), as shown by DNA assay. Both estrone and the androgen DHT had no significant gender- or site-specific effect on the rate of proliferation at any time point. All DNA content data were further validated by thymidine incorporation analysis. In summary, E2 stimulates the rate of proliferation of preadipocytes in a dose-dependent manner, with significant gender- and site-specific differences. Neither estrone nor DHT affected adipocyte mass through proliferation of preadipocytes in this study. In conclusion, E2 may act as an important local factor influencing the proliferation of preadipocytes that may affect fat cell number in a depot- and gender-specific pattern in human abdominal sc and omental adipose tissue.