2-methoxyestradiol, an endogenous metabolite of 17 beta-estradiol, inhibits adipocyte proliferation

The effects of 2-methoxyestradiol (2ME), a naturally occurring mammalian me tabolite of 17 beta-estradiol, on adipocyte growth has been investigated in mouse brown adipose tissue precursor cells developed in primary culture. 2 ME inhibits brown adipocyte proliferation in a dose-response manner (IC50 = 1.7 x 10(-6) M for DNA synthesis), with much higher potency than its hormo ne precursor 17 beta-estradiol, and cells acquire the typical differentiate d morphology - more round with a higher content of triglycerides. 2ME cause s similar effects in the immortal brown adipocyte tumor-derived hibernoma c ell line HIB 1B and the immortal 3T3-F442A white adipocyte line. These find ings suggest a possible role for 2ME in adipocyte proliferation, and probab ly in the differentiation process, entering the cells in the adipogenic pro gram.