Effects of in vivo estrogen treatment on adipose tissue metabolism and nuclear estrogen receptor binding in isolated rat adipocytes

We have previously demonstrated the existence of nuclear estrogen receptors in isolated adipocytes (Pedersen et al. (1991) Biochim. Biophys. Acta 1093, 80-86). In the present study we have investigated the regulatory properties of these nuclear estrogen receptors, in addition to the metabolic effects of estrogen on adipose tissue metabolism. Estrogen treatment (20 μg 17β-estradiol in NaCl for 7 days) decreased lipoprotein lipase activity (LPL) in the adipose tissue by 62% (p < 0.05), decreased adipocyte size by 27% (p < 0.01) and diminished the normal postovariectomy weight gain. Furthermore, estrogen treatment increased the nuclear estrogen receptor binding in adipocytes; in addition, there was a tendency for increased cytosolic estrogen receptor content as well. Time course studies revealed that already 6 h after a single estrogen injection the B_max increased from 3.82 ± 0.3 fmol/10⁶ cells to 9.8 ± 3.6 fmol/10⁶ cells (p < 0.1) and 24 h after a single injection the B_max was maximally increased to 12.7 ± 5.5 fmol/10⁶ cells (p < 0.05). The K_d was similar at all time points (about 3-5 nM). Furthermore, the specific insulin receptor binding was increased in adipocytes from estrogen treated rats. The specific insulin binding was maximally increased by 149 ± 6% (p < 0.001) after 4 days of daily estrogen injections. The increased binding seemed to be due to an increased number of insulin receptors on adipocytes from estrogen treated rats with no alteration of the ED₅₀ value. In conclusion it was found that estrogen treatment has a positive feedback effect on its own nuclear receptor. In addition, estrogen treatment was found to have several metabolic effects in the adipose tissue. Estrogen treatment increased the insulin receptor number, decreased LPL activity, increased the lipolytic response in adipocytes and finally decreased body weight and adipocyte cell size.