ROLE OF FEMALE SEX STEROIDS IN REGULATING CHOLESTERYL ESTER TRANSFER PROTEIN IN TRANSGENIC MICE

The role of sex steroids in the regulation of cholesteryl ester transf er protein (CETP) was examined in the following groups of female trans genic mice carrying the human CETP gene: (1) normal, (2) ovariectomize d, (3) ovariectomized and treated with estrogen; (4) ovariectomized an d treated with progesterone; (5) ovariectomized and treated with both hormones, and (6) ovariectomized and treated with tamoxifen. CETP acti vity was measured in the plasma, and in the particulate and the solubl e fractions of liver, muscle, and adipose tissue, Human CETP specific activity was determined by taking the difference of cholesterol ester transfer in the presence and absence of an antibody (TP2) against huma n CETP. Ovariectomy reduced hormone levels, but did not completely abo lish them from the circulation. Plasma CETP activity was significantly reduced in the tamoxifen group. There were significant reductions in CETP in liver homogenate and the soluble fraction, as well as in the p articulate fraction of adipose with ovariectomy. Hormone replacement d id not restore CETP activity in either the plasma or the tissues, Tamo xifin treatment resulted in a decrease in CETP activity in both fracti ons of liver, but had no effect on adipose. In the soluble fraction of adipose tissue and both fractions of muscle, only trace CETP activity was detected. We conclude that (1) minimal amounts of sex steroid hor mones may be sufficient to affect CETP expression; (2) the effects of sex steroid hormones vary among tissues; and (3) in addition to the se x steroids, factor(s) from the ovary are needed for the full expressio n of CETP in this animal model. Copyright (C) 1998 by W.B. Saunders Co mpany.