The Effects of 17β-Estradiol and Progesterone on the Metabolism of Free Fatty Acid by Perfused Livers from Normal Female and Ovariectomized Rats*

To determine whether any interaction occurs between progesterone and 17 beta-estradiol in the regulation of FFA metabolism by the liver, normal female rats were injected sc daily for 14 days with 7.5, 15, 50, or 100 microgram 17 beta-estradiol/kg, 25 mg progesterone/kg, 15 microgram 17 beta-estradiol plus 25 mg progesterone/kg, or vehicle (sesame oil) alone. To determine the effects of these hormones in the absence of endogenous estradiol and progesterone, ovariectomized rats were treated with the steroids. Livers were removed from the variously treated rats and perfused in vitro in a recycling system. An albumin-oleate complex was infused into the perfusate, providing a steady state concentration of 0.3--0.5 nM oleate. The uptake of FFA and output of ketone bodies and glucose by the livers were generally not altered by any of the steroid treatments. Neither these parameters nor triglyceride secretion was altered by ovariectomy. The administration of 15, 50, and 100 microgram estradiol/kg to normal, but not ovariectomized rats, increased triglyceride secretion. Progesterone alone had no effect on the secretion of triglyceride, but did antagonize the estradiol-mediated stimulation of triglyceride secretion in normal rats. The molar ratios of phospholipid to triglyceride and cholesterol to triglyceride of the very low density lipoprotein secreted by livers from normal females treated with estradiol were not altered, suggesting that the livers secreted more very low density lipoprotein particles of the same size. Based on the same criteria, livers from ovariectomized rats secreted smaller very low density lipoprotein particles compared to livers from control animals, an effect which was reversed by the administration of estradiol. We conclude that progesterone antagonizes the stimulation of hepatic triglyceride secretion by estradiol in normal female rats and that ovariectomy prevents this effect of progesterone.