Hormonal regulation of platelet-activating factor-acetyltransferase activity in rat tissues

Platelet-activating factor (PAF) plays a very important role in a number of physiological or pathological conditions. Recently, we and others have suggested that the PAF concentration in various tissues may be regulated by the enzyme that inactivates PAF, PAF acetylhydrolase (PAF-AH). Furthermore, it has been shown that the plasma isozyme of PAF-AH is regulated by various steroid hormone. Lyso-PAF:acetyl-CoA acetyltransferase (PAF-AT) is a key enzyme in PAF biosynthesis by the remodeling pathway. In the present study, the hormonal effects on the tissue levels of PAF-AT activity were investigated in various organs of the rat. The microsomal fraction was prepared from the spleen, lung, uterus, and liver of female rats which had been pretreated with dexamethasone, 17 alpha-ethynylestradiol, medroxyprogesterone-acetate, or vehicle and the PAF-AT activity was assayed. The rats treated with dexamethasone demonstrated significantly lower PAF-AT specific activity in the liver (P < 0.001) and spleen (P < 0.01), compared to the control group. A dose-dependent decrease of PAF-AT specific activity was demonstrated following dexamethasone treatment. Medroxyprogesterone injection also caused a significant decrease of PAF-AT activity in the liver (P < 0.01). No change of PAF-AT activity in any tissue was observed in the 17 alpha-ethynylestradiol-injected animals. Plasma PAF-AH activity was increased significantly by the administration of dexamethasone (P < 0.001) or medroxyprogesterone (P < 0.001), and decreased by 17 alpha-ethynylestradiol (P < 0.001), as previously described. The observation that dexamethasone or medroxyprogesterone treatment decreases the activity of PAF-AT and increases the plasma PAF-AH activity provides a mechanism for the tight control of PAF in tissues.