The hormonal regulation of platelet-activating factor acetylhydrolase activity in plasma

We have previously reported that certain fetal tissues including the lung and kidney have an increased platelet-activating factor (PAF) content and enzymatic mechanism for its elevated biosynthesis during the latter stages of pregnancy. In contrast, in the maternal plasma compartment of both the rabbit and human, a decreased capacity to inactivate PAF has been demonstrated. The PAF acetylhydrolase in the fetal plasma is also suppressed. The present study was undertaken to determine the mechanism(s) involved in the regulation of PAF acetylhydrolase. The 17α-ethynylestradiol was administered (intraperitoneal [i.p.] 2.5 mg/kg body wt 5 days) to female and male rats. The plasma PAF acetylhydrolase activity decreased 5-fold. A decrease was observed when a concentration of the estrogen as low as 50 μg/kg was employed. The injection of dexamethasone (i.p., 1.3 mg/kg body wt, 5 days) to male and female rats resulted in a 3-fold increase in the plasma PAF acetylhydrolase activity. The activity returned to the values prior to hormone treatment 4 days after cessation of treatment. Testosterone and progesterone were without effect on plasma acetylhydrolase activity. The change in PAF acetylhydrolase activity caused by estrogen and the glucocorticoid was reflected by a change in the activity in the HDL fraction and not due to the presence of an inhibitor or activator in the plasma of the hormone-treated animals. Human serum obtained from a group of women, in which the 17β-estradiol concentration was elevated in preparation for anin vitro fertilization procedure, showed an inverse relationship between the plasma estrogen concentration and the PAF acetylhydrolase activity. It is suggested that estrogen is responsible for the regulation of PAF acetylhydrolase and the decrease in the plasma PAF acetylhydrolase during the latter stages of pregnancy in both the maternal and fetal plasma caused by the hyperestrogenic state that occurs during this period. The observed increase in PAF acetylhydrolase by dexamethasone may account for, in part, the known anti-inflammatory properties of this steroid by decreasing the concentration of this potent autacoid. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.