[Effects of estrogen and progestin on platelet-activating factor acetylhydrolase]

Platelet-activating factor (PAF) is one of the potent proinflammatory agents and is associated with a number of human diseases, including asthma, endotoxin shock and cardiovascular diseases. Additionally, plasma PAF acetylhydrolase (PAF-AH) activity to inactivate PAF is regulated by hormones. In this study, we elucidated the effects of estrogen and progestin on plasma PAF-AH and also the effects of PAF on rat tissues to investigate the mechanisms involved in the thrombotic episode. Plasma PAF-AH activity in female adult rats treated with 17 alpha-ethynylestradiol (50 micrograms/kg, 5 days) was decreased by 50%. However, medroxyprogesterone (50 mg/kg, 5 days) increased the enzyme activity by 50%. When PAF (5 to 60 nmol/kg) was injected intravenously into non-treated female adult rats, 80% of the animals died at 20 nmol/kg of PAF. Macroscopic findings showed hemorrhage, hyperemia and congestion in the lungs and heart, and necrosis-like change in the gastrointestines. Microscopically, thrombus was observed in the lungs and heart. When PAF was administered to female adult rats pretreated with sex steroid hormones, the mortality of the rats with low plasma PAF-AH activity caused by estrogen was increased, but decreased in the animals with high enzyme activity caused by progestin. These findings suggest that the imbalance between PAF and plasma PAF-AH is one of the mechanisms involved in the thrombotic episode, and estrogen and progestin are related to the event by regulating the plasma PAF-AH activity.