Positive and Negative Effects of Hormones on Plasma Platelet-activating Factor Acetylhydrolase Activity

Abstract

Platelet-activating factor (PAF) is one of the potent proinflammatory agents and associated with a number of disorders, 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-A H activity in female adult rats treated with 17a -ethynylestradiol (50 pg/kg,5 days) was decreased by 50%. However, medroxyprogesterone (50 mg/kg,5 days) increased the enzyme activity by 50%. Plasma PAF-AH activity in female adult rats treated with either progeserone or 17a -hydroxyprogesterone (50 mg/kg,3 days) did not alter significantly. Both medroxyprogesterone and megestrol acetate (50 mg/kg,3 days) significantly increased plasma PAF-AH activity. However, both norethindrone acetate and norethynodrel (50 mg/kg,3 days)decreased the enzyme activity significantly.
When PAF (5 to 60 nmol/kg ) was injected intravenousely to nontreated female adult rats,80% of the animals died at 20 nmol/kg of PAF. Macroscopic findings showed hemorrhage, hyperemia and congestion in lung and heart and necrosis-like change in gastrointestine. Microscopically, thrombus was observed in lung and heart.
When PAF (10 nmol/kg) was administered to female adults rats pretreated with sex seroid hormones, the mortality of the rats with low plasma PAF-AH activity caused by 17a ethynylestradiol or norethindrone acetate was increased. These findings suggest that imbalance between PAF and plasma PAF-AH is one of the mechanisms involved in the thrombotic episode and that estrogen is related to the event by regulating the plasma PAF-AH activity. Additionally, some progestins, which have estrogenic effect on the enzyme activity, may be related to the thrombotic episode observed in oral contraceptive users.