[Positive and negative effects of progestins on platelet-activating factor acetylhydrolase activity in rat plasma]

Platelet-activating factor acetylhydrolase (PAF-AH), the enzyme that inactivates PAF, is regulated by steroid hormones including progestin. It has been reported that 17 alpha-ethynylestradiol decreases plasma PAF-AH activity and medroxyprogesterone increases the enzyme activity. In this study, we elucidated the effects of various progestins on plasma PAF-AH activity and lipoprotein cholesterol levels. Plasma PAF-AH activity in female adult rats treated with either progesterone or 17 alpha-hydroxyprogesterone (50mg/kg, 3 days) did not change significantly. Both medroxyprogesterone and megestrol acetate (50mg/kg, 3 days) significantly increased plasma PAF-AH activity, but both norethindrone acetate and norethynodrel (50mg/kg, 3 days) significantly decreased the enzyme activity. In addition, not only did medroxyprogesterone increase plasma PAF-AH activity but plasma lipoprotein cholesterol and norethindrone acetate decreased both of them. A significant correlation between plasma PAF-AH activity and the lipoprotein level was found (r = 0.974, p < 0.01). When PAF (10nmol/kg) was administered to female adult rats pretreated with progestins, the mortality of the rats that had low plasma PAF-AH activity due to norethindrone acetate was increased in the same manner as observed in the 17 alpha-ethynylestradiol-pretreated group. These findings indicate that progestins have various effects on plasma PAF-AH activity and the lipoprotein level. In addition, some progestins, which have an estrogenic effect on enzyme activity, may be related to the thrombotic episodes observed in oral contraceptive users.