[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.
Fujikami
F
F
Department of Obstetrics and Gynecology, Kansai Medical University, Osaka.
Yasuda
K
K
Sawaragi
I
I
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003276:Contraceptives, Oral / Q000009:adverse effects; D005260:Female; D008074:Lipoproteins / Q000097:blood; D010741:Phospholipases A / Q000097:blood*; D010972:Platelet Activating Factor / Q000378:metabolism*; D011372:Progestins / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000139:chemically induced
D003276:Contraceptives, Oral; D008074:Lipoproteins; D010972:Platelet Activating Factor; D011372:Progestins; D002784:Cholesterol; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase