The concentrations of plasma high density lipoprotein (HDL) and its subfraction HDL2 are influenced by endogenous and exogenous sex hormones. The catabolism of HDL2 is mediated by a lipolytic enzyme, hepatic lipase, which is present in endothelial cells covering the liver sinusoids. Since the activity of this enzyme is also regulated by gonadal and anabolic steroids, we examined whether the effect of sex steroids on plasma HDL is related to changes in hepatic lipase. In postmenopausal women, estradiol valerate (2 mg/day, orally) increased the HDL2 cholesterol and phospholipid concentrations by 20% (P less than 0.05). Simultaneously, the hepatic lipase activity of postheparin plasma decreased by 25% (P less than 0.05). The addition of levonorgestrel (250 micrograms/day, orally) to the treatment reversed both effects of estrogen, so that HDL2 cholesterol and phospholipid levels fell below and hepatic lipase activity rose above the respective pretreatment values. The hormones did not influence the HDL3 lipid concentrations or the lipoprotein lipase and lecithin:cholesterol acyltransferase activities. The results are compatible with the hypothesis that the effects of sex steroids on plasma HDL (HDL2) are mediated by changes in hepatic lipase activity.
The effects of oestradiol and levonorgestrel on plasma lipoprotein cholesterol (Chol) and triglyceride (Tg) levels and on postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activity were studied in 52 normolipoproteinaemic women. The androgen-derived progestin levonorgestrel increased postheparin plasma hepatic lipase (PH-HL) activity and decreased plasma high-density lipoprotein (HDL) lipid concentrations in a manner opposite to that of oestradiol. The relationships between PH-HL activity and HDL lipids suggest an important role for this enzyme as a mediator of sex hormone action on HDL.The sex differences in the distribution of plasma lipoproteins were demonstrated nearly three de¬ cades ago by Russ et al. ( 1951). Young women were shown to have a relatively greater amount of alpha lipoprotein (HDL) and a correspondingly smaller amount of beta lipoprotein (LDL) than young men. This stimulated the interest in the effects of sex hormones on plasma lipoproteins. Oestrogens were shown to increase alpha lipoprotein and decrease beta lipoprotein concentrations whereas androgens had the opposite effect (Russ et al. 1955). Also, oestrogens increased plasma very-low density lipo¬ protein (VLDL) concentrations whereas androgens reduced them (Furman et al. 1967). Later on nortestosterone-derived progestins were shown to have androgen-like effects on plasma lipoprotein levels (Silfverstolpe et al. 1979; Hirvonen et al. 1981), whereas progesterone and its dérivâtes were relatively inert in this respect (Svanborg & Vikrot 1966; Silfverstolpe et al. 1979; Hirvonen et al.
1981).The mechanism by which sex hormones exert their effects on plasma lipoprotein levels is not clear. Interestingly, they also influence postheparin plasma hepatic lipase (PH-HL) activity. Equine oestrogens have a marked suppressing effect on PH-HL activity whereas postheparin plasma lipo¬ protein lipase (PH-LPL) activity is not affected (Applebaum et al. 1977). A similar effect was observed during treatment with oestradiol valerate in hypercholesterolaemic post-menopausal women (Tikkanen et al. 1979). Conversely, the synthetic nortestosterone-derived progestin levonorgestrel is known to increase PH-HL activity (Tikkanen et al. 1981). In the present study we treated normo¬ lipoproteinaemic women with oestradiol and levo¬ norgestrel in order to clarify the possible role of hepatic lipase as mediator of sex hormone effects on lipoprotein lipids.
Material and MethodsThree groups of women received hormone therapy. In Group 1 women were given oestradiol only, in Group 2 they received levonorgestrel only and in Group 3 a combination of both was given. The women in all three groups had normal plasma lipoprotein levels prior to hormone treatment. The mean pre-treatment concentra¬ tions are given in Table 1. Apart from symptoms related Third Department ofMedicine1,
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