Preliminary report: Kinetic studies on the modulation of high-density lipoprotein, apolipoprotein, and subfraction metabolism by sex steroids in a postmenopausal woman

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To investigate the effects of estrogens and androgens on the metabolism of high density lipoproteins (HDL) and low density lipoproteins (LDL), a normolipidemic postmenopausal woman was studied under the following conditions: (1) during supplementation with ethinyl estradiol (0.06 mg/d); (2) without sex steroid therapy; and (3) during treatment with stanozolol, an androgenic, anabolic steroid (6 mg/d). During these manipulations HDL and LDL cholesterol levels fluctuated widely but reciprocally: during estrogen supplementation HDL increased while LDL decreased; during stanozolol HDL-C decreased while LDL-C increased. Simultaneous changes in post-heparin plasma hepatic triglyceride lipase activity paralleled those of LDL (and opposed those of HDL), decreasing with estrogen and increasing with stanozolol. During all three phases, autologous 125I-HDL turnover studies disclosed similarities between HDL 2 and apolipoprotein A-I metabolism and between HDL 3 and apolipoprotein A-II metabolism. In the untreated state the residence times of HDL 2 and apo A-I were only half those of HDL 3 and apo A-II. During estrogen treatment HDL 2 and apo A-I, residence times were selectively prolonged, coming to resemble those of HDL 3 and apo A-II, which remained unchanged. By contrast, during stanozolol treatment HDL 3 and apo A-II residence times were selectively reduced, coming to resemble those of HDL 2 and apo A-I, which remained unchanged. Apo A-I levels increased on estrogen and decreased on stanozolol, while apo A-II remained stable. Hence, estrogen increased HDL primarily by retarding the catabolism of the HDL 2 subfraction rich in apo A-I, whereas stanozolol decreased HDL by accelerating the catabolism of HDL 3, relatively rich in apo A-II. These effects may have been mediated via the concomitant sex steroid-induced changes in the activity of hepatic triglyceride lipase, hypothesized to be a central enzyme in the regulation of HDL catabolism.