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Influence of genetic hyperlipemia in the zucker rat upon the lipemic response to graded estradiol exposure

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      Abstract

      The present investigation was designed to examine the influence of genetic Type IV hyperlipoproteinemia on the metabolism of lipids in response to estrogen exposure.
      The influence of 17-β-estradiol was examined in a dose-response study over a range of hormone concentration from 10 to 100 pg/ml in genetic hyperlipidemic Zucker rats. In oophorectomized female rats, replacement levels of plasma estradiol of 40 pg/ml resulted in maximal hypertriglyceridemia of approximately 500 mg/dl representing a 5-fold exaggeration of that observed in control genetically normo-lipemic animals. This hypertriglyceridemia was associated with an increased production of triglyceride (TG) in excess of clearance, with a resulting production : clearance ratio of approximately 1.5. Exposure to maximum blood levels of estradiol, approximately 100 pg/ml, resulted in subnormal levels of plasma TG (∼145 mg/dl) in association with a reduced production: clearance ratio of approximately 0.36.
      In contrast to the marked hypocholesterolemic response to maximum estrogen exposure seen in normolipemic animals, the genetic Type IV hyperlipemic animal failed to demonstrate reduced plasma cholesterol concentration. This phenomenon was related to a rise in plasma LDL concentration in conjunction with parallel reduction in plasma HDL2 levels. Thus, an abnormal ratio of excessive LDL : HDL emerged in response to estrogen exposure in this model of human Type IV lipemia. This observation suggests that the genetic predisposition of the host may be critical to both the quantitative as well as the qualitative response to estrogen.

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