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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.
Keywords
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Article info
Publication history
Accepted:
May 15,
1981
Received in revised form:
May 11,
1981
Received:
March 4,
1981
Footnotes
☆This investigation was supported by grants from the KROC Foundation and the National Institutes of Health 5 R01 HL12085-12.
Identification
Copyright
© 1982 Published by Elsevier Inc.