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Journal of Lipid Research, Vol 24, 303-315, Copyright © 1983 by Lipid Research, Inc.
DK Spady and JM Dietschy
This study was undertaken to measure and compare the rates at which
digitonin-precipitable sterols (DPS) were synthesized in vivo in the major
organs of five different animal species. These rates were assessed by
measuring the velocity at which [3H]water was incorporated into DPS in the
intact animal. The animals used were chosen to include species that carried
most of their plasma cholesterol either predominantly in high (rat,
hamster) or low (guinea pig) density lipoproteins (HDL and LDL,
respectively) or more evenly distributed between the LDL and HDL fractions
(monkey and rabbit). Whole animal sterol synthesis was much higher in the
rat (16.1 mumol/hr) than in the other four species (2.9-4.6 mumol/hr) when
normalized to a constant body weight of 100 g. This uniquely high rate of
sterol synthesis could be attributed predominantly to an extremely high
rate of incorporation of [3H]water into DPS by the liver of the rat. When
expressed per g of tissue, the highest content of newly synthesized sterol
in all species was found in tissues such as adrenal gland, ovary, and
gastrointestinal tract. However, the content of [3H]DPS in the liver varied
markedly from a high of 2279 nmol/hr per g in the rat to a low of only 109
nmol/hr per g in the guinea pig. Consequently, when expressed as a
percentage of total body synthesis, the whole liver of the rat contained
51% of the [3H]DPS while this figure was much lower in the monkey (40%),
hamster (27%), rabbit (18%), and guinea pig (16%). Thus, in all species
except the rat, the major sites for sterol synthesis appeared to be the
gastrointestinal tract, carcass (predominantly the muscle), and skin. In
addition, even though the content of newly synthesized sterol per g of
adrenal gland was higher than in nearly any other tissue in all of the
species examined, it was further demonstrated that in the rat most of this
[3H]DPS was derived from the blood (and, therefore, ultimately from the
liver) whereas in the other species it was largely synthesized locally
within the gland. Thus, these studies demonstrated that in many species the
liver is quantitatively far less important as a site for sterol synthesis
than previously believed and, as a correlate of this, most sterol utilized
by extrahepatic tissues is largely synthesized locally within those
tissues.
ARTICLES
Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat
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