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Journal of Lipid Research, Vol 37, 2332-2340, Copyright © 1996 by Lipid Research, Inc.
PA Kern, G Ranganathan, A Yukht, JM Ong and RC Davis
To better characterize the increase in lipoprotein lipase (LPL) translation
by hypothyroidism, adipocytes were prepared from control and hypothyroid
rats. Whereas LPL synthesis was higher in hypothyroid adipocytes, with no
change in mRNA levels, there was no increase in hormone-sensitive lipase
(HSL) synthesis. To determine whether a transacting translation regulatory
factor was present, a cytoplasmic fraction was prepared from control and
hypothyroid adipocytes, and added to an in vitro translation system
containing the hLPL mRNA. The hypothyroid cell fraction from adipose and
heart yielded an increase in LPL translation, when compared to control
extracts. Further experiments determined that the control adipocyte extract
contained a translation- inhibitory factor that was 8-fold lower in
activity in the hypothyroid extract. Using different LPL mRNA constructs in
the in vitro translation reaction, the region that controlled translation
was localized to nucleotides 1599 to 1638 (proximal 3' untranslated region
(UTR)). To confirm the presence of a transacting factor, a sense RNA strand
corresponding to this region was added to the in vitro translation
reaction. This sense strand competed for the transacting factor in the
control cell extract, yet had no effect on the hypothyroid cell extract.
Thus, there is a translation repressor factor in the cytoplasm of rat
adipocytes, and this factor is greatly reduced in activity in hypothyroid
rat adipocytes. Because a similar mechanism of LPL regulation occurs in
response to epinephrine, the absence of the translation repressor may be a
mechanism for the loss of sensitivity of hypothyroid cells for
catecholamines.
ARTICLES
Translational regulation of lipoprotein lipase by thyroid hormone is via a cytoplasmic repressor that interacts with the 3' untranslated region
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.
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