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J. Biol. Chem., Vol. 259, Issue 5, 2789-2797, 03, 1984
DB Jump, P Narayan, H Towle and JH Oppenheimer
We recently reported that 3,5,3'-triiodothyronine (T3) causes a rapid
increase in the translational activity of a specific mRNA (mRNAS14) coding
for a protein designated "Spot 14" (Mr = 18,000; 4.9 pI) using
two-dimensional gel electrophoresis of in vitro translated proteins. The
current studies suggest that Spot 14 is a cytosolic protein. Using a
plasmid-derived cDNAS14 and dot hybridization, we have directly measured
changes in hepatic mRNAS14 levels in response to T3 and other physiologic
stimuli. Following injection of hypothyroid rats with a receptor-saturating
dose of T3, a 20-min lag preceded the induction of hepatic mRNAS14 to
levels 16-fold above basal values within 4 h. This is the most rapid effect
of T3 on hepatic gene expression documented to date. Both during time
course studies in hypothyroid animals injected with T3 as well as in the
intact euthyroid rat, hepatic mRNAS14 levels varied up to 3-fold over a
24-h period in a pattern consistent with circadian variation. A lipogenic
diet also significantly elevated hepatic mRNAS14. Thus, T3, dietary, and
the unknown factors responsible for circadian variation influence hepatic
mRNAS14 expression. Blot and dot hybridization analysis indicated that
mRNAS14 expression in nonhepatic tissues was significantly below euthyroid
hepatic values. Responsivity of mRNAS14 in nonhepatic tissue to in vivo T3
administration was also either substantially diminished or totally absent.
Thus, expression and regulation of mRNAS14 is tissue specific.
Rapid effects of triiodothyronine on hepatic gene expression. Hybridization analysis of tissue-specific triiodothyronine regulation of mRNAS14
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