Regulation of components of the ubiquitin system by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone
D. Chrysis et Le. Underwood, Regulation of components of the ubiquitin system by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone, ENDOCRINOL, 140(12), 1999, pp. 5635-5641
To investigate whether the anabolic effects of insulin-like growth factor I
(IGF-I) and GH are mediated through regulation of the ubiquitin (Ub) pathwa
y, we examined the effect of IGF-I (0.35 mu g/100 g) and/or GH (0.3 mg/100
g BW) on the expression of Ub and Ub-conjugating (E2) enzyme messenger RNAs
(mRNAs) in skeletal muscle of rats made catabolic by treatment with dexame
thasone (Dex; 0.5 mg/100 g BW) for 3 days. Dex caused a significant loss of
body and gastrocnemius weight (14% and 25%, respectively) concurrent with
an increase in the 2.8- and 1.2-kb transcripts of Ub (14.3- and 12-fold inc
reases, respectively), the 1.8- and 1.2-kb transcripts of 14-kDa Ub-conjuga
ting enzyme (E2-14 kDa; 5.6- and 7.7-fold increases, respectively), the 4.4
- and 2.4-kb transcripts of Ub-E2G (6.5- and 8.2-fold increases, respective
ly), and the 2E isoform of the 17-kDa E2 mRNA (3.5-fold increase). Injectio
ns of IGF-I in Dex-treated animals ameliorated the body weight loss, and th
e gastrocnemius tended to be heavier. This improvement was also accompanied
by a significant suppression of transcripts for Uh (58% and 66% decreases)
, E2-14 kDa (58% and 68% decreases), and Ub-E2G (78% decrease), whereas the
2E isoform of the 17-kDa E2 was only modestly affected (20% decrease). GH
restored serum IGF-I levels to normal in Dex-treated rats, but had no effec
t on the body weight loss or on any of the studied components of the Ub pat
hway. Administration of IGF-I to the Dex/ GH-treated animals decreased the
activated mRNAs of the Ub pathway in a manner and degree similar to those o
bserved in the Dex/ IGF-I group.
In summary, these results provide evidence that IGF-I regulates the express
ion of mRNAs encoding components of the Ub pathway during catabolism and su
ggest a possible mechanism for the antiproteolytic actions of IGF-I; On the
other hand, GH, which is believed not to affect proteolysis but only prote
in synthesis, had no effect on any of the mRNAs studied.