Divergent regulation of proteasomes by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone.

Insulin-like growth factor I (IGF-I) and growth hormone (GH) exert their anabolic actions by increasing protein synthesis, but only IGF-I has been reported to impede protein breakdown. Using a model of myofibrillar catabolism produced by dexamethasone (Dex) we have reported that IGF-I down-regulates Dex-induced mRNAs for Ubiquitin (Ub) and Ub-conjugating enzymes (E2) in skeletal muscle, whereas GH had no significant effect. In the present study, we used the same model to determine whether IGF-I (0.35 mg/100 g BW) and/or GH (0.3 mg/100 g BW) have effects on proteasome subunit mRNAs in skeletal muscles of rats treated with Dex (0.5 mg/100 g BW) for 3 days. Dex caused significant increases in C-2, -3, and -8 proteasome subunit mRNAs (6.0-, 4.0-, and 6.6-fold increases, respectively). Injections of IGF-I in Dex-treated animals caused significant suppression of transcripts for C-2, -3, and -8 (32%, 42%, and 40%, respectively). GH restored the serum IGF-I levels in Dex treated animals, but caused further increases in proteasome subunit mRNAs (C-2, 35%; C-3, 34.5%; C-8, 33%; C-6, 42%; C-5, 32%; C-9, 37%). Administration of IGF-I in the Dex/GH-treated animals decreased the mRNAs of proteasome subunits in a manner and degree similar to those observed in the Dex/IGF-I group. Surprisingly, injection of GH alone in normal animals increased proteasome subunit mRNAs in skeletal muscle (C-2, 85%; C-3, 109%; C-8, 91%). This effect of GH on proteasome subunit mRNAs was also observed in liver. These findings suggest, therefore, that suppression of Dex-induced expression of proteasome subunit mRNAs in skeletal muscle is one of the mechanisms by which IGF-I exerts its antiproteolytic activity in catabolic states. On the other hand, the biological function of GH in regulating proteasome subunits needs further investigation.