Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 P316

SFEBES2009 Poster Presentations Steroids (36 abstracts)

Regulation of 11β-hydroxysteroid dehydrogenase type 1 activity in myocytes by differentiation stage, GH/IGF1 and glucocorticoids

CM Jones , M Sherlock , R Hardy , P Patel , PM Stewart & MS Cooper

School of Clinical & Experimental Medicine, University of Birmingham, Birmingham, UK.

GH/IGF1 stimulate muscle function whereas excess glucocorticoids induce myopathy. Myocytes express 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme which converts inactive cortisone to active cortisol. GH/IGF-I inhibit 11β-HSD1 expression in some tissues and thus reduce cellular glucocorticoid exposure. This suggests that anabolic actions of GH/IGF1 could be mediated indirectly through effects on 11β-HSD1. The regulation of 11β-HSD1 has been reported to be dependent on differentiation stage. The aim of this study was to determine the effects of GH/IGF-I+ glucocorticoids, on 11β-HSD1 activity in myocytes at early and late differentiation stages.

C2C12 murine myocytes were differentiated over eight days with or without corticosterone or dehydrocorticosterone (100 nM) and/or GH (100 ng/ml) or IGF-I (10 ng/ml). Treatments were administered at either day one or day three to assess effects at different stages of differentiation. 11βHSD1 activity was assessed at day eight using 100 nM cortisone and tritiated tracer followed by TLC and analysis using a Bioimager.

Untreated myocytes had 11β-HSD1 oxoreductase activity of 39.1+6.2 pmol/mg protein/hour (mean+S.E.M.). Myocytes exposed to IGF-I for eight days had activity of 7.0+0.9, increasing to 26.9+1.2 pmol/mg protein/hour if treatment was initiated at day three of differentiation. Treatment with GH followed the same pattern, increasing from 7.7+4.3 to 28.1+3.1 pmol/mg protein/hour (P<0.05). Withdrawing treatment at day three led to a decrease in activity to 3.3+0.8 and 4.4+0.5 pmol/mg protein/hour for IGF-I and GH respectively (P<0.05). The addition of corticosterone to GH or IGF-I treatments from day one of differentiation increased 11β-HSD1 activity at day eight to 13.5+1.9 and 14.9+3.9 pmol/mg protein/hour, respectively (P<0.05).

We have demonstrated divergent actions of GH and IGF-I on myocyte 11βHSD1 activity during early and late stages of differentiation. We also demonstrated glucocorticoid-induced increases in myocyte 11β-HSD1 activity. The effect of GH/IGF1 on muscle may thus, in part, be mediated indirectly through changes in glucocorticoid exposure.

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