Acute treatment with corticosteroids decreases IGF-1 and IGF-2 expression in the rat diaphragm and gastrocnemius.

Massive doses of methylprednisolone (M) or triamcinolone (T) induced diaphragmatic type IIx/b atrophy, resulting in a leftward shift of the force-frequency curve in rats (). To examine the role of insulin-like growth factors (IGFs) in these changes, IGF mRNA content was measured in costal diaphragm, gastrocnemius, and liver removed from 32 rats treated daily during 5 d either with saline (control, C and pair-fed, PF), M, or T (80 mg/kg). Blood samples were taken to measure IGF-1 serum levels. RNA levels were measured by Northern and dot-blots after hybridization with rat IGF-1 or IGF-2 cDNA probes labeled with alpha-32P. Compared with C (845 +/- 128 ng/ml), IGF-1 serum levels were significantly decreased in M (699 +/- 90 ng/ml, p < 0.001 versus C) and PF animals (505 +/- 33 ng/ml, p < 0.001 versus others) and even more so, in T-treated animals (273 +/- 134 ng/ml, p < 0.001 versus others). Along the same lines, IGF-1 expression in the liver was depressed after corticosteroid treatment and in PF, whereas IGF-2 mRNA content remained unchanged. Compared with C, the relative expression of IGF-1 mRNA in the diaphragm was depressed by 44% and 69% in the M and T groups, respectively (p < 0.0001 versus C), while it was unchanged in PF animals. In the gastrocnemius, IGF-1 expression was reduced after M and T (-51% and -59%, respectively, p < 0.0001 versus C) as well as in PF animals (-40%, p < 0.001 versus C). For IGF-2, a similar pattern of expression was found in the diaphragm and the gastrocnemius. Indeed, IGF-2 mRNA tended to decrease in corticosteroid-treated rats (NS) whereas it was unchanged in PF rats. We conclude that decreased IGF expression after corticosteroid treatment was similar in diaphragm and gastrocnemius and may be responsible for the diaphragmatic changes observed after steroid treatment.

[1]  H. Werner,et al.  Regulation by fasting of rat insulin-like growth factor I and its receptor. Effects on gene expression and binding. , 1989, The Journal of clinical investigation.

[2]  S. Mccune,et al.  Insulin-like growth factor mRNA expression in tissues of lean and obese male SHFF/Mcc-facp rats , 1994 .

[3]  C. Brown,et al.  IGF-I, a marker of undernutrition in hemodialysis patients. , 1990, The American journal of clinical nutrition.

[4]  M. Dodson,et al.  Ovine somatomedin, multiplication-stimulating activity, and insulin promote skeletal muscle satellite cell proliferation in vitro. , 1985, Endocrinology.

[5]  H. Vandenburgh,et al.  Insulin and IGF-I induce pronounced hypertrophy of skeletal myofibers in tissue culture. , 1991, The American journal of physiology.

[6]  E. Froesch,et al.  Actions of insulin-like growth factors. , 1985, Annual review of physiology.

[7]  K. Brismar,et al.  Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects. , 1994, The Journal of clinical endocrinology and metabolism.

[8]  M. Weinmann,et al.  Myopathy in severe asthma. , 1992, The American review of respiratory disease.

[9]  D. Clemmons,et al.  Serum concentrations of insulin-like growth factor II are not changed by short-term fasting and refeeding. , 1988, The Journal of clinical endocrinology and metabolism.

[10]  W. Blum,et al.  The evolution of changes in immunoreactive serum insulin-like growth factors (IGFs), IGF-binding proteins, circulating growth hormone (GH) and GH-binding protein as a result of short-term dexamethasone treatment. , 1994, The Journal of endocrinology.

[11]  R. Furlanetto,et al.  Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. , 1977, The Journal of clinical investigation.

[12]  M. Fournier,et al.  Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats. , 1997, Journal of applied physiology.

[13]  L. Dickinson,et al.  Effects of dietary composition on somatomedin activity in growing rats. , 1979, The Journal of nutrition.

[14]  D. Clemmons,et al.  Failure of insulin-like growth factor-I (IGF-I) infusion to promote growth in protein-restricted rats despite normalization of serum IGF-I concentrations. , 1991, Endocrinology.

[15]  M. Hamilton,et al.  No effect of aging on skeletal muscle insulin-like growth factor mRNAs. , 1995, The American journal of physiology.

[16]  M. Decramer,et al.  Effects of acute steroid administration on ventilatory and peripheral muscles in rats. , 1996, American journal of respiratory and critical care medicine.

[17]  R. Rogers,et al.  Effects of growth hormone on diaphragmatic recovery from malnutrition. , 1992, Journal of applied physiology.

[18]  J. Frystyk,et al.  Free insulin‐like growth factors (IGF‐I and IGF‐II) in human serum , 1994, FEBS letters.

[19]  G. Glazner,et al.  Insulinlike growth factor gene expression in rat muscle during reinnervation , 1995, Muscle & nerve.

[20]  W S David,et al.  Muscle weakness in mechanically ventilated patients with severe asthma. , 1996, American journal of respiratory and critical care medicine.

[21]  L. Phillips,et al.  Response of IGF-1 to nutritional support in malnourished hospital patients: a possible indicator of short-term changes in nutritional status. , 1989, The American journal of clinical nutrition.

[22]  L. Mathews,et al.  Regulation of insulin-like growth factor-I and growth hormone receptor gene expression by diabetes and nutritional state in rat tissues. , 1989, The Journal of endocrinology.

[23]  P. Bechtel,et al.  Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth. , 1990, The American journal of physiology.

[24]  J. Ketelslegers,et al.  Decreased serum insulin-like growth factor I response to growth hormone in hypophysectomized rats fed a low protein diet: evidence for a postreceptor defect. , 1988, Acta endocrinologica.

[25]  D. Clemmons,et al.  Identification of the types of insulin-like growth factor-binding proteins that are secreted by muscle cells in vitro. , 1989, The Journal of biological chemistry.

[26]  F. Haddad,et al.  The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. , 1996, Journal of applied physiology.

[27]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[28]  B. Moats-Staats,et al.  Reduced serum concentrations of insulin-like growth factor-I (IGF-I) in protein-restricted growing rats are accompanied by reduced IGF-I mRNA levels in liver and skeletal muscle. , 1991, The Journal of endocrinology.

[29]  W. Lee,et al.  Measurement of insulin-like growth factor-II in physiological fluids and tissues. II. Extraction quantification in rat tissues. , 1991, Endocrinology.

[30]  G. Glazner,et al.  Elevated insulin-like growth factor (IGF) gene expression in sciatic nerves during IGF-supported nerve regeneration. , 1994, Brain research. Molecular brain research.

[31]  R. Furlanetto,et al.  [20] Radioimmunoassay of somatomedin C/insulin-like growth factor I , 1987 .

[32]  L. Phillips,et al.  7 Somatomedin activity in disorders of nutrition and metabolism , 1984 .

[33]  P. Bechtel,et al.  Induction of mRNA for IGF-I and -II during growth hormone-stimulated muscle hypertrophy. , 1988, The American journal of physiology.

[34]  D. Clemmons,et al.  Regulation of somatomedin-C/insulin-like growth factor I by nutrients. , 1986, Hormone research.

[35]  M. Thorén,et al.  Somatomedin A levels in patients with Cushing's disease. , 1981, Acta endocrinologica.

[36]  M. Binoux,et al.  Serum somatomedin/insulin-like growth factor (IGF) and IGF carrier levels in patients with Cushing's syndrome or receiving glucocorticoid therapy. , 1982, The Journal of clinical endocrinology and metabolism.