Short-term growth hormone or IGF-I administration improves the IGF-IGFBP system in arthritic rats. 2012

M López-Menduiña, and A I Martín, and E Castillero, and M A Villanúa, and A López-Calderón
Department of Physiology, Faculty of Medicine, Complutense University, Avda. Complutense s/n. 28040 Madrid, Spain.

OBJECTIVE Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that inhibits the GH-IGF-I axis and decreases body weight gain and muscle mass. Although chronic GH or IGF-I treatment increases body weight gain in arthritic rats, muscle resistance to GH and IGF-I is a very common complication in inflammatory diseases. In this study we examine the effect of short-term administration of rhGH and rhIGF-I on liver and muscle IGF-I, IGFBP-3 and -5 as well as on the ubiquitin-ligases MuRF1 and atrogin-1 in the muscle of arthritic rats. METHODS Arthritis was induced in adult male Wistar rats by an intradermal injection of 4 mg of Freund's adjuvant. Fifteen days after adjuvant injection, 300 μg/kg of rhGH or 200 μg/kg of rhIGF or saline was administrated 18 and 3h before decapitation. A pair-fed group injected with saline was included in order to discard a possible effect of decreased food intake. Gene expression of IGF-I, GHR, IGFBP-3, IGFBP-5, atrogin-1 and MuRF1 were quantified using RT-PCR. In serum, IGF-I was measured by radioimmunoassay (RIA) and IGFBP-3 by ligand blot. RESULTS Arthritis decreased serum IGF-I and IGF mRNA in liver (P<0.05), but not in skeletal muscle. In arthritic rats, rhGH increased serum IGF-I and liver IGF-I mRNA similar to the levels of pair-fed rats. Arthritis increased atrogin-1, MuRF1, IGFBP-3 and IGFBP-5 mRNA in muscle (P<0.01). IGFBP-3 mRNA was downregulated by rhIGF-I, but not by rhGH, administration in control and arthritic rats (P<0.05). Administration of rhGH and rhIGF-I increased IGFBP-5 in the gastrocnemius of arthritic rats. CONCLUSIONS Short-term rhGH and rhIGF-I administration was found to increase muscle IGFBP-5 mRNA, whereas only rhIGF-I administration decreased muscle IGFBP-3 mRNA in control and arthritic rats. These data suggest that arthritis does not induce GH or IGF-I resistance in skeletal muscle.

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008297 Male Males
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001169 Arthritis, Experimental ARTHRITIS that is induced in experimental animals. Immunological methods and infectious agents can be used to develop experimental arthritis models. These methods include injections of stimulators of the immune response, such as an adjuvant (ADJUVANTS, IMMUNOLOGIC) or COLLAGEN. Adjuvant Arthritis,Arthritis, Adjuvant-Induced,Arthritis, Collagen-Induced,Arthritis, Adjuvant,Collagen Arthritis,Arthritides, Collagen,Arthritis, Collagen,Collagen Arthritides,Collagen-Induced Arthritides,Collagen-Induced Arthritis
D013006 Growth Hormone A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized. Growth Hormone, Recombinant,Pituitary Growth Hormone,Recombinant Growth Hormone,Somatotropin,Somatotropin, Recombinant,Growth Hormone, Pituitary,Growth Hormones Pituitary, Recombinant,Pituitary Growth Hormones, Recombinant,Recombinant Growth Hormones,Recombinant Pituitary Growth Hormones,Recombinant Somatotropins,Somatotropins, Recombinant,Growth Hormones, Recombinant,Recombinant Somatotropin
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018482 Muscle, Skeletal A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles
D018969 Insulin-Like Growth Factor Binding Proteins A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9) IGF Binding Protein,IGF-Binding Protein,IGF-Binding Proteins,IGFBP,Insulin-Like Growth Factor Binding Protein,Somatomedin-Binding Protein,Somatomedin-Binding Proteins,Binding Protein, IGF,IGF Binding Proteins,Insulin Like Growth Factor Binding Protein,Protein, IGF Binding,Protein, IGF-Binding,Protein, Somatomedin-Binding,Somatomedin Binding Protein,Somatomedin Binding Proteins
D018972 Insulin-Like Growth Factor Binding Protein 3 One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level. IGF-Binding Protein 3,IGFBP-3,IGF Binding Protein 3,Protein 3, IGF-Binding

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