Regulation of hepatic insulin-like growth factor I leader exonusage in lambs: effect of immunization against growth hormone-releasing factor and subsequent growth hormone treatment
| Autor: | Tadge Szestak, Jennifer M. Pell, D. C. O'Sullivan |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Gene Expression Biology Growth Hormone-Releasing Hormone Weight Gain Antibodies Insulin-like growth factor Exon Internal medicine Genetics medicine Animals Endocrine system RNA Messenger Insulin-Like Growth Factor I Messenger RNA Sheep Alternative splicing Age Factors Exons General Medicine Growth hormone secretion Insulin-Like Growth Factor Binding Proteins Growth hormone treatment Alternative Splicing Endocrinology Liver Growth Hormone Body Composition Immunization Animal Science and Zoology medicine.symptom Weight gain Food Science |
| Zdroj: | Journal of Animal Science. 80:1074-1082 |
| ISSN: | 1525-3163 0021-8812 |
| DOI: | 10.2527/2002.8041074x |
| Popis: | The establishment of a GH-responsive endocrine IGF-I network is essential for the regulation of postnatal growth. Transcripts of exons 1 and 2 of the mammalian IGF-I gene are alternately spliced onto exon 3, generating class 1 and class 2 mRNA, respectively, each encoding individual signal peptides. The liver is largely responsible for the synthesis of circulating IGF-I and is the main site of expression for class 2 mRNA. The aim of this study was to examine the regulation of hepatic class 1 and 2 mRNA levels in response to changed GH status. Lambs were actively immunized against GRF to suppress GH secretion; hepatic IGF-I mRNA leader exon usage was examined in the presence and absence of GH replacement and in control-immunized lambs. Lambs immunized against GRF exhibited a 17% (P < 0.001) decrease in growth rate as assessed by whole body weight gain, accompanied by decreased circulating IGF-I concentrations (P < 0.001), which were increased by subsequent GH treatment (P < 0.001). Hepatic class 1 and 2 IGF-I mRNA levels decreased in GRF-immunized lambs, although only class 2 transcripts decreased significantly (P < 0.001). Subsequent GH treatment induced increases in class 1 and 2 mRNA levels (P < 0.001) but the increase in class 2 message exceeded that for class 1 (P < 0.001). Thus, the percentage of total IGF-I mRNA accounted for by class 2 mRNA was 45% in control lambs, decreased to less than 20% in GRF-immunized lambs, but increased to 72% in the GRF-immunized lambs treated with GH and correlated with circulating IGF-I concentrations. These data suggest physiological significance for class 1 and 2 IGF-I mRNA species in GH action. Possible functions for such alternative splicing mechanisms are discussed. |
| Databáze: | OpenAIRE |
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