DIFFERENTIAL AND TISSUE-SPECIFIC REGULATION OF (PRO)INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I MESSENGER-RNAS AND LEVELS OF THYROID-HORMONES IN GROWTH-RETARDED EMBRYOS

The control of embryonic growth in vertebrates appears to rely on the orchestrated action of several families of growth factors and hormones . The contribution of insulin-like growth factor (IGF-I) to prenatal g rowth regulation is better established in mammals than in other verteb rate species. The status of (pro)insulin gene product(s) in the pancre as and non-pancreatic tissues may be another important contribution to embryonic growth signals. We have characterized tissue sources of IGF -I gene and (pro)insulin gene mRNAs in normal chicken embryogenesis an d their changes in a model of avian growth retardation. We studied, by a highly sensitive reverse-transcription coupled to polymerase chain reaction (RT-PCR), the expression of IGF-I and (pro)insulin genes in b rain, pancreas, liver and eye in embryos from late organogenesis (E8) to late development (E17); hatching is at E20-21, a period of fast emb ryonic growth. In brain, pancreas and eye, growth-retarded embryos had lower IGF-I mRNA expression. In contrast, in the liver, little IGF-I mRNA was found during normal embryogenesis, but some early induction o ccurred in E17 growth-retarded embryos. (pro)insulin gene expression w as much lower in absolute levels in non-pancreatic tissues than in pan creas. However, it was developmentally regulated in brain, liver and e ye. The growth-retarded, IGF-I-deficient embryos had an increased expr ession of (pro)insulin mRNA in the brain. While IGF-I treatment of gro wth-retarded embryos increased their serum IGF-I values, only partial recovery of embryonic weight was obtained. Since abnormalities in othe r hormones may contribute to the failure of systemic IGF-I to reverse the retarded phenotype, thyroid hormones (T3 and T4) levels were deter mined in liver, brain and eye. They were markedly altered only in the liver of growth-retarded embryos, where an increase in thyroid hormone content was observed. We conclude that, in chicken embryos and possib ly other vertebrates, normal growth may implicate multiple hormones, i ncluding the concerted action, endocrine/paracrine, of IGF-I and (pro) insulin gene products.