Differential and tissue-specific regulation of (pro)insulin and insulin-like growth factor-I mRNAs and levels of thyroid hormones in growth-retarded embryos.

Abstract

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 growth regulation is better established in mammals than in other vertebrate species. The status of (pro)insulin gene product(s) in the pancreas 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 and 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 brain, pancreas, liver and eye in embryos from late organogenesis (E8) to late development (E17); hatching is at E20-21, a period of fast embryonic 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 occurred in E17 growth-retarded embryos. (pro)insulin gene expression was much lower in absolute levels in non-pancreatic tissues than in pancreas. However, it was developmentally regulated in brain, liver and eye. The growth-retarded, IGF-I-deficient embryos had an increased expression of (pro)insulin mRNA in the brain. While IGF-I treatment of growth-retarded embryos increased their serum IGF-I values, only partial recovery of embryonic weight was obtained. Since abnormalities in other hormones may contribute to the failure of systemic IGF-I to reverse the retarded phenotype, thyroid hormones (T3 and T4) levels were determined 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 possibly other vertebrates, normal growth may implicate multiple hormones, including the concerted action, endocrine/paracrine, of IGF-I and (pro)insulin gene products.