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Nutrition–hormone receptor–gene interactions: implications for development and disease

Published online by Cambridge University Press:  28 August 2007

M. J. Dauncey*
Affiliation:
Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK
P. White
Affiliation:
Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK
K. A. Burton
Affiliation:
Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK
M. Katsumata
Affiliation:
Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK
*
*Corresponding author: Dr M. J. Dauncey, fax +44 1223 496023, email [email protected]
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Abstract

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Nutrition profoundly alters the phenotypic expression of a given genotype, particularly during fetal and postnatal development. Many hormones act as nutritional signals and their receptors play a key role in mediating the effects of nutrition on numerous genes involved in differentiation, growth and metabolism. Polypeptide hormones act on membrane-bound receptors to trigger gene transcription via complex intracellular signalling pathways. By contrast, nuclear receptors for lipid-soluble molecules such as glucocorticoids (GC) and thyroid hormones (TH) directly regulate transcription via DNA binding and chromatin remodelling. Nuclear hormone receptors are members of a large superfamily of transcriptional regulators with the ability to activate or repress many genes involved in development and disease. Nutrition influences not only hormone synthesis and metabolism but also hormone receptors, and regulation is mediated either by specific nutrients or by energy status. Recent studies on the role of early environment on development have implicated GC and their receptors in the programming of adult disease. Intrauterine growth restriction and postnatal undernutrition also induce striking differences in TH-receptor isoforms in functionally-distinct muscles, with critical implications for gene transcription of myosin isoforms, glucose transporters, uncoupling proteins and cation pumps. Such findings highlight a mechanism by which nutritional status can influence normal development, and modify nutrient utilization, thermogenesis, peripheral sensitivity to insulin and optimal cardiac function. Diet and stage of development will also influence the transcriptional activity of drugs acting as ligands for nuclear receptors. Potential interactions between nuclear receptors, including those for retinoic acid and vitamin D, should not be overlooked in intervention programmes using I or vitamin A supplementation of young and adult human populations.

Type
Micronutrient and Reprod. and Dev. Grps Sym. on relative contribution of diet and genotype to dev.
Copyright
Copyright © The Nutrition Society 2001

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