Nutrition-hormone receptor-gene interactions: implications for developmentand disease

Nutrition profoundly alters the phenotypic expression of a given genotype, particularly during fetal and postnatal development. Many hormones act as n utritional signals and their receptors play a key role in mediating the eff ects of nutrition on numerous genes involved in differentiation, growth and metabolism. Polypeptide hormones act on membrane-bound receptors to trigge r gene transcription via complex intracellular signalling pathways. By cont rast, nuclear receptors for lipid-soluble molecules such as glucocorticoids (GC) and thyroid hormones (TH) directly regulate transcription via DNA bin ding and chromatin remodelling. Nuclear hormone receptors are members of a large superfamily of transcriptional regulators with the ability to activat e or repress many genes involved in development and disease. Nutrition infl uences not only hormone synthesis and metabolism but also hormone receptors , and regulation is mediated either by specific nutrients or by energy stat us. Recent studies on the role of early environment on development have imp licated GC and their receptors in the programming of adult disease. Intraut erine 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 tr ansporters, uncoupling proteins and cation pumps. Such findings highlight a mechanism by which nutritional status can influence normal development, an d modify nutrient utilization, thermogenesis, peripheral sensitivity to ins ulin and optimal cardiac function. Diet and stage of development will also influence the transcriptional activity of drugs acting as ligands for nucle ar receptors. Potential interactions between nuclear receptors, including t hose for retinoic acid and vitamin D, should not be overlooked in intervent ion programmes using I or vitamin A supplementation of young and adult huma n populations.