Intrauterine events and the programming of adulthood disease: the role of fetal glucocorticoid exposure (Review).
There is increasing epidemiological evidence in humans which associates low birth weight with later cardiovascular and metabolic disorders including hypertension, insulin resistance, hyperlipidaemia and death from ischaemic heart disease. The molecular mechanisms underlying this link are unknown but fetal glucocorticoid exposure may play a role. In adult mammals, glucocorticoid hormones are involved in control of several physiological processes that maintain homeostasis including coordination of responses to stress. During development, glucocorticoids have important regulatory functions to prepare the organism for metabolic adaptations necessary for extrauterine life. Fetal glucocorticoid load is, in part, regulated by placental and fetal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which catalyses a rapid breakdown of maternal and fetal glucocorticoids into inert products. Supraphysiological doses of glucocorticoids retard fetal growth, and human intrauterine growth retardation is associated with elevated cortisol levels. Recent studies have shown that exposing rats to excessive glucocorticoids in utero reduces birth weight and causes permanent hypertension and hyperglycaemia in the adult offspring. These observations show that glucocorticoids could be the link between low birth weight and later disease. Understanding of the molecular details involved in prenatal glucocorticoid action may provide novel insights into the pathogenesis of common cardiovascular and metabolic disorders.
Nyirenda
M J
MJ
Molecular Endocrinology Laboratory, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, UK.
Seckl
J R
JR
D000328:Adult; D000818:Animals; D001724:Birth Weight; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000737:chemistry / Q000494:pharmacology*; D006706:Homeostasis; D006801:Humans; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D005938:Glucocorticoids