Prenatal programming of postnatal endocrine responses by glucocorticoids.

Epidemiological studies have led to the hypothesis that a major component of the risk of diseases such as hypertension, coronary heart disease and non-insulin-dependent diabetes (the 'metabolic syndrome') is established before birth. Although the underlying mechanisms of this 'programming' of disease have not yet been conclusively determined, a reduced fetal nutrient supply as a consequence of poor placental function or unbalanced maternal nutrition is strongly implicated. It has been proposed that one outcome of suboptimal nutrition is exposure of the fetus to excess glucocorticoids, which restrict fetal growth and programme permanent alterations in its cardiovascular, endocrine and metabolic systems. This review focuses on the effects of endogenous and exogenous glucocorticoid exposure in utero on postnatal hypothalamo-pituitary-adrenal (HPA) axis activity, both in humans and experimental animals. The physiological consequences and proposed underlying molecular and cellular mechanisms are discussed. Current data indicate that key targets for programming may include not only the HPA axis but also glucocorticoid receptor gene and 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) gene expression in a range of tissues.

[1]  B. Levin,et al.  The obesity epidemic: metabolic imprinting on genetically susceptible neural circuits. , 2000, Obesity research.

[2]  M. Dodic,et al.  Can Excess Glucocorticoid, in Utero, Predispose to Cardiovascular and Metabolic Disease in Middle Age? , 1999, Trends in Endocrinology & Metabolism.

[3]  Jeffrey S. Robinson,et al.  Placental Restriction Alters the Functional Development of the Pituitary-Adrenal Axis in the Sheep Fetus during Late Gestation , 1996, Pediatric Research.

[4]  M. Morgan,et al.  Multiple courses of antenatal corticosteroids and outcome of premature neonates. North American Thyrotropin-Releasing Hormone Study Group. , 1999, American journal of obstetrics and gynecology.

[5]  G. Liggins,et al.  A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. , 1972, Pediatrics.

[6]  C. Yajnik,et al.  -to: Hales CN, Barker DJP (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35:595–601 , 2003, Diabetologia.

[7]  M. Le Moal,et al.  Maternal Glucocorticoid Secretion Mediates Long-Term Effects of Prenatal Stress , 1996, The Journal of Neuroscience.

[8]  J. Seckl,et al.  Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. , 1996, Neuroendocrinology.

[9]  D. Barker,et al.  The thrifty phenotype hypothesis. , 2001, British medical bulletin.

[10]  D. Gardner,et al.  Intrauterine programming of hypertension: the role of the renin-angiotensin system. , 1999, Biochemical Society transactions.

[11]  K. Godfrey,et al.  High-Meat, Low-Carbohydrate Diet in Pregnancy: Relation to Adult Blood Pressure in the Offspring , 2001, Hypertension.

[12]  D. Sloboda,et al.  The fetal placental hypothalamic–pituitary–adrenal (HPA) axis, parturition and post natal health , 2001, Molecular and Cellular Endocrinology.

[13]  E. Lambert,et al.  Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young south african adults: early programming of cortisol axis. , 2000, The Journal of clinical endocrinology and metabolism.

[14]  J. Mason,et al.  Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis. , 1995, The Journal of clinical endocrinology and metabolism.

[15]  B. Walker,et al.  Altered control of cortisol secretion in adult men with low birth weight and cardiovascular risk factors. , 2001, The Journal of clinical endocrinology and metabolism.

[16]  M. Kilby,et al.  OUTSTANDING CONTRIBUTION 11 β-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction , 1998 .

[17]  R. Sapolsky,et al.  Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion. , 1996, Stress.

[18]  M. Kilby,et al.  Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms. , 2001, The Journal of clinical endocrinology and metabolism.

[19]  L. Gurrin,et al.  The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function. , 2002, The Journal of endocrinology.

[20]  S. Shelton,et al.  Neurotoxicity of Glucocorticoids in the Primate Brain , 1994, Hormones and Behavior.

[21]  D. Gardner,et al.  Maternal protein restriction influences the programming of the rat hypothalamic-pituitary-adrenal axis. , 1996, The Journal of nutrition.

[22]  E. Wintour,et al.  Organs/Systems Potentially Involved In One Model Of Programmed Hypertension In Sheep , 2001, Clinical and experimental pharmacology & physiology.

[23]  S. Langley-Evans.  Maternal carbenoxolone treatment lowers birthweight and induces hypertension in the offspring of rats fed a protein-replete diet. , 1997, Clinical science.

[24]  L. Poston,et al.  Vasodilation to Vascular Endothelial Growth Factor in the Uterine Artery of the Pregnant Rat Is Blunted by Low Dietary Protein Intake , 2002, Pediatric Research.

[25]  D. Gardner,et al.  Maintenance of maternal diet-induced hypertension in the rat is dependent on glucocorticoids. , 1997, Hypertension.

[26]  A. Mccrea,et al.  Stress during pregnancy alters the offspring hypothalamic, pituitary, adrenal, and testicular response to isolation on the day of weaning. , 1999, Neurotoxicology and teratology.

[27]  L. Doyle,et al.  Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children. , 2000, Clinical science.

[28]  J. Seckl,et al.  Glucocorticoids, feto-placental 11β-hydroxysteroid dehydrogenase type 2, and the early life origins of adult disease , 1997, Steroids.

[29]  N. Copin,et al.  Printed in U.S.A. Copyright © 2001 by The Endocrine Society The Maternal Diet during Pregnancy Programs Altered Expression of the Glucocorticoid Receptor and Type 2 11�-Hydroxysteroid Dehydrogenase: Potential Molecular Mechanisms Underlying the Programmin , 2022 .

[30]  J. Newnham.  Is Prenatal Glucocorticoid Administration Another Origin Of Adult Disease? , 2001, Clinical and experimental pharmacology & physiology.

[31]  M. Novy,et al.  Dexamethasone and estradiol treatment in pregnant rhesus macaques: effects on gestational length, maternal plasma hormones, and fetal growth. , 1983, American journal of obstetrics and gynecology.

[32]  L. Gurrin,et al.  Programming effects in sheep of prenatal growth restriction and glucocorticoid exposure. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[33]  M. Hanson,et al.  Effect of maternal nutrient restriction in early gestation on development of the hypothalamic-pituitary-adrenal axis in fetal sheep at 0.8-0.9 of gestation. , 1999, The Journal of endocrinology.

[34]  M A Hanson,et al.  Dietary restriction in pregnant rats causes gender‐related hypertension and vascular dysfunction in offspring , 2001, The Journal of physiology.

[35]  P. Sly,et al.  Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs. , 1997, American journal of respiratory and critical care medicine.

[36]  C. Ducsay,et al.  Changes in ovine fetal adrenocortical responsiveness after long-term hypoxemia. , 1993, The American journal of physiology.

[37]  J. Seckl,et al.  Inhibition of 11β‐hydroxysteroid dehydrogenase, the foeto‐placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety‐like behaviour in the offspring , 2000, The European journal of neuroscience.

[38]  S. Matthews,et al.  A Short Period of Maternal Nutrient Restriction in Late Gestation Modifies Pituitary-Adrenal Function in Adult Guinea Pig Offspring , 2001, Neuroendocrinology.

[39]  M. Meaney,et al.  5'-heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: differential regulation of variant transcripts by early-life events. , 2000, Molecular endocrinology.

[40]  R. Benediktsson,et al.  Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? , 1993, The Lancet.

[41]  R. Benediktsson,et al.  Glucocorticoid exposure in utero: new model for adult hypertension , 1993, The Lancet.

[42]  P. Gluckman,et al.  Chronic Maternal Undernutrition in the Rat Leads to Delayed Postnatal Growth and Elevated Blood Pressure of Offspring , 1996, Pediatric Research.

[43]  J. Reinisch,et al.  Prenatal exposure to prednisone in humans and animals retards intrauterine growth , 1978 .

[44]  M. Hanson,et al.  Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development , 1999, The Journal of physiology.

[45]  G. Osol,et al.  Pregnancy augments uteroplacental vascular endothelial growth factor gene expression and vasodilator effects. , 1997, The American journal of physiology.

[46]  Stephen G Matthews,et al.  Maternal nutrient restriction (48 h) modifies brain corticosteroid receptor expression and endocrine function in the fetal guinea pig , 1999, Brain Research.

[47]  M. J. Dauncey,et al.  Transcriptional Regulation of Insulin-like Growth Factor-II Gene Expression by Cortisol in Fetal Sheep during Late Gestation* , 1998, The Journal of Biological Chemistry.

[48]  P. Clark.  Programming of the hypothalamo-pituitary-adrenal axis and the fetal origins of adult disease hypothesis , 1998, European Journal of Pediatrics.

[49]  C Osmond,et al.  Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. , 2000, Hypertension.

[50]  M. Hanson,et al.  Maternal Undernutrition in Early Gestation Alters Molecular Regulation of the Hypothalamic‐Pituitary‐Adrenal Axis in the Ovine Fetus , 2001, Journal of neuroendocrinology.

[51]  L. Poston,et al.  Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep. , 2000, American journal of obstetrics and gynecology.

[52]  L. Schell,et al.  Environmental noise and human prenatal growth. , 1981, American journal of physical anthropology.

[53]  M A Hanson,et al.  Animal models and programming of the metabolic syndrome. , 2001, British medical bulletin.

[54]  J. Newnham,et al.  Repeated antenatal corticosteroids: size at birth and subsequent development. , 1999, American journal of obstetrics and gynecology.

[55]  J. Seckl,et al.  Distinct Ontogeny of Glucocorticoid and Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Types I and II mRNAs in the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid Actions , 1998, The Journal of Neuroscience.

[56]  C. Byrne,et al.  Programming other hormones that affect insulin. , 2001, British medical bulletin.

[57]  C. Coe,et al.  Antenatal Steroid Treatment and Adverse Fetal Effects: What Is the Evidence? , 2000, The Journal of the Society for Gynecologic Investigation: JSGI.

[58]  M. Meaney,et al.  Corticosteroid Receptors in the Rat Brain and Pituitary during Development and Hypothalamic-Pituitary-Adrenal Function , 1993 .

[59]  C Osmond,et al.  Maternal nutrition in early and late pregnancy in relation to placental and fetal growth , 1996, BMJ.

[60]  J. Seckl,et al.  Prenatal Stress, Glucocorticoids and the Programming of the Brain , 2001, Journal of neuroendocrinology.

[61]  S. Langley-Evans.  Intrauterine programming of hypertension by glucocorticoids. , 1997, Life sciences.

[62]  J. Shaw,et al.  Global and societal implications of the diabetes epidemic , 2001, Nature.

[63]  D. Barker.  The malnourished baby and infant Relationship with Type 2 diabetes , 2001 .

[64]  S. Matthews.  Antenatal glucocorticoids and the developing brain: mechanisms of action. , 2001, Seminars in neonatology : SN.

[65]  S. Matthews.  Antenatal Glucocorticoids and Programming of the Developing CNS , 2000, Pediatric Research.

[66]  H. Budge,et al.  Maternal Undernutrition during Early to Midgestation Programs Tissue-Specific Alterations in the Expression of the Glucocorticoid Receptor, 11β-Hydroxysteroid Dehydrogenase Isoforms, and Type 1 Angiotensin II Receptor in Neonatal Sheep* , 2001 .