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Nick Hales Award Lecture 2011: glucocorticoids and early life programming of cardiometabolic disease

Published online by Cambridge University Press:  18 May 2012

R. M. Reynolds
R. M. Reynolds*
Affiliation:
Reader in Endocrinology and Diabetes, Endocrinology Unit, Queen's Medical Research Institute, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
*
*Address for correspondence: R. M. Reynolds, Reader in Endocrinology and Diabetes, Endocrinology Unit, Queen's Medical Research Institute, University/BHF Centre for Cardiovascular Science, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. (Email R.Reynolds@ed.ac.uk)
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Abstract

Epidemiological studies have demonstrated an association between low birthweight and a range of diseases in adult life including cardiometabolic and psychiatric diseases. One of the key mechanisms proposed to underlie early life ‘programming’ of disease is overexposure of the developing foetus to glucocorticoids. This review will explore the data from human studies that glucocorticoids are not only mediators of programming, but also targets of programming. Cohort studies of men and women of known birthweight have demonstrated that low birthweight is associated with high fasting cortisol levels. In healthy individuals and in people with type 2 diabetes who are at high cardiovascular risk, there is a similar association between high fasting cortisol and the metabolic syndrome. The high cortisol levels appear to be due to activation of the hypothalamic–pituitary–adrenal (HPA) axis though detailed studies to further explore central negative feedback sensitivity are required. The evidence in humans that glucocorticoids mediate programming is more scanty, though changes in maternal body composition, stress and anxiety levels and activity of the placental barrier enzyme 11 β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) may all influence maternal HPA axis activity. Emerging studies are supportive that high maternal cortisol levels in humans and/or deficiencies placental 11β-HSD2 humans are associated with lower birthweight and adverse metabolic and neurocognitive outcomes in the offspring.

Keywords

cardiometabolic diseaseglucocorticoidsprogramming
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 5 , October 2012 , pp. 309 - 314
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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References

1. Barker, DJP. Fetal origins of coronary heart disease. Br Med J. 1995; 311, 171–174.CrossRefGoogle ScholarPubMed
2. Gluckman, PD, Hanson, MA. Living with the past: evolution, development, and patterns of disease. Science. 2004; 305, 1733–1736.CrossRefGoogle ScholarPubMed
3. Seckl, JR. Prenatal glucocorticoids and long-term programming. Eur J Endocrinol. 2004; 151, 49–62.CrossRefGoogle ScholarPubMed
4. Roberts, D, Dalziel, S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006; 3, CD004454.Google Scholar
5. Cleasby, ME, Kelly, PA, Walker, BR, Seckl, JR. Programming of rat muscle and fat metabolism by in utero overexposure to glucocorticoids. Endocrinology. 2003; 144, 999–1007.CrossRefGoogle ScholarPubMed
6. Nyirenda, MJ, Lindsay, RS, Kenyon, CJ, Burchell, A, Seckl, JR. Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring. J Clin Invest. 1998; 101, 2174–2181.CrossRefGoogle ScholarPubMed
7. Welberg, LAM, Seckl, JR, Holmes, MC. Inhibition of 11beta-hydroxysteroid dehydrogenase, the foetoplacental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety-like behaviour in the offspring. Eur J Neurosci. 2000; 12, 1047–1054.CrossRefGoogle ScholarPubMed
8. Phillips, DIW, Barker, DJP, Fall, CHD, et al. . Elevated plasma cortisol concentrations: an explanation for the relationship between low birthweight and adult cardiovascular risk factors. J Clin Endocrinol Metab. 1998; 83, 757–760.Google Scholar
9. Phillips, DIW, Walker, BR, Reynolds, RM, et al. . Low birthweight and elevated plasma cortisol concentrations in adults from three populations. Hypertension. 2000; 35, 1301–1306.CrossRefGoogle Scholar
10. van, MN, Finken, MJ, le, CS, Dekker, FW, Wit, JM. Could cortisol explain the association between birth weight and cardiovascular disease in later life? A meta-analysis. Eur J Endocrinol. 2005; 153, 811–817.Google Scholar
11. Price, JF, Reynolds, RM, Mitchell, RJ, et al. . The Edinburgh Type 2 Diabetes Study: study protocol. BMC Endocr Disord. 2008; 8, 18.CrossRefGoogle ScholarPubMed
12. Reynolds, RM, Labad, J, Strachan, MW, et al. . Elevated fasting plasma cortisol is associated with ischemic heart disease and its risk factors in people with type 2 diabetes: the Edinburgh type 2 diabetes study. J Clin Endocrinol Metab. 2010; 95, 1602–1608.CrossRefGoogle ScholarPubMed
13. Ward, AM, Fall, CH, Stein, CE, et al. . Cortisol and the metabolic syndrome in South Asians. Clin Endocrinol. 2003; 58, 500–505.CrossRefGoogle ScholarPubMed
14. Watt, GCM, Harrap, SB, Foy, CJW, et al. . Abnormalities of glucocorticoid metabolism and the renin–angiotensin system: a four corners approach to the identification of genetic determinants of blood pressure. J Hypertens. 1992; 10, 473–482.CrossRefGoogle Scholar
15. Davey Smith, G, Ben-Shlomo, Y, Beswick, A, et al. . Cortisol, testosterone and coronary heart disease. Prospective evidence from the Caerphilly study. Circulation. 2005; 112, 332–340.CrossRefGoogle Scholar
16. Reynolds, RM, Ilyas, B, Price, JF, et al. . Circulating plasma cortisol concentrations are not associated with coronary artery disease or peripheral vascular disease. QJM. 2009; 102, 469–475.CrossRefGoogle ScholarPubMed
17. Alevizaki, M, Cimponeriu, A, Lekakis, J, Papamichael, C, Chrousos, GP. High anticipatory stress plasma cortisol levels and sensitivity to glucocorticoids predict severity of coronary artery disease in subjects undergoing coronary angiography. Metabolism. 2007; 56, 222–226.CrossRefGoogle ScholarPubMed
18. Kakio, T, Matsumori, A, Ohashi, N, et al. . The effect of hydrocortisone on reducing rates of restenosis and target lesion revascularization after coronary stenting less than 3 mm in stent diameter. Int Med. 2003; 42, 1084–1089.CrossRefGoogle ScholarPubMed
19. Villa, AE, Guzman, LA, Chen, W, et al. . Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty. J Clin Invest. 1994; 93, 1243–1249.CrossRefGoogle Scholar
20. McEwen, BS. Stress and the aging hippocampus. Front Neuroendocrinol. 1999; 20, 49–70.CrossRefGoogle ScholarPubMed
21. Seckl, JR, Dickson, KL, Yates, C, Fink, G. Distribution of glucocorticoid and mineralocorticoid receptor messenger RNA expression in human postmortem hippocampus. Brain Res. 1991; 561, 332–337.CrossRefGoogle ScholarPubMed
22. Meaney, MJ, O'Donnell, D, Rowe, W, et al. . Individual differences in hypothalamic–pituitary–adrenal activity in later life and hippocampal aging. Exp Gerontol. 1995; 30, 229–251.CrossRefGoogle ScholarPubMed
23. Landfield, PW, Baskin, RK, Pitler, TA. Brain aging correlates: retardation by hormonal–pharmacological treatments. Science. 1981; 214, 581–584.CrossRefGoogle ScholarPubMed
24. Vallee, M, Maccari, S, Dellu, F, et al. . Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat. Eur J Neurosci. 1999; 11, 2906–2916.CrossRefGoogle ScholarPubMed
25. MacLullich, AM, Deary, IJ, Starr, JM, et al. . Plasma cortisol levels, brain volumes and cognition in healthy elderly men. Psychoneuroendocrinology. 2005; 30, 505–515.CrossRefGoogle ScholarPubMed
26. Wolf, OT, Convit, A, de Leon, MJ, Caraos, C, Qadri, SF. Basal hypothalamo–pituitary–adrenal axis activity and corticotropin feedback in young and older men: relationships to magnetic resonance imaging-derived hippocampus and cingulate gyrus volumes. Neuroendocrinology. 2002; 75, 241–249.CrossRefGoogle Scholar
27. Reynolds, RM, Strachan, MW, Labad, J, et al. . Morning cortisol levels and cognitive abilities in people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care. 2010; 33, 714–720.CrossRefGoogle ScholarPubMed
28. Finkel, D, Reynolds, CA, McArdle, JJ, Pedersen, NL. Age changes in processing speed as a leading indicator of cognitive aging. Psychol Aging. 2007; 22, 558–568.CrossRefGoogle ScholarPubMed
29. Reynolds, RM, Labad, J, Sears, A, et al. . Glucocorticoid treatment and impaired mood, memory and metabolism in people with type 2 diabetes: the Edinburgh type 2 diabetes study. Eur J Endocrinol. 2012; 166, 861–868.CrossRefGoogle ScholarPubMed
30. Labad, J, Price, JF, Strachan, MW, et al. . Symptoms of depression but not anxiety are associated with central obesity and cardiovascular disease in people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetologia. 2010; 53, 467–471.CrossRefGoogle Scholar
31. Fall, CH, Dennison, E, Cooper, C, et al. . Does birth weight predict adult serum cortisol concentrations? Twenty-four-hour profiles in the United Kingdom 1920–1930 Hertfordshire Birth Cohort. J Clin Endocrinol Metab. 2002; 87, 2001–2007.Google ScholarPubMed
32. Kajantie, E, Eriksson, J, Osmond, C, et al. . Size at birth, the metabolic syndrome and 24-h salivary cortisol profile. Clin Endocrinol. 2004; 60, 201–207.CrossRefGoogle ScholarPubMed
33. Levitt, NS, Lambert, EV, Woods, D, et al. . Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young South African adults: early programming of cortisol axis. J Clin Endocrinol Metab. 2000; 85, 4611–4618.Google ScholarPubMed
34. Reynolds, RM, Walker, BR, Phillips, DIW, et al. . Altered control of cortisol secretion in adult men with low birthweight and cardiovascular risk factors. J Clin Endocrinol Metab. 2001; 86, 245–250.Google ScholarPubMed
35. Reynolds, RM, Godfrey, KM, Barker, M, Osmond, C, Phillips, DI. Stress responsiveness in adult life: influence of mother's diet in late pregnancy. J Clin Endocrinol Metab. 2007; 92, 2208–2210.CrossRefGoogle ScholarPubMed
36. Wust, S, Entringer, S, Federenko, IS, Schlotz, W, Hellhammer, DH. Birth weight is associated with salivary cortisol responses to psychosocial stress in adult life. Psychoneuroendocrinology. 2005; 30, 591–598.CrossRefGoogle ScholarPubMed
37. Meijer, OC, de Lange, ECM, Breimer, DD, et al. . Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdr1A P-glycoprotein knockout mice. Endocrinology. 1998; 139, 1789–1793.CrossRefGoogle ScholarPubMed
38. Mattsson, C, Reynolds, RM, Simonyte, K, Olsson, T, Walker, BR. Combined receptor antagonist stimulation of the HPA axis test identifies impaired negative feedback sensitivity to cortisol in obese men. J Clin Endocrinol Metab. 2009; 94, 1347–1352.CrossRefGoogle ScholarPubMed
39. Jung, C, Ho, JT, Torpy, DJ, et al. . A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum. J Clin Endocrinol Metab. 2011; 96, 1533–1540.CrossRefGoogle ScholarPubMed
40. Entringer, S, Buss, C, Andersen, J, et al. . Ecological momentary assessment of maternal cortisol profiles over a multiple-day period predicts the length of human gestation. Psychosom Med. 2011; 73, 469–474.CrossRefGoogle Scholar
41. Goedhart, G, Vrijkotte, TGM, Roseboom, TJ, et al. . Maternal cortisol and offspring birthweight: results from a large prospective cohort study. Psychoneuroendocrinology. 2010; 35, 644–652.CrossRefGoogle ScholarPubMed
42. Bolten, MI, Wurmser, H, Buske-Kirschbaum, A, et al. . Cortisol levels in pregnancy as a psychobiological predictor for birth weight. Arch Womens Ment Health. 2011; 14, 33–41.CrossRefGoogle ScholarPubMed
43. Yehuda, R, Engel, SM, Brand, SR, et al. . Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. J Clin Endocrinol Metab. 2005; 90, 4115–4118.CrossRefGoogle Scholar
44. Bergman, K, Sarkar, P, Glover, V, et al. . Maternal prenatal cortisol and infant cognitive development: moderation by infant–mother attachment. Biol Psychiatry. 2010; 67, 1026–1032.CrossRefGoogle ScholarPubMed
45. Raikkonen, K, Pesonen, AK, Heinonen, K, et al. . Maternal licorice consumption and detrimental cognitive and psychiatric outcomes in children. Am J Epidemiol. 2009; 170, 1137–1146.CrossRefGoogle ScholarPubMed
46. Van Dijk, AE, Van Eijsden, M, Stronks, K, et al. . The relation of maternal job strain and cortisol levels during early pregnancy with body composition in the 5-year-old child: the ABCD study. Early Hum Dev. 2011; 88, 351–356.CrossRefGoogle ScholarPubMed
47. Clifton, VL. Review: sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta. 2010; 31, S33–S39.CrossRefGoogle ScholarPubMed
48. Marsit, CJ, Maccani, MA, Padbury, JF, et al. . Placental 11-beta hydroxysteroid dehydrogenase methylation is associated with newborn growth and a measure of neurobehavioural outcome. PLoS One. 2012; 7, e33794.CrossRefGoogle Scholar