PTSD pp 113-135 | Cite as

Tissue Metabolism of Glucocorticoids: New Controls of Cognitive Function and the Stress Response

  • Jonathan R. Seckl


Glucocorticoid Receptor Mineralocorticoid Receptor Prenatal Stress Glycyrrhetinic Acid Dehydrogenase Type 
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  1. Agarwal AK et al. (1989) Cloning and expression of rat cDNA encoding corticosteroid 11 dehydrogenase. J Biol Chem 264:18939–18943PubMedGoogle Scholar
  2. Ajilore OA, Sapolsky RM (1999) In vivo characterization of 11 beta-hydroxysteroid dehydrogenase in rat hippocampus using glucocorticoid neuroendangerment as an endpoint. Neuroendocrinology 69:138–144PubMedCrossRefGoogle Scholar
  3. Alberts P et al. (2002) Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice. Diabetologia 45:1528–1532PubMedCrossRefGoogle Scholar
  4. Albiston AL et al. (1994) Cloning and tissue distribution of the human 11 β-hydroxys-teroid dehydrogenase type 2 enzyme. Mol Cell Endo 105:R11–R17.CrossRefGoogle Scholar
  5. Amelung D et al. (1953) Conversion of cortisone to compound F. J Clin Endocrinol Metab 13:125.Google Scholar
  6. Andrews RC, Rooyackers O, Walker BR (2003) Effects of the 11 beta-hydroxysteroid dehydrogrenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. J Clin Endocrinol Metab 88:285–291PubMedCrossRefGoogle Scholar
  7. Arai Y, Gorski RA (1968) Critical exposure time for androgenization of the developing hypothalamus in the female rat. Endocrinology 82:1010–1014PubMedGoogle Scholar
  8. Barf T et al. (2002) Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs. Discovery of potent and selective inhibitors of the 11 beta-hydroxysteroid dehydrogenase type 1. J Med Chem 45:3813–3815PubMedCrossRefGoogle Scholar
  9. Barker DJP (1994) Mothers, babies and disease in later life. BMJ Publishing Group, London, p 180Google Scholar
  10. Beitens IZ et al. (1973) The metabolic clearance rate, blood production, interconversion and transplacental passage of cortisol and cortisone in pregnancy near term. Pediatr Res 7:509–519Google Scholar
  11. Benediktsson R et al. (1993) Glucocorticoid exposure in utero: a new model for adult hypertension. Lancet 341:339–341PubMedCrossRefGoogle Scholar
  12. Benediktsson R et al. (1995) Fetal osteocalcin levels are related to placental 11β-hydroxysteroid dehydrogenase activity. Clin Endocrinol 42:551–555Google Scholar
  13. Benediktsson R et al. (1997) Placental 11β-hydroxysteroid dehydrogenase type 2 is the placental barrier to maternal glucocorticoids: ex vivo studies. Clin Endocrinol 46:161–166CrossRefGoogle Scholar
  14. Bertram C et al. (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142:2841–2853PubMedCrossRefGoogle Scholar
  15. Bohn MC, Lauder JM (1978) The effects of neonatal hydrocortisone on rat cerebellar development: an autoradiographic and light microscopic study. Dev Neurosci 1:250–266Google Scholar
  16. Bohn MC, Lauder JM (1980) Cerebellar granule cell genesis in hydrocortisone-treated rat. Dev Neurosci 3:81–89PubMedGoogle Scholar
  17. Brown RW et al. (1993) Human placental 11β-hydroxysteroid dehydrogenase: partial purification of and evidence for a distinct NAD-dependent isoform. Endocrinology 132:2614–2621PubMedCrossRefGoogle Scholar
  18. Brown RW et al. (1996a) The ontogeny of 11β-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinology 137:794–797PubMedCrossRefGoogle Scholar
  19. Brown RW et al. (1996b) Isolation and cloning of human placental 11β-hydroxysteroid dehydrogenase-2 cDNA. Biochem J 313:1007–1017PubMedGoogle Scholar
  20. Bujalska I, Kumar S, Stewart PM (1997) Central obesity: “Cushing’s disease of the omentum”. Lancet 349:1210–1213PubMedCrossRefGoogle Scholar
  21. Catalani A et al. (1993) Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance. Brain Res 624:209–215PubMedCrossRefGoogle Scholar
  22. Clark PM et al. (1996) Size at birth and adrenocortical function in childhood. Clin Endocrinol 45:721–726CrossRefGoogle Scholar
  23. Cleasby ME et al. (2003) Programming of rat muscle and fat metabolism by in utero overexposure to glucocorticoids. Endocrinology 144:999–1007PubMedCrossRefGoogle Scholar
  24. Cole TJ et al. (1995) Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell-development and severely retards lung maturation. Genes Dev 9:1608–1621PubMedCrossRefGoogle Scholar
  25. Cratty MS et al. (1995) Prenatal stress increases corticotropin-releasing factor (Crf) content and release in rat amygdala minces. Brain Res 675:297–302PubMedCrossRefGoogle Scholar
  26. Dave-Sharma S et al. (1998) Extensive personal experience — examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab 83:2244–2254PubMedCrossRefGoogle Scholar
  27. Dean F, Matthews S (1999) Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain. Brain Res 846:253–259PubMedCrossRefGoogle Scholar
  28. Diaz R et al. (1995) Prenatal corticosterone increases spontaneous and d-amphetamine induced locomotor activity and brain dopamine metabolism in prepubertal male and female rats. Neuroscience 66:467–473PubMedCrossRefGoogle Scholar
  29. Diaz R, Brown RW, Seckl JR (1996) Corticosteroid receptors and 11β-hydroxyster-oid dehydrogenases; crucial regulators of glucocorticoid action during fetal brain development. In Grauer E, Ben-Nathan D, Levy A (Eds) Proceedings 40th Oholo Conference.Google Scholar
  30. Diaz R, Fuxe K, Ogren SO (1997) Prenatal corticosterone treatment induces long-term changes in spontaneous and apomorphine-mediated motor activity in male and female rats. Neuroscience 81:129–140PubMedCrossRefGoogle Scholar
  31. Diaz R, Brown RW, Seckl JR (1998) Ontogeny of mRNAs encoding glucocorticoid and mineralocorticoid receptors and 11β-hydroxysteroid dehydrogenases in prenatal rat brain development reveal complex control of glucocorticoid action. J Neurosci 18:2570–2580PubMedGoogle Scholar
  32. Dodic M et al. (2002) No evidence for HPA reset in adult sheep with high blood pressure due to short prenatal exposure to dexamethasone. Am J Physiol Regul Integr Comp Physiol 282:R343–R350PubMedGoogle Scholar
  33. Doyle LW et al. (2000) Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children. Clin Sci 98:137–142PubMedCrossRefGoogle Scholar
  34. Draper N et al. (2003) Mutations in the genes encoding 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. Nat Genet 34:434–439PubMedCrossRefGoogle Scholar
  35. Duperrex H et al. (1993) Rat liver 11β-hydoxysteroid dehydrogenase cDNA encodes oxoreductase activity in a mineralocorticoid-responsive toad bladder cell line. Endocrinology 132:612–619PubMedCrossRefGoogle Scholar
  36. Edwards CRW et al. (1993) Dysfunction of the placental glucocorticoid barrier: a link between the foetal environment and adult hypertension? Lancet 341:355–357PubMedCrossRefGoogle Scholar
  37. Encio IJ, Detera-Wadleigh SD (1991) The genomic structure of the human glucocorticoid receptor. J Biol Chem 266:7182–7188PubMedGoogle Scholar
  38. Feldman S, Weidenfeld J (1998) The excitatory effects of the amygdala on hypothalamo-pituitary-adrenocortical responses are mediated by hypothalamic norepinephrine, serotonin, and CRF-41. Brain Res Bull 45:389–393PubMedCrossRefGoogle Scholar
  39. French NP et al. (1998) Repeated antenatal corticosteroids: behaviour outcomes in a regional population of very preterm infants. Pediatr Res 43:214A (Abstract no. 1252)CrossRefGoogle Scholar
  40. French NP et al. (1999) Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol 180:114–121PubMedCrossRefGoogle Scholar
  41. Frye CA et al. (2004) Progesterone enhances motor, anxiolytic, analgesic, and anti-depressive behavior of wild-type mice, but not those deficient in type 1 5 alpha-reductase. Brain Res 1004:116–124PubMedCrossRefGoogle Scholar
  42. Fumagalli F et al. (1996) Expression of mRNA coding for the serotonin transporter in aged vs. young rat brain: differential effects of glucocorticoids. Brain Res 719:225–228PubMedCrossRefGoogle Scholar
  43. Fuxe K et al. (1985) Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel-and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor. Endocrinology 117:1803–1812PubMedGoogle Scholar
  44. Gomez-Sanchez EP (1986) Intracerebroventricular infusion of aldosterone induces hypertension in rats. Endocrinology 118:819–823PubMedGoogle Scholar
  45. Gomez-Sanchez EP, Gomez-Sanchez CE (1992) Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Am J Physiol 263:E1125–E1130PubMedGoogle Scholar
  46. Gomez-Sanchez EP, Fort CM, Thwaites D (1990) Icv infusion of corticosterone antagonises icv-aldosterone hypertension. Am J Physiol XX:E649–E653Google Scholar
  47. Grosser BI (1966) 11β-hydroxysteroid metabolism by mouse brain and glioma 261. J Neurochem 13:475–478PubMedCrossRefGoogle Scholar
  48. Grosser BI, Axelrod LR (1968) Conversion of cortisol to cortisol acetate, cortisone acetate and cortisone by the developing primate brain. Steroids 11:827–836PubMedCrossRefGoogle Scholar
  49. Harris HJ et al. (2001) 11β-hydroxysteroid dehydrogenase type 1 null mice have altered hypothalamic-pituitary-adrenal axis activity: a novel control of glucocorticoid feedback. Endocrinology 142:114–120PubMedCrossRefGoogle Scholar
  50. Hawkins P et al. (2000) Cardiovascular and hypothalamic-pituitary-adrenal axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation. Reprod Fertil Dev 12:443–456PubMedCrossRefGoogle Scholar
  51. Holmes MC, Welberg LA, Seckl JR (2002) Early life programming of the brain by glucocorticoids. 5th International Congress of Neuroendocrinology, Bristol, UK. September 2002, p S57Google Scholar
  52. Huang WL et al. (1999) Effect of corticosteroids on brain growth in fetal sheep. Obstet Gynecol 94:213–218PubMedCrossRefGoogle Scholar
  53. Huang WL et al. (2001a) Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep. Int J Dev Neurosci 19:487–493PubMedCrossRefGoogle Scholar
  54. Huang WL et al. (2001b) Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep. Int J Dev Neurosci 19:415–425PubMedCrossRefGoogle Scholar
  55. Hundertmark S et al. (1995) Correlation of surfactant phosphatidylcholine synthesis and 11beta-hydroxysteroid dehydrogenase in the fetal lung. Endocrinology 136:2573–2578PubMedCrossRefGoogle Scholar
  56. Jamieson A et al. (1999) Apparent cortisone reductase deficiency: a functional defect in 11β-hydroxysteroid dehydrogenase type 1. J Clin Endocrinol Metab 84:3570–3574PubMedCrossRefGoogle Scholar
  57. Jamieson PM et al. (1995) 11β-hydroxysteroid dehydrogenase is an exclusive 11β-reductase in primary cultured rat hepatocytes: effect of physicochemical and hormonal manipulations. Endocrinology 136:4754–4761PubMedCrossRefGoogle Scholar
  58. Jamieson PM, Fuchs E, Seckl J (1997) Chronic psycho-social stress attenuates 11β-hydroxysteroid dehydrogenase activity in the hippocampus and liver in the tree-shrew. Stress 2:123–132PubMedCrossRefGoogle Scholar
  59. Jamieson PM, Chapman KE, Seckl JR (1999) Tissue-and temporal-specific regulation of 11β-hydroxysteroid dehydrogenase type 1 by glucocorticoids in vivo. J Steroid Biochem Mol Biol 68:245–250PubMedCrossRefGoogle Scholar
  60. Jamieson PM et al. (2000) 11β-hydroxysteroid dehydrogenase type 1 is a predominant 11β-reductase in the intact perfused rat liver. J Endocrinol 165:685–692PubMedCrossRefGoogle Scholar
  61. Jenkins BD, Pullen CB, Darimont BD (2001) Novel glucocorticoid receptor coactivator effector mechanisms. Trends Endocrinol Metab 12:122–126PubMedCrossRefGoogle Scholar
  62. Johnstone HA et al. (2000) Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late pregnancy: changes in feedforward and feedback mechanisms. J Neuroendocrinol 12:811–822PubMedCrossRefGoogle Scholar
  63. Kitraki E, Kittas C, Stylianopoulou F (1997) Glucocorticoid receptor gene expression during rat embryogenesis. An in situ hybridization study. Differentiation 62:21–31PubMedCrossRefGoogle Scholar
  64. Klemcke HG (1995) Placental metabolism of cortisol at mid-and late gestation in swine. Biol Reprod 53:1293–1301PubMedCrossRefGoogle Scholar
  65. de Kloet ER (1991) Brain corticosteroid receptor balance and homeostatic control. Front Neuroendocrinol 12:95–164Google Scholar
  66. de Kloet ER (2004) Hormones and the stressed brain. Stress: Current Neuroendocrine and Genetic Approaches XX: 1–15Google Scholar
  67. de Kloet ER, Wallach G, McEwen BS (1975) Differences in corticosterone and dexamethasone binding to rat brain and pituitary. Endocrinology 96:598–609PubMedGoogle Scholar
  68. Koenig JI, Kirkpatrick B, Lee P (2002) Glucocorticoid hormones and early brain development in schizophrenia. Neuropsychopharmacology 27:309–318PubMedCrossRefGoogle Scholar
  69. Korte SM (2001) Corticosteroids in relation to fear, anxiety and psychopathology. Neurosci Biobehav Rev 25:117–142PubMedCrossRefGoogle Scholar
  70. Kotelevtsev Y et al. (1997) 11β-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid inducible responses and resist hyperglycaemia on obesity or stress. Proc Natl Acad Sci USA 94:14924–14929PubMedCrossRefGoogle Scholar
  71. Kotelevtsev Y et al. (1999) Hypertension in mice lacking 11β-hydroxysteroid dehydrogenase type 2. J Clin Invest 103:683–689PubMedGoogle Scholar
  72. Lakshmi V, Monder C (1988) Purification and characterisation of the corticosteroid 11β-dehydrogenase component of the rat liver 11β-hydroxysteroid dehydrogenase complex. Endocrinology 123:2390–2398PubMedGoogle Scholar
  73. Lakshmi V et al. (1991) Regional distribution of 11β-hydroxysteroid dehydrogenase in rat brain. Endocrinology 128:1741–1748PubMedGoogle Scholar
  74. Landfield PW, Waymire J, Lynch G (1978) Hippocampal aging and adrenocorticoids: a quantitative correlation. Science 202:1098–1102PubMedCrossRefGoogle Scholar
  75. Langley-Evans SC (1997) Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis. J Hypertens 15:537–544PubMedCrossRefGoogle Scholar
  76. Langley-Evans SC, Gardner DS, Jackson AA (1996a) Maternal protein restriction influences the programming of the rat hypothalamic-pituitary-adrenal axis. J Nutr 126:1578–1585PubMedGoogle Scholar
  77. Langley-Evans SC et al. (1996b) Maternal dietary protein restriction, placental glucocorticoid metabolism and the programming of hypertension. Placenta 17:169–172PubMedCrossRefGoogle Scholar
  78. Levine S (1957) Infantile experience and resistance to physiological stress. Science 126:405–406PubMedCrossRefGoogle Scholar
  79. Levine S (1962) Plasma-free corticosteroid response to electric shock in rats stimulated in infancy. Science 135:795–796PubMedCrossRefGoogle Scholar
  80. Levitt NS et al. (1996) Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. Neuroendocrinology 64:412–418PubMedGoogle Scholar
  81. Levitt NS et al. (2000) Impaired glucose tolerance and elevated blood pressure in low birth weight, non-obese young South African adults: early programming of the cortisol axis. J Clin Endocrinol Metab 85:4611–4618PubMedCrossRefGoogle Scholar
  82. Lindsay RS et al. (1996a) Inhibition of 11β-hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring. Hypertension 27:1200–1204PubMedGoogle Scholar
  83. Lindsay RS et al. (1996b) Programming of glucose tolerance in the rat: role of placental 11β-hydroxysteroid dehydrogenase. Diabetologia 39:1299–1305PubMedCrossRefGoogle Scholar
  84. Liu D et al. (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277:1659–1662PubMedCrossRefGoogle Scholar
  85. Low SC et al. (1994a) Liver-type 11β-hydroxysteroid dehydrogenase cDNA encodes reductase not dehydrogenase activity in intact mammalian COS-7 cells. J Mol Endocrinol 13:167–174PubMedGoogle Scholar
  86. Low SC et al. (1994b) Glucocorticoids and chronic stress up-regulate 11β-hydroxysteroid dehydrogenase activity and gene expression in the hippocampus. J Neuroendocrinol 6:285–290PubMedCrossRefGoogle Scholar
  87. MacArthur BA et al. (1982) School progress and cognitive development of 6-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 70:99–105PubMedGoogle Scholar
  88. Maccari S et al. (1995) Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress. J Neurosci 15:110–116PubMedGoogle Scholar
  89. McCormick J et al. (2000) 5′-heterogeneity of glucocorticoid receptor mRNA is tissue-specific; differential regulation of variant promoters by early life events. Mol Endocrinol 14:506–517PubMedCrossRefGoogle Scholar
  90. McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22:105–122PubMedCrossRefGoogle Scholar
  91. McEwen BS (2003) Mood disorders and allostatic load. Biol Psychiatry 54:200–207PubMedCrossRefGoogle Scholar
  92. McEwen BS et al. (1986) Aldosterone effects on salt appetite in adrenalectomised rats. Neuroendocrinology 43:38–43PubMedGoogle Scholar
  93. McInnes KJ et al. (2004) 5 alpha-reduced glucocorticoids, novel endogenous activators of the glucocorticoid receptor. J Biol Chem 279:22908–22912PubMedCrossRefGoogle Scholar
  94. McMullen S et al. (2004) Alterations in placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activities and fetal cortisol: cortisone ratios induced by nutritional restriction prior to conception and at defined stages of gestation in ewes. Reproduction 127:717–725PubMedCrossRefGoogle Scholar
  95. McTernan CL et al. (2001) Reduced placental 11 beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms. J Clin Endocrinol Metab 86:4979–4983PubMedCrossRefGoogle Scholar
  96. Mahendroo M et al. (1997) Fetal death in mice lacking 5alpha-reductase type 1 caused by estrogen excess. Mol Endocrinol 11:917–927PubMedCrossRefGoogle Scholar
  97. Masuzaki H et al. (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170PubMedCrossRefGoogle Scholar
  98. Masuzaki H et al. (2003) Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. J Clin Invest 112:83–90PubMedCrossRefGoogle Scholar
  99. Matthews SG (1998) Dynamic changes in glucocorticoid and mineralocorticoid receptor mRNA in the developing guinea pig brain. Brain Res Dev Brain Res 107:123–132PubMedCrossRefGoogle Scholar
  100. Matthews SG (2002) Early programming of the hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab 130:373–380Google Scholar
  101. Mattsson C et al. (2003) Reduced mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 1 expression in hippocampus of Zucker fat rats; mechanisms for altered feedback control of the hypothalamic-pituitary-adrenal axis in obesity. Endocrinology (in press).Google Scholar
  102. Meaney MJ et al. (1988) Effect of neonatal handling on age-related impairments associated with the hippocampus. Science 239:766–768PubMedCrossRefGoogle Scholar
  103. Meaney MJ et al. (1989) Neonatal handling alters adrenocortical negative feedback sensitivity and hippocampal type II glucocorticoid receptor binding in the rat. Neuroendocrinology 50:597–604PubMedGoogle Scholar
  104. Meaney MJ et al. (1992) Basal ACTH, corticosterone and corticosterone-binding globulin levels over the diurnal cycle, and hippocampal corticosteroid receptors in young and aged, handled and non-handled rats. Neuroendocrinology 55:204–213PubMedGoogle Scholar
  105. Meaney MJ et al. (1995) Individual differences in hypothalamic-pituitary-adrenal activity in later life and hippocampal aging. Exp Gerontol 30:229–251PubMedCrossRefGoogle Scholar
  106. Meaney MJ et al. (1996) Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev Neurosci 18:49–72PubMedGoogle Scholar
  107. Meaney MJ et al. (2000) Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: the effects of thyroid hormones and serotonin. J Neurosci 20:3926–3935PubMedGoogle Scholar
  108. Meyer JS (1983) Early adrenalectomy stimulates subsequent growth and development of the rat brain. Exp Neurol 82:432–446PubMedCrossRefGoogle Scholar
  109. Mitchell JB et al. (1990) Serotonin regulates type II corticosteroid receptor binding in hippocampal cell cultures. J Neurosci 10:1745–1752PubMedGoogle Scholar
  110. Miyabo S, Kishida S, Hisada T (1973) Metabolism and conjugation of cortisol by various dog tissues in vitro. J Steroid Biochem 4:567–576PubMedCrossRefGoogle Scholar
  111. Moisan M-P et al. (1990) 11β-hydroxysteroid dehydrogenase messenger ribonuceic acid expression, bioactivity and immunoreactivity in rat cerebellum. J Neuroendocrinol 2:853–858CrossRefPubMedGoogle Scholar
  112. Moisan M-P, Seckl JR, Edwards CRW (1990) 11β-hydroxysteroid dehydrogenase bioactivity and messenger RNA expression in rat forebrain: localization in hypothalamus, hippocampus and cortex. Endocrinology 127:1450–1455PubMedGoogle Scholar
  113. Morton NM et al. (2001) Improved lipid and lipoprotein profile, hepatic insulin sensitivity and glucose tolerance in 11 beta-hydroxysteroid dehydrogenase type 1 null mice. J Biol Chem 276:41293–41300PubMedCrossRefGoogle Scholar
  114. Mune T et al. (1995) Human hypertension caused by mutations in the kidney isozyme of 11β-hydroxysteroid dehydrogenase. Nat Genet 10:394–399PubMedCrossRefGoogle Scholar
  115. Murphy VE et al. (2002) Reduced 11 beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma. J Clin Endocrinol Metab 87:1660–1668PubMedCrossRefGoogle Scholar
  116. Napolitano A et al. (1998) 11β-hydroxysteroid dehydrogenase type 1 in adipocytes: expression is differentiation-dependent and hormonally-regulated. J Steroid Biochem Mol Biol 64:251–260PubMedCrossRefGoogle Scholar
  117. Nitabach MN, Schulkin J, Epstein A (1989) The medial amygdala is part of a mineralocorticoid-sensitive circuit controlling NaCl ingestion in the rat. Behav Brain Res 35:159–161CrossRefGoogle Scholar
  118. Nyirenda MJ et al. (1998) Glucocorticoid exposure in late gestation permanently programmes rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring. J Clin Invest 101:2174–2181PubMedGoogle Scholar
  119. Ozols J (1995) Lumenal orientation and post-translational modification of the liver microsomal 11β-hydroxysteroid dehydrogenase. J Biol Chem 270:2305–2312PubMedGoogle Scholar
  120. Paterson J et al. (2004) Metabolic syndrome without obesity: hepatic over-expression of 11β-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proc Natl Acad Sci USA 101:7088–7093PubMedCrossRefGoogle Scholar
  121. Peterson NA, Chaikoff IL, Jones C (1965) The in vitro conversion of cortisol to cortisone by subcellular brain fractions of young and adult rats. J Neurochem 12:273–278PubMedCrossRefGoogle Scholar
  122. Phillipou G, Palermo M, Shackleton C (1996) Apparent cortisone reductase deficiency; a unique form of hypercortisolism. J Clin Endocrinol Metab 81:3855–3860CrossRefGoogle Scholar
  123. Phillips DIW et al. (1998) Elevated plasma cortisol concentrations: an explanation for the relationship between low birthweight and adult cardiovascular risk factors. J Clin Endocrinol Metab 83:757–760PubMedCrossRefGoogle Scholar
  124. Phillips DIW et al. (2000) Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. Hypertension 35:1301–1306PubMedGoogle Scholar
  125. de Quervain DJF et al. (2004) Glucocorticoid-related genetic susceptibility for Alzheimer’s disease. Hum Mol Genet 13:47–52PubMedCrossRefGoogle Scholar
  126. Rajan V, Edwards CRW, Seckl JR (1996) 11β-hydroxysteroid dehydrogenase in cultured hippocampal cells reactivates inert 11-dehydrocorticosterone, potentiating neurotoxicity. J Neurosci 16:65–70PubMedGoogle Scholar
  127. Reynolds RM et al. (2001) Altered control of cortisol secretion in adult men with low birth weight and cardiovascular risk factors. J Clin Endocrinol Metab 86:245–250PubMedCrossRefGoogle Scholar
  128. Reznikov AG, Nosenko ND, Tarasenko LV (2004) Early postnatal effects of prenatal exposure to glucocorticoids on testosterone metabolism and biogenic monoamines in discrete neuroendocrine regions of the rat brain. Comp Biochem Physiol C Toxicol Pharmacol 138:169–175PubMedCrossRefGoogle Scholar
  129. Robson AC et al. (1998) Expression of 11β-hydroxysteroid dehydrogenase type 2 in the postnatal and adult rat brain. Mol Brain Res 61:1–10PubMedCrossRefGoogle Scholar
  130. Rogerson FM, Kayes K, White PC (1996) No correlation in human placenta between activity or mRNA for the K (type 2) isozyme of 11β-hydroxysteroid dehydrogenase and fetal or placental weight. Tenth International Congress of Endocrinology Abstracts Pl-231:193Google Scholar
  131. Rogerson FM, Kayes KM, White PC (1997) Variation in placental type 2 11beta-hydroxysteroid dehydrogenase activity is not related to birth weight or placental weight. Mol Cell Endocrinol 128:103–109PubMedCrossRefGoogle Scholar
  132. Roland BL, Li KXZ, Funder JW (1995) Hybridization histochemical localization of 11β-hydroxysteroid dehydrogenase type 2 in rat brain. Endocrinology 136:4697–4700PubMedCrossRefGoogle Scholar
  133. Sakai RR et al. (1990) Colocalization of 11β-hydroxysteroid dehydrogenase and mineralocorticoid receptor in rat brain. Soc Neurosci Abstr XX:7773Google Scholar
  134. Sakai RR et al. (1992) Immunocytochemical localisation of 11beta-hydroxysteroid dehydrogenase in hippocampus and other brain regions of the rat. J Neuroendocrinol 4:101–106CrossRefGoogle Scholar
  135. Sandeep T et al. (2004) Effects of 11beta-hydroxysteroid dehydrogenase inhibition on cognitive function in healthy elderly men and patients with type 2 diabetes. Proc Natl Acad Sci USA 101:6734–6739PubMedCrossRefGoogle Scholar
  136. Seckl JR (1997) 11β-hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action? Front Neuroendocrinol 18:49–99PubMedCrossRefGoogle Scholar
  137. Seckl JR (2004a) 11β-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 4:597–602PubMedCrossRefGoogle Scholar
  138. Seckl JR (2004b) Prenatal glucocorticoids and long-term programming. Eur J Endocrinol 151:U49–U62PubMedCrossRefGoogle Scholar
  139. Seckl JR, Walker BR (2001) 11β-hydroxysteroid dehydrogenase type 1: a tissue-specific amplifier of glucocorticoid action. Endocrinology 142:1371–1376PubMedCrossRefGoogle Scholar
  140. Seckl JR, Walker BR (2004) 11beta-hydroxysteroid dehydrogenase type 1 as a modulator of glucocorticoid action: from metabolism to memory. Trends Endocrinol Metab 15:418–424PubMedCrossRefGoogle Scholar
  141. Seckl JR, Kelly PAT, Sharkey J (1991) Glycyrrhetinic acid, an inhibitor of 11β-hydroxysteroid dehydrogenase, alters local cerebral glucose utilization in vivo. J Steroid Biochem Mol Biol 39:777–779PubMedCrossRefGoogle Scholar
  142. Seckl JR et al. (1993) The 11β-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides. J Endocrinol 136:471–477PubMedCrossRefGoogle Scholar
  143. Seckl JR et al. (2004) Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue. Recent Prog Horm Res XX:359–393CrossRefGoogle Scholar
  144. Shams M et al. (1998) 11beta hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth retardation. Hum Reprod 13:799–804PubMedCrossRefGoogle Scholar
  145. Sholiton LJ, Werk EE Jr, MacGee J (1965) Metabolism of cortisol-4-14C and cortisone-4-14C by rat brain homogenates. Metab Clin Exp 14:1122–1127PubMedGoogle Scholar
  146. Sloboda DM et al. (2002) The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function. J Endocrinol 172:71–81PubMedCrossRefGoogle Scholar
  147. Slotkin TA et al. (1996) Programming of brainstem serotonin transporter development by prenatal glucocorticoids. Dev Brain Res 93:155–161CrossRefGoogle Scholar
  148. Sloviter RS et al. (1989) Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science 243:535–538PubMedCrossRefGoogle Scholar
  149. Smythe JW, Rowe WB, Meaney MJ (1994) Neonatal handling alters serotonin (5-HT) turnover and 5-HT2 receptor binding in selected brain regions: relationship to the handling effect on glucocorticoid receptor expression. Dev Brain Res 80:183–189CrossRefGoogle Scholar
  150. Stewart PM, Krozowski ZS (1999) 11 beta-hydroxysteroid dehydrogenase. Vitam Horm 57:249–324PubMedGoogle Scholar
  151. Stewart PM et al. (1987) Mineralocorticoid activity of liquorice: 11β-hydroxysteroid dehydrogenase deficiency comes of age. Lancet ii:821–824CrossRefGoogle Scholar
  152. Stewart PM et al. (1990) Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11β-hydroxysteroid dehydrogenase activity in man. Clin Sci 78:49–54PubMedGoogle Scholar
  153. Stewart PM, Murry BA, Mason JI (1994) Type 2 11β-hydroxysteroid dehydrogenase in human fetal tissues. J Clin Endocrinol Metab 78:1529–1532PubMedCrossRefGoogle Scholar
  154. Stewart PM, Rogerson FM, Mason JI (1995) Type 2 11β-hydroxysteroid dehydrogenase messenger RNA and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal steroidogenesis. J Clin Endocrinol Metab 80:885–890PubMedCrossRefGoogle Scholar
  155. Thigpen AE et al. (1993) Tissue distribution and ontogeny of steroid 5-alpha-reduc-tase isozyme expression. J Clin Invest 92:903–910PubMedGoogle Scholar
  156. Thomassin H et al. (2001) Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J 20:1974–1983PubMedCrossRefGoogle Scholar
  157. Torres JM, Ortega E (2003) Differential regulation of steroid 5 alpha-reductase isozymes expression by androgens in the adult rat brain. FASEB J 17:1428–1433PubMedCrossRefGoogle Scholar
  158. Trautman PD et al. (1995) Effects of early prenatal dexamethasone on the cognitive and behavioral development of young children: results of a pilot study. Psychoneuroendocrinology 20:439–449PubMedCrossRefGoogle Scholar
  159. Tronche F et al. (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23:99–103PubMedCrossRefGoogle Scholar
  160. Ulick S et al. (1979) A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol. J Clin Endocrinol Metab 49:757–764PubMedCrossRefGoogle Scholar
  161. Venihaki MA et al. (2000) Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency. Proc Natl Acad Sci USA 97:7336–7341PubMedCrossRefGoogle Scholar
  162. Vreugdenhil E, de Kloet ER (1998) Corticosteroid hormones and neuronal vulnerability: towards identification of candidate vulnerability genes. Prog Brain Res 117:9–22PubMedCrossRefGoogle Scholar
  163. Walker BR et al. (1992) Mineralocorticoid excess and inhibition of 11β-hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome. Clin Endocrinol 37:483–492Google Scholar
  164. Walker BR et al. (1995) Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J Clin Endocrinol Metab 80:3155–3159PubMedCrossRefGoogle Scholar
  165. Weaver I et al. (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854PubMedCrossRefGoogle Scholar
  166. Weinstock M (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65:427–451PubMedCrossRefGoogle Scholar
  167. Welberg LAM, Seckl JR (2001) Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 13:113–128PubMedCrossRefGoogle Scholar
  168. Welberg LAM, Seckl JR, Holmes MC (2000) Inhibition of 11β-hydroxysteroid dehydrogenase, the feto-placental barrier to maternal glucocorticoids, permanently programs amygdala glucocorticoid receptor mRNA expression and anxiety-like behavior in the offspring. Eur J Neurosci 12:1047–1054PubMedCrossRefGoogle Scholar
  169. Welberg LAM, Seckl JR, Holmes MC (2001) Prenatal glucocorticoid programming of brain corticosteroid receptors and corticotrophin-releasing hormone: possible implications for behaviour. Neuroscience 104:71–79PubMedCrossRefGoogle Scholar
  170. Yau JLW, Noble J, Seckl JR (1997a) Site-specific regulation of corticosteroid and serotonin receptor subtype gene expression in the rat hippocampus following methylenedioxymethamphetamine: role of corticosterone and serotonin. Neuroscience 78:111–121PubMedCrossRefGoogle Scholar
  171. Yau JLW et al. (1997b) Impact of adrenalectomy on 5-HT6 and 5-HT7 receptor gene expression in the rat hippocampus. Mol Brain Res 45:182–186PubMedCrossRefGoogle Scholar
  172. Yau JLW et al. (2001) Lack of tissue glucocorticoid reactivation in 11β-hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments. Proc Natl Acad Sci USA 98:4716–4721PubMedCrossRefGoogle Scholar
  173. Yeh T et al. (2004) Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 350:1304–1313PubMedCrossRefGoogle Scholar
  174. Yongue BG, Roy EJ (1987) Endogenous aldosterone and corticosterone in brain cell nuclei of adrenal-intact rats: regional distribution and effects of physiological variations in serum steroids. Brain Res 436:49–61PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 2006

Authors and Affiliations

  • Jonathan R. Seckl
    • 1
  1. 1.Endocrinology UnitQueen’s Medical Research InstituteEdinburghUK

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