Abstract
Glucocorticoids (GCs) are essential for many aspects of normal brain development. However, there is growing evidence from a number of species that exposure of the fetal brain to excess GC, at critical stages of development, can have life-long effects on behavior and neuroendocrine function. The hypothalamo-pituitary-adrenal axis, which is central to the integration of the individual's endocrine and behavioral response to stress, appears highly sensitive to excess GC exposure during development. A number of animal studies have shown that exposure to synthetic GCs in utero results in adult offspring that exhibit hyperactivity of the hypothalamo-pituitary-adrenal axis. This will have a long-term impact on health, inasmuch as increased life-long exposure to endogenous GC has been linked to the premature onset of diseases associated with aging. The mechanisms involved in the permanent programming of hypothalamo-pituitary-adrenal function and behavior are not well understood. Synthetic GCs are used extensively to promote pulmonary maturation in fetuses at risk of being delivered before term. Therefore, it is important that we understand the potential long-term consequences of prenatal GC exposure on brain development as well as the underlying mechanisms involved. This review will explore the current state of knowledge in this rapidly expanding field.
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Abbreviations
- AVP:
-
vasopressin
- CRH:
-
corticotropin-releasing hormone
- GC:
-
glucocorticoid
- GR:
-
glucocorticoid receptor
- HPA:
-
hypothalamo-pituitary-adrenal
- MR:
-
mineralocorticoid receptor
- PVN:
-
paraventricular nucleus
- 11β-HSD:
-
11β-hydroxysteroid dehydrogenase
References
Gould E 1994 The effects of adrenal steroids and excitatory input on neuronal birth and survival. Ann NY Acad Sci 743: 73–94
Gould E, Woolley CS, McEwen BS 1991 Adrenal steroids regulate postnatal development of the rat dentate gyrus: I. J Comp Neurol 313: 479–485
Oppenheimer JH, Schwartz HL 1997 Molecular basis of thyroid hormone-dependent brain development. Endocr Rev 18: 462–475
Bohn MC 1984 Glucocorticoid induced teratologies of the nervous system. In: Yanai J (ed) Neurobehavioral Teratology. Elsevier Science Publishers, New York, pp 365–387
Liggins GC, Howie RN 1972 A controlled trial of antepartum glucocorticoid treatment for the prevention of the respiratory distress syndrome in premature infants. Pediatrics 50: 515–523
NIH Consensus development conference. 1995 Effect of corticosteroids for fetal maturation and perinatal outcomes. Am J Obstet Gynecol 173: 253–344
Dodic M, Peers A, Coghlan JP, Wintour M 1999 Can excess glucocorticoid, in utero, predispose to cardiovascular and metabolic disease in middle age?. Trends Endocrinol Metab 10: 86–91
Takahashi LK 1998 Prenatal stress: consequences of glucocorticoids on hippocampal development and function. Int J Dev Neurosci 16: 199–207
Weinstock M 1997 Does prenatal stress impair coping and regulation of hypothalamic-pituitary-adrenal axis. Neurosci Biobehav Rev 21: 1–10
De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M 1998 Brain corticosteroid receptor balance in health and disease. Endocr Rev 19: 269–301
Beggs JM, Brown TH, Byrne JH, Crow T, LeDoux JE, LeBar K, Thompson RF 1999 Learning and memory: basic mechanisms. In: Zigmond MJ, Bloom FE, Landis SC, Roberts JL, Squire LR (eds) Fundamental Neuroscience. Academic Press, San Diego, pp 1411–1454
Jacobson L, Sapolsky R 1991 The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev 12: 118–134
Levine S 1957 Maternal and environmental influences on the adrenocortical response to stress in weanling rats. Science 156: 258–260
Herman JP, Prewitt CM, Cullinan WE 1996 Neuronal circuit regulation of the hypothalamo-pituitary-adrenocortical stress axis. Crit Rev Neurobiol 10: 371–394
Munck A, Guyre PM, Holbrook NJ 1984 Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5: 25–44
Lupien SJ, McEwen BS 1997 The acute effects of corticosteroids on cognition: integration of animal and human model studies. Brain Res Brain Res Rev 24: 1–27
Dobbing J, Sands J 1973 Quantitative growth and development of human brain. Arch Dis Child 48: 757–767
Dobbing J, Sands J 1979 Comparative aspects of the brain growth spurt. Early Hum Dev 3: 79–83
Matthews SG, Challis JRG 1996 Regulation of the hypothalamo-pituitary-adrenocortical axis in fetal sheep. Trends Endocrinol Metab 7: 239–246
Matthews SG 1998 Dynamic changes in glucocorticoid and mineralocorticoid receptor mRNA in the developing guinea pig brain. Dev Brain Res 107: 123–132
Sapolsky RM, Meaney MJ 1986 Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period. Brain Res Rev 396: 64–76
Claman HN 1972 Corticosteroids and lymphoid cells. N Engl J Med 287: 388–397
Dalle M, Delost P 1979 Foetal-maternal production and transfer of cortisol during the last days of gestation in the guinea-pig. J Endocrinol 82: 43–51
Edwards CRW, Benediktsson R, Lindsay RS, Seckl JR 1996 11β-Hydroxysteroid dehydrogenases: key enzymes in determining tissue-specific glucocorticoid effects. Steroids 61: 263–269
Seckl JR 1997 Glucocorticoids, feto-placental 11β-hydroxysteroid dehydrogenase type 2, and the early life origins of adult disease. Steroids 62: 89–94
Benediktsson R, Calder AA, Edwards CRW, Seckl JR 1997 Placental 11β-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure. Clin Endocrinol Oxf 46: 161–166
Sampath-Kumar R, Matthews SG, Yang K 1998 11β-hydroxysteroid dehydrogenase type 2 is the predominant isozyme in the guinea pig placenta: decreases in messenger ribonucleic acid and activity at term. Biol Reprod 59: 1378–1384
Stewart PM, Rogerson FM, Mason JI 1995 Type 2: 11β-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. J Clin Endocrinol Metab 80: 885–890
Antoni FA 1986 Hypothalamic control of adrenocorticotropin secretion: advances since the discovery of 41-residue corticotropin releasing hormone. Endocr Rev 7: 351–378
Whitnall MH 1993 Regulation of the hypothalamic corticotropin-releasing hormone neurosecretory system. Prog Neurobiol 40: 573–629
Plotsky PM 1991 Pathways to the secretion of adrenocorticotropin: a view from the portal. J Neuroendocrinol 3: 1–9
Miller WL, Tyrrell JB 1995 The adrenal cortex. In: Felig P, Baxter JD, Frohman LA (eds) Endocrinology and Metabolism. McGraw Hill, New York, pp 555–711
Seeman TE, Robbins RJ 1994 Aging and hypothalamic-pituitary-adrenal response to challenge in humans. Endocr Rev 15: 233–260
Plotsky PM, Thrivikraman KV, Meaney MJ 1993 Central and feedback regulation of hypothalamic corticotropin-releasing factor secretion. Ciba Found Symp 172: 59–75
Dallman MF, Akana SF, Levin N, Walker C-D, Bradbury MJ, Suemaru S, Scribner KS 1994 Corticosteroids and the control of function in the hypothalamo-pituitary-adrenal (HPA) axis. Ann NY Acad Sci 746: 22–32
Krozowski ZS, Funder JW 1983 Renal mineralocorticoid receptors and hippocampal corticosterone-binding species have identical intrinsic steroid specificity. Proc Natl Acad Sci USA 80: 6056–6060
Levitt NS, Lindsay RS, Holmes MC, Seckl JR 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: 412–418
Muneoka K, Mikuni M, Ogawa T, Kitera K, Kamei K, Takigawa M, Takahashi K 1997 Prenatal dexamethasone exposure alters brain monoamine metabolism and adrenocortical response in rat offspring. Am J Physiol 273: R1669–R1675
Bakker JM, Schmidt ED, Kroes H, Kavelaars A, Heijnen CJ, Tilders FJH, Van Rees EP 1995 Effects of short-term dexamethasone treatment during pregnancy on the development of the immune system and the hypothalamo-pituitary adrenal axis in the rat. J Neuroimmunol 63: 183–191
Dean F, Yu C, Matthews SG 1999 Maternal glucocorticoid treatment in late gestation programs hypothalamo-pituitary-adrenal function in guinea pig offspring. Endocrine Society, San Diego, Abstract P. 2: 397
Dean F, Matthews SG 1999 Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain. Brain Res 846: 253–259
Uno H, Eisele S, Sakai A, Shelton S, Baker E, DeJesus O, Holden J 1994 Neurotoxicity of glucocorticoids in the primate brain. Horm Behav 28: 336–348
Brindley DN, Rolland Y 1989 Possible connections between stress, diabetes, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis. Clin Sci 77: 453–461
Munck A, Náray-Fejes-Tóth A 1994 Glucocorticoids and stress: permissive and suppressive actions. Ann NY Acad Sci 746: 115–120
Ader R, Grota LJ 1973 Adrenocortical mediation of the effects of early life experiences. Prog Brain Res 39: 395–406
Diaz R, Fuxe K, Ögren SO 1997 Prenatal corticosterone treatment induces long-term changes in spontaneous and apomorphine-mediated motor activity in male and female rats. Neuroscience 81: 129–140
Holson RR, Gough B, Sullivan P, Badger T, Sheehan DM 1995 Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats. Neurotoxicol Teratol 17: 393–401
Gandelman R, Rosenthal C 1981 Deleterious effects of prenatal prednisolone exposure upon morphological and behavioral development of mice. Teratology 24: 293–301
Rayburn WF, Christensen HD, Gonzalez CL 1997 A placebo-controlled comparison between betamethasone and dexamethasone for fetal maturation: differences in neurobehavioral development of mice offspring. Am J Obstet Gynecol 176: 842–850
Rayburn WF, Christensen CL, Gonzalaz LA, Rayburn LA, Stewart JD 1998 Effect of in utero exposure to betamethasone on motivation/anxiety testing in mice offspring. Neurotoxicol Teratol 20: 475–481
Salokorpi T, Sajaniemi N, Hällback H, Kari A, Rita H, Von Wendt L 1997 Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta Paediatr 86: 294–298
MacArthur BA, Howie RN, Dezoete JA, Elkins J 1981 Cognitive and psychosocial development of 4-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 68: 638–643
MacArthur BA, Howie RN, Dezoete JA, Elkins J 1982 School progress and cognitive development of 6-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 70: 99–105
Smolders-de Hass H, Neuvel J, Schmand B, Treffers PE, Koppe JG, Hoeks J 1990 Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12-year follow-up. Pediatrics 86: 65–70
Dammann O, Walther H, Allers B, Schröder M, Drescher J, Lutz D, Veelken N, Schulte FJ 1996 Development of a regional cohort of very-low-birthweight children at six years: cognitive abilities are associated with neurological disability and social background. Dev Med Child Neurol 38: 97–108
Goldenberg RL, DuBard MB, Cliver SP, Nelson KG, Blankson K, Ramey SL, Herman A 1996 Pregnancy outcome and intelligence at age five years. Am J Obstet Gynecol 175: 1511–1515
McCarton CM, Wallace IF, Divon M, Vaughan HG Jr 1996 Cognitive and neurologic development of the premature, small for gestational age infant through age 6: comparison by birth weight and gestational age. Pediatrics 98: 1167–1178
Breslau N, Chilcoat H, DelDotto J, Andreski P, Brown G 1996 Low birth weight and neurocognitive status at six years of age. Biol Psychiatry 40: 389–397
Trautman PD, Meyer-Bahlburg HFL, Postelnek J, New MI 1995 Effects of early prenatal dexamethasone on the cognitive and behavioural development of young children: results of a pilot study. Psychoneuroendocrinology 20: 439–449
French NP, Hagan R, Evans SF, Godfrey M, Newnham JP 1999 Repeated antenatal corticosteroids: size at birth and subsequent development. Am J Obstet Gynecol 180: 114–121
Bohn MC, Dean D, Hussain S, Giuliano R 1994 Development of mRNAs for glucocorticoid and mineralocorticoid receptors in rat hippocampus. Dev Brain Res 77: 157–162
Rosenfeld P, van Eekelen JAM, Levine S, De Kloet ER 1993 Ontogeny of corticosteroid receptors in the brain. Cell Mol Neurobiol 13: 295–319
Meaney MJ, Sapolsky RM, McEwen BS 1985 The development of the glucocorticoid receptor system in the rat limbic brain: II. Dev Brain Res 18: 165–168
van Eekelen JAM, Bohn MC, De Kloet ER 1991 Postnatal ontogeny of mineralocorticoid and glucocorticoid receptor gene expression in regions of the rat tel- and diencephalon. Dev Brain Res 61: 33–43
Cintra A, Solfrini V, Bunnemann B, Okret S, Bortolotti F, Gustafsson J-Å, Fuxe K 1993 Prenatal development of glucocorticoid receptor gene expression and immunoreactivity in the rat brain and pituitary gland: a combined in situ hybridization and immunocytochemical analysis. Neuroendocrinology 57: 1133–1147
Kitraki E, Alexis MN, Papalopoulou M, Stylianopoulou F 1996 Glucocorticoid receptor gene expression in the embryonic rat brain. Neuroendocrinology 63: 305–317
Diaz R, Brown RW, Seckl JR 1998 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. J Neurosci 18: 2570–2580
Jones CT, Roebuck MM 1980 The development of the pituitary-adrenal axis in the guinea pig. Acta Endocrinol 94: 107–116
Andrews MH, Dean F, Matthews SG 1998 Hypothalamic glucocorticoid receptor and heat shock protein 70 expression during development in sheep: implications for negative feedback. Endocrine Society New Orleans 1: 401
Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterström RH, Perlmann T, Lehmann JM 1998 An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92: 73–82
Plotsky PM, Cunningham ETJ, Widmaier EP 1989 Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr Rev 10: 437–458
Cunningham ETJ, Sawchenko PE 1988 Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus. J Comp Neurol 274: 60–76
Cunningham ETJ, Bohn MC, Sawchenko PE 1990 Organization of adrenergic inputs to the paraventricular and supraoptic nuclei of the hypothalamus in the rat. J Comp Neurol 292: 651–667
Nakane H, Shimizu N, Hori T 1994 Stress-induced norepinephrine release in the rat prefrontal cortex measured by microdialysis. Am J Physiol 257: R1559–R1567
Nisenbaum LK, Abercrombie ED 1993 Presynaptic alterations associated with enhancement of evoked release and synthesis of norepinephrine in hippocampus of chronically cold-stressed rats. Brain Res 608: 280–287
Yau JLW, Seckl JR 1992 Central 6-hydroxydopamine lesions decrease mineralocorticoid, but not glucocorticoid receptor gene expression in the rat hippocampus. Neurosci Lett 142: 159–162
Slotkin TA, Lappi SE, McCook EC, Tayyeb MI, Eylers JP, Seidler FJ 1992 Glucocorticoids and the development of neuronal function: effects of prenatal dexamethasone exposure on central noradrenergic activity. Biol Neonate 61: 326–336
Slotkin TA, Lappi SE, Tayyeb MI, Seidler FJ 1991 Dose-dependent glucocorticoid effects on noradrenergic synaptogenesis in rat brain: ontogeny of [3H]desmethylimipramine binding sites after fetal exposure to dexamethasone. Res Commun Chem Pathol Pharmacol 73: 3–19
Barbazanges A, Piazza PV, Le Moal M, Maccari S 1996 Maternal glucocorticoid secretion mediates long-term effects of prenatal stress. J Neurosci 16: 3943–3949
Sawchenko PE, Swanson LW, Steinbush HW, Verhofstad AA 1983 The distribution and cells of origin of serotonergic inputs to the paraventricular and supraoptic nuclei of the rat. Brain Res 277: 355–360
Saphier D, Feldman S 1989 Paraventricular nucleus neuronal responses following electrical stimulation of the midbrain dorsal raphe: evidence for cotransmission. Exp Brain Res 78: 407–414
Gibbs DM, Vale WW 1983 Effect of the serotonin re-uptake inhibitor fluoxetine on corticotropin releasing factor and vasopressin secretion into the hypophyseal portal blood. Brain Res 280: 176–179
Calogero AE, Bagdy G, Moncada ML, D'Agata R 1993 Effect of selective serotonin agonists on basal, corticotrophin-releasing hormone- and vasopressin-induced ACTH release in vitro from rat pituitary cells. J Endocrinol 136: 381–387
Kageyama K, Tozawa F, Horiba N, Watanobe H, Suda T 1998 Serotonin stimulates corticotropin-releasing factor gene expression in the hypothalamic paraventricular nucleus of conscious rats. Neurosci Lett 243: 17–20
Hayashi A, Nagaoka M, Yamada K, Ichitani Y, Miake Y, Okado N 1998 Maternal stress induces synaptic loss and developmental disabilities of offspring. Int J Dev Neurosci 16: 209–216
Slotkin TA, Barnes GA, McCook EC, Seidler FJ 1996 Programming of brainstem serotonin transporter development by prenatal glucocorticoids. Dev Brain Res 93: 155–161
Semont A, Fache MP, Ouafik L, Hery M, Faudon M, Hery F 1999 Effect of serotonin inhibition on glucocorticoid and mineralocorticoid expression in various brain structures. Neuroendocrinology 69: 121–128
Bamberger CM, Schulte HM, Chrousos GP 1996 Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 17: 245–261
Ajilore OA, Sapolsky RM 1999 In vivo characterization of 11β-hydroxysteroid dehydrogenase in rat hippocampus using glucocorticoid neuroendangerment as an endpoint. Neuroendocrinology 69: 138–144
Seckl JR 1997 11β-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action?. Front Neuroendocrinol 18: 49–99
Bodine PV, Litwack G 1990 The glucocorticoid receptor and its endogenous regulators. Receptor 1: 83–119
Orti E, Bodwell JE, Munck A 1992 Phosphorylation of steroid hormone receptors. Endocr Rev 13: 105–128
Sanchez ER, Hu J-L, Zhong S, Shen P, Greene MJ, Housley PR 1994 Potentiation of glucocorticoid receptor-mediated gene expression by heat and chemical shock. Mol Endocrinol 8: 408–421
Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, Cato ACB 1994 A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J 13: 4087–4095
Webster JC, Cidlowski JA 1994 Downregulation of the glucocorticoid receptor: a mechanism for physiological adaptation to hormones. Ann NY Acad Sci 746: 216–220
Silva CM, Powell-Oliver F, Jewell CM, Sar M, Allgood VE, Cidlowski JA 1994 Regulation of the human glucocorticoid receptor by long-term and chronic treatment with glucocorticoid. Steroids 59: 436–442
Kalinyak JE, Griffin CA, Hamilton RW, Bradshaw JG, Perlman AJ, Hoffman AR 1989 Developmental and hormonal regulation of glucocorticoid receptor messenger RNA in the rat. J Clin Invest 84: 1843–1848
Meaney MJ, Sapolsky RM, McEwen BS 1985 The development of the glucocorticoid receptor system in the rat limbic brain: I. Dev Brain Res 18: 159–164
Mitchell JB, Rowe W, Boksa P, Meaney MJ 1990 Serotonin regulates type II corticosteroid receptor binding in hippocampal cell cultures. J Neurosci 10: 1745–1752
Anisman H, Zaharia MD, Meaney MJ, Merali Z 1998 Do early-life events permanently alter behavioral and hormonal responses to stressors?. Int J Dev Neurosci 16: 149–164
Meaney MJ, Diorio J, Francis D, Larocque S, O'Donnell D, Smythe JW, Sharma S, Tannenbáum B 1994 Environmental regulation of the development of glucocorticoid receptor systems in the rat forebrain: the role of serotonin. Ann NY Acad Sci 746: 260–274
Mitchell JB, Iny LJ, Meaney MJ 1990 The role of serotonin in the development and environmental regulation of type II corticosteroid receptor binding in rat hippocampus. Dev Brain Res 55: 231–235
Meaney MJ, Aitken DH, Sapolsky RM 1987 Thyroid hormones influence the development of hippocampal glucocorticoid receptors in the rat: a mechanism for the effects of postnatal handling on the development of the adrenocortical stress response. Neuroendocrinology 45: 278–283
Sapolsky RM 1999 Why stress is bad for your brain. Science 273: 749–750
Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW 1996 Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93: 3908–3913
Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB 1995 MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 152: 973–981
Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B 1997 Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med 27: 951–959
Uno H, Lohmiller L, Thieme C, Kemnitz JW, Engle MJ, Roecker EB, Farrell PM 1990 Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques: I. Dev Brain Res 53: 157–167
De Kloet ER, Rosenfeld P, Van Eikelen JA, Sutanto W, Levine S 1988 Stress, glucocorticoids and development. Prog Brain Res 73: 101–120
Sapolsky RM 1996 Stress, glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1: 1–19
Horner HC, Packan DR, Sapolsky RM 1990 Glucocorticoids inhibit glucose transport in cultured hippocampal neurons and glia. Neuroendocrinology 52: 57–64
Lawrence MS, Sapolsky RM 1994 Glucocorticoids accelerate ATP loss following metabolic insults in cultured hippocampal neurons. Brain Res 646: 303–306
Dunlop SA, Archer MA, Quinlivan JA, Beazley LD, Newnham JP 1997 Repeated prenatal corticosteroids delay myelination in the ovine central nervous system. J Matern Fetal Med 6: 309–313
Carlos RQ, Seidler FJ, Slotkin TA 1992 Fetal dexamethasone exposure alters macromolecular characteristics of rat brain development: a critical period for regionally selective alterations?. Teratology 46: 45–59
Carlos RQ, Seidler FJ, Lappi SE, Slotkin TA 1991 Fetal dexamethasone exposure affects basal ornithine decarboxylase activity in developing rat brain regions and alters acute responses to hypoxia and maternal separation. Biol Neonate 59: 69–77
Rodriguez JJ, Montaron MF, Petry KG, Aurousseau C, Marinelli M, Premier S, Rougon G, Le Moal M, Abrous DN 1998 Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus. Eur J Neurosci 10: 2994–3006
Rose SP 1995 Cell adhesion molecules, glucocorticoids and long-term memory formation. Trends Neurosci 18: 502–506
Slotkin TA, Zhang J, McCook EC, Seidler FJ 1998 Glucocorticoid administration alters nuclear transcription factors in fetal rat brain: implications for the use of antenatal steroids. Brain Res Dev Brain Res 111: 11–24
Slotkin TA, Lau C, Lappi FJ, Seidler FJ 1996 Can intracellular signaling pathways predict developmental abnormalities? Sensitivity of the adenyl cyclase/c-fos proto-oncogene cascade to β-adrenergic agonists and glucocorticoids in the fetal rat. Biomarkers 1: 115–122
Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS 1994 Neurotropic factors: from molecule to man. Trends Neurosci 17: 182–190
Collazo D, Takahashi H, McKay RD 1992 Cellular targets and trophic functions of neurotrophin-3 in the developing rat hippocampus. Neuron 9: 643–656
Smith MA, Makino S, Kvetnansky R, Post RM 1995 Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15: 1768–1777
Smith MA, Makino S, Kim SY, Kvetnansky R 1995 Stress increases brain-derived neurotropic factor messenger ribonucleic acid in the hypothalamus and pituitary. Endocrinology 136: 3743–3750
Smith MA 1996 Hippocampal vulnerability to stress and aging: possible role of neurotrophic factors. Behav Brain Res 78: 25–36
Chao HM, McEwen BS 1994 Glucocorticoids and the expression of mRNAs for neurotrophins, their receptors and GAP-43 in the rat hippocampus. Brain Res Mol Brain Res 26: 271–276
Maisonpierre PC, Belluscio L, Friedman B, Alderson RF, Wiegand SJ, Furth ME, Lindsay RM, Yancopoulos GD 1990 NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 5: 501–509
Seckl JR, Olsson T 1995 Glucocorticoid hypersecretion and the age-impaired hippocampus: cause or effect. J Endocrinol 145: 201–211
Marinoni E, Korebrits C, Di Iorio R, Cosmi EV, Challis JR 1998 Effect of betamethasone in vivo on placental corticotropin-releasing hormone in human pregnancy. Am J Obstet Gynecol 178: 770–778
Marinoni E, Di Iorio R, Letizia C, Villaccio B, Scucchi L, Cosmi EV 1998 Immunoreactive adrenomedullin in human fetoplacental tissues. Am J Obstet Gynecol 179: 784–787
Clifton VL, Owens PC, Robinson PJ, Smith R 1995 Identification and characterization of a corticotrophin-releasing hormone receptor in human placenta. Eur J Endocrinol 133: 591–597
Clifton VL, Read MA, Leitch IM, Boura ALA, Robinson PJ, Smith R 1994 Corticotropin-releasing hormone-induced vasodilatation in the human fetal placental circulation. J Clin Endocrinol Metab 79: 666–669
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Matthews, S. Antenatal Glucocorticoids and Programming of the Developing CNS. Pediatr Res 47, 291–300 (2000). https://doi.org/10.1203/00006450-200003000-00003
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DOI: https://doi.org/10.1203/00006450-200003000-00003
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