Journal of Physiology and Biochemistry

, Volume 69, Issue 3, pp 559–573 | Cite as

The physiological roles of placental corticotropin releasing hormone in pregnancy and childbirth

Mini Review


In response to stress, the hypothalamus releases cortiticotropin releasing hormone (CRH) that travels to the anterior pituitary, where it stimulates the release of adrenocorticotropic hormone (ACTH). ACTH travels to the adrenal cortex, where it stimulates the release of cortisol and other steroids that liberate energy stores to cope with the stress. During pregnancy, the placenta synthesises CRH and releases it into the bloodstream at increasing levels to reach concentrations 1,000 to 10, 000 times of that found in the non-pregnant individual. Urocortins, which are CRH analogues are also secreted by the placenta. Desensitisation of the maternal pituitary to CRH and resetting after birth may be a factor in post-partum depression. Recently, CRH has been found to modulate glucose transporter (GLUT) proteins in placental tissue, and therefore there may be a link between CRH levels and foetal growth. Evidence suggests CRH is involved in the timing of birth by modulating signalling systems that control the contractile properties of the myometrium. In the placenta, cortisol stimulates CRH synthesis via activation of nuclear factor kappa B (NF-κB), a component in a cellular messenger system that may also be triggered by stressors such as hypoxia and infection, indicating that intrauterine stress could bring forward childbirth and cause low birth weight infants. Such infants could suffer health issues into their adult life as a result of foetal programming. Future treatment of these problems with CRH antagonists is an exciting possibility.


Corticotropin releasing hormone (CRH) Adrenocorticotropic hormone (ACTH) Cortisol Placenta Pituitary Growth restriction Foetus Foetal programming Diabetes Obesity Hypertension Atherosclerosis 


  1. 1.
    Abou-Seif C, Shipman KL, Allars M, Norris MH, Chen YX, Smith R, Nicholson RC (2012) Tissue specific epigenetic differences in CRH gene expression. Front Biosci 17:713–725CrossRefGoogle Scholar
  2. 2.
    Aguilar HN, Mitchell BF (2010) Physiological pathways and molecular mechanisms regulating uterine contractility. Hum Reprod Update 16:725–744PubMedCrossRefGoogle Scholar
  3. 3.
    Aye ILMH, Waddell BJ, Mark PJ, Keelan JA (2012) Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF-κB. Mol Hum Reprod 18:341–353PubMedCrossRefGoogle Scholar
  4. 4.
    Baes CVW, Tofoli SMC, Martins CMS, Juruena MF (2012) Assessment of the hypothalamic–pituitary–adrenal axis activity: glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress — a systematic review. Acta Neuropsychiatr 24:4–15CrossRefGoogle Scholar
  5. 5.
    Bale TL, Chen A (2012) Minireview: CRF and Wylie Vale: a story of 41 amino acids and a Texan with grit. Endocrinology 153:2556–2561PubMedCrossRefGoogle Scholar
  6. 6.
    Bale TL, Vale WW (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol 44:525–557CrossRefGoogle Scholar
  7. 7.
    Barker DJP (2006) Adult consequences of fetal growth restriction. Clin Obstet Gynecol 49:270–283PubMedCrossRefGoogle Scholar
  8. 8.
    Bauer ME (2005) Stress, glucocorticoids and ageing of the immune system. Stress 8:69–83PubMedCrossRefGoogle Scholar
  9. 9.
    Beck CT (2008) State of the science on postpartum depression: what nurse researchers have contributed — part 1. MCN Am J Matern Child Nurs 33:121–126PubMedCrossRefGoogle Scholar
  10. 10.
    Bloom SL, Sheffield JS, McIntire DD, Leveno KJ (2001) Antenatal dexamethasone and decreased birth weight. Obstet Gynecol 97:485–490PubMedCrossRefGoogle Scholar
  11. 11.
    Bortolotti B, Menchetti M, Bellini F, Montaguti MB, Berardi D (2008) Psychological interventions for major depression in primary care: a meta-analytic review of randomized controlled trials. Gen Hosp Psychiat 30:293–302CrossRefGoogle Scholar
  12. 12.
    Breuiller-Fouche M, Germain G (2006) Gene and protein expression in the myometrium in pregnancy and labor. Reproduction 131:837–850PubMedCrossRefGoogle Scholar
  13. 13.
    Campbell EA, Linton EA, Wolfe CDA, Scraggs PR, Jones MT, Lowry PJ (1987) Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. J Clin Endocr Metab 64:1054–1059PubMedCrossRefGoogle Scholar
  14. 14.
    Challis JRG, Matthews SG, Gibb W, Lye SJ (2000) Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev 21:514–550PubMedCrossRefGoogle Scholar
  15. 15.
    Chang CL, Hsu SY (2004) Ancient evolution of stress-regulating peptides in vertebrates. Peptides 25:1681–1688PubMedCrossRefGoogle Scholar
  16. 16.
    Chen R, Lewis KA, Perrin MH, Vale WW (1993) Expression cloning of a human corticotropin-releasing-factor receptor. Proc Natl Acad Sci USA 90:8967–8971PubMedCrossRefGoogle Scholar
  17. 17.
    Chen L, Sooranna SR, Lei K, Kandola M, Bennett PR, Liang Z, Grammatopoulos D, Johnson MR (2012) Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells. J Cell Mol Med 16:1447–1460PubMedCrossRefGoogle Scholar
  18. 18.
    Claes SJ (2004) Corticotropin-releasing hormone (CRH) in psychiatry: from stress to psychopathology. Ann Med 36:50–61PubMedCrossRefGoogle Scholar
  19. 19.
    Cong B, Zhang L, Gao L, Ni X (2009) Reduced expression of CRH receptor type 1 in upper segment human myometrium during labour. Reprod Biol Endocrinol 7:43PubMedCrossRefGoogle Scholar
  20. 20.
    Coufalik AH, Monder C (1981) Stimulation of gluconeogenesis by cortisol in fetal rat liver in organ culture. Endocrinology 108:1132–1137PubMedCrossRefGoogle Scholar
  21. 21.
    DeBold CR, DeCherney GS, Jackson RV, Sheldon WR, Alexander AN, Island DP, Rivier J, Vale W, Orth DN (1983) Effect of synthetic ovine corticotropin-releasing factor: prolonged duration of action and biphasic response of plasma adrenocorticotropin and cortisol. J Clin Endocr Metab 57:294–298PubMedCrossRefGoogle Scholar
  22. 22.
    Dores RM, Baron AJ (2011) Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins. Ann NY Acad Sci 1220:34–48PubMedCrossRefGoogle Scholar
  23. 23.
    Drake AJ, Seckl JR (2011) Transmission of programming effects across generations. Pediatr Endocrinol Rev 9:566–578PubMedGoogle Scholar
  24. 24.
    Fetalvero KM, Zhang P, Shyu M, Young BT, Hwa J, Young RC, Martin KA (2008) Prostacyclin primes pregnant human myometrium for an enhanced contractile response in parturition. J Clin Invest 118:3966–3979PubMedGoogle Scholar
  25. 25.
    Florio P, Lowry PJ, Benedetto C, Galleri L, Torricelli M, Giovannelli A, Battista R, Reis FM, Petraglia F (2007) Maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) levels in post-term pregnancy: effect of prostaglandin administration. Eur J Endocrinol 157:279–284PubMedCrossRefGoogle Scholar
  26. 26.
    Gao L, Lu C, Xu C, Tao Y, Cong B, Ni X (2008) Differential regulation of prostaglandin production mediated by corticotropin-releasing hormone receptor type 1 and type 2 in cultured human placental trophoblasts. Endocrinology 149:2866–2876PubMedCrossRefGoogle Scholar
  27. 27.
    Gao L, Lv C, Xu C, Li Y, Cui X, Gu H, Ni X (2012) Differential regulation of glucose transporters mediated by CRH receptor type 1 and type 2 in human placental trophoblasts. Endocrinology 153:1464–1471PubMedCrossRefGoogle Scholar
  28. 28.
    Gilpin NW (2012) Corticotropin-releasing factor (CRF) and neuropeptide Y (NPY): effects on inhibitory transmission in central amygdala, and anxiety- and alcohol-related behaviors. Alcohol 46:329–337PubMedCrossRefGoogle Scholar
  29. 29.
    Gold PW, Loriaux DL, Roy A, Kling MA, Calabrese JR, Kellner CH, Nieman LK, Post RM, Pickar D, Gallucci W, Avgerinos P, Paul S, Oldfield EH, Cutler GB, Chrousos GP (1986) Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. New Engl J Med 314:1329–1335PubMedCrossRefGoogle Scholar
  30. 30.
    Grammatopoulos DK (2007) The role of CRH receptors and their agonists in myometrial contractility and quiescence during pregnancy and labour. Front Biosci 12:561–571PubMedCrossRefGoogle Scholar
  31. 31.
    Grammatopoulos D, Dai Y, Chen J, Karteris E, Papadopoulou N, Easton AJ, Hillhouse EW (1998) Human corticotropin-releasing hormone receptor: differences in subtype expression between pregnant and nonpregnant myometria. J Clin Endocr Metab 83:2539–2544PubMedCrossRefGoogle Scholar
  32. 32.
    Grammatopoulos D, Stirrat GM, Williams SA, Hillhouse EW (1996) The biological activity of the corticotropin-releasing hormone receptor–adenylate cyclase complex in human myometrium is reduced at the end of pregnancy. J Clin Endocr Metab 81:745–751PubMedCrossRefGoogle Scholar
  33. 33.
    Hahn T, Barth S, Graf R, Engelmann M, Beslagic D, Reul JMHM, Holsboer F, Dohr G, Desoye G (1999) Placental glucose transporter expression is regulated by glucocorticoids. J Clin Endocr Metab 84:1445–1452PubMedCrossRefGoogle Scholar
  34. 34.
    Handley SL, Dunn TL, Waldron G, Baker JM (1980) Tryptophan, cortisol and puerperal mood. Brit J Psychiat 136:498–508PubMedCrossRefGoogle Scholar
  35. 35.
    Hayashi M, Sakata M, Takeda T, Yamamoto T, Okamoto Y, Sawada K, Kimura A, Minekawa R, Tahara M, Tasaka K, Murata Y (2004) Induction of glucose transporter 1 expression through hypoxia-inducible factor 1a under hypoxic conditions in trophoblast-derived cells. J Endocrinol 183:145–154PubMedCrossRefGoogle Scholar
  36. 36.
    Hertelendy F, Zakar T (2004) Regulation of myometrial smooth muscle functions. Curr Pharm Design 10:2499–2517CrossRefGoogle Scholar
  37. 37.
    Hillhouse EW, Grammatopoulos DK (2002) Role of stress peptides during human pregnancy and labour. Reproduction 124:323–329PubMedCrossRefGoogle Scholar
  38. 38.
    Hillhouse EW, Grammatopoulos DK (2006) The molecular mechanisms underlying the regulation of the biological activity of corticotropin-releasing hormone receptors: implications for physiology and pathophysiology. Endocr Rev 27:260–286PubMedCrossRefGoogle Scholar
  39. 39.
    Himes KP, Simhan HN (2011) Plasma corticotropin-releasing hormone and cortisol concentrations and perceived stress among pregnant women with preterm and term birth. Am J Perinatol 28:443–448PubMedCrossRefGoogle Scholar
  40. 40.
    Holsboer F, Vonbardeleben U, Gerken A, Stalla GK, Muller OA (1984) Blunted corticotropin and normal cortisol response to human corticotropin-releasing factor in depression. New Engl J Med 311:1127PubMedGoogle Scholar
  41. 41.
    Imperatore A, Rolfo A, Petraglia F, Challis JRG, Caniggia I (2010) Hypoxia and preeclampsia: increased expression of Urocortin 2 and Urocortin 3. Reprod Sci 17:833–843PubMedCrossRefGoogle Scholar
  42. 42.
    Ishimoto H, Jaffe RB (2011) Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit. Endocr Rev 32:317–355PubMedCrossRefGoogle Scholar
  43. 43.
    Jin D, He P, You X, Zhu X, Dai L, He Q, Liu C, Hui N, Sha J, Ni X (2007) Expression of corticotropin-releasing hormone receptor type 1 and type 2 in human pregnant myometrium. Reprod Sci 14:568–577PubMedCrossRefGoogle Scholar
  44. 44.
    Karteris E, Hillhouse EW, Grammatopoulos D (2004) Urocortin II is expressed in human pregnant myometrial cells and regulates myosin light chain phosphorylation: potential role of the type-2 corticotropin-releasing hormone receptor in the control of myometrial contractility. Endocrinology 145:890–900PubMedCrossRefGoogle Scholar
  45. 45.
    Karteris E, Markovic D, Chen J, Hillhouse EW, Grammatopoulos DK (2010) Identification of a novel corticotropin-releasing hormone type 1β-like receptor variant lacking exon 13 in human pregnant myometrium regulated by estradiol-17β and progesterone. Endocrinology 151:4959–4968PubMedCrossRefGoogle Scholar
  46. 46.
    Khan H, Kusakabe KT, Wakitani S, Hiyama M, Kiso Y (2011) Quantitative expression and immunohistochemical detection of glucose transporters, GLUT1 and GLUT3 in the rabbit placenta during successful pregnancy. J Vet Med Sci 73:1177–1183PubMedCrossRefGoogle Scholar
  47. 47.
    Khan RN, Matharoo-Ball B, Arulkumaran S, Ashford MLJ (2001) Potassium channels in the human myometrium. Exp Physiol 86:255–264PubMedCrossRefGoogle Scholar
  48. 48.
    Kipmen-Korgun D, Ozmen A, Unek G, Simsek M, Demir R, Korgun ET (2012) Triamcinolone up-regulates GLUT 1 and GLUT 3 expression in cultured human placental endothelial cells. Cell Biochem Funct 30:47–53CrossRefGoogle Scholar
  49. 49.
    Korebrits C, Ramirez MM, Watson L, Brinkman E, Bocking AD, Challis JRG (1998) Maternal corticotropin-releasing hormone is increased with impending preterm birth. J Clin Endocr Metab 83:1585–1591PubMedCrossRefGoogle Scholar
  50. 50.
    Kovo M, Schreiber L, Ben-Haroush A, Asalee L, Seadia S, Golan A, Bar J (2011) The placental factor in spontaneous preterm labor with and without premature rupture of membranes. J Perinat Med 39:423–429PubMedCrossRefGoogle Scholar
  51. 51.
    Kramer MS, Lydon J, Seguin L, Goulet L, Kahn SR, McNamara H, Genest J, Dassa C, Chen MF, Sharma S, Meaney MJ, Thomson S, Van Uum S, Koren G, Dahhou M, Lamoureux J, Platt RW (2009) Stress pathways to spontaneous preterm birth: the role of stressors, psychological distress, and stress hormones. Am J Epidemiol 169:1319–1326PubMedCrossRefGoogle Scholar
  52. 52.
    Langdown ML, Sugden MC (2001) Enhanced placental GLUT1 and GLUT3 expression in dexamethasone-induced fetal growth retardation. Mol Cell Endocrinol 185:109–117PubMedCrossRefGoogle Scholar
  53. 53.
    Lee M-J, Wang Z, Yee H, Ma Y, Swenson N, Yang L, Kadner SS, Baergen RN, Logan SK, Garabedian MJ, Guller S (2005) Expression and regulation of glucocorticoid receptor in human placental villous fibroblasts. Endocrinology 146:4619–4626PubMedCrossRefGoogle Scholar
  54. 54.
    Ling J, Kumar R (2012) Crosstalk between NFkB and glucocorticoid signaling: a potential target of breast cancer therapy. Cancer Lett 322:119–126PubMedCrossRefGoogle Scholar
  55. 55.
    Linton EA, Perkins AV, Woods RJ, Eben F, Wolfe CDA, Behan DP, Potter E, Vale WW, Lowry PJ (1993) Corticotropin releasing hormone-binding protein (CRH-BP): plasma levels decrease during the 3rd trimester of normal human pregnancy. J Clin Endocr Metab 76:260–262PubMedCrossRefGoogle Scholar
  56. 56.
    Linton EA, Wolfe CDA, Behan DP, Lowry PJ (1988) A specific carrier substance for human corticotrophin releasing factor in late gestational maternal plasma which could mask the ACTH-releasing activity. Clin Endocrinol 28:315–324CrossRefGoogle Scholar
  57. 57.
    Lockwood CJ (1999) Stress-associated preterm delivery: the role of corticotropin-releasing hormone. Am J Obstet Gynecol 180:S264–S266PubMedCrossRefGoogle Scholar
  58. 58.
    Magiakou MA, Mastorakos G, Rabin D, Dubbert B, Gold PW, Chrousos GP (1996) Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time. J Clin Endocr Metab 81:1912–1917PubMedCrossRefGoogle Scholar
  59. 59.
    Mancuso RA, Schetter CD, Rini CM, Roesch SC, Hobel CJ (2004) Maternal prenatal anxiety and corticotropin-releasing hormone associated with timing of delivery. Psychosom Med 66:762–769PubMedCrossRefGoogle Scholar
  60. 60.
    Mandl M, Ghaffari-Tabrizi N, Haas J, Nöhammer G, Desoye G (2006) Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines. Reproduction 132:159–167PubMedCrossRefGoogle Scholar
  61. 61.
    Melvin A, Mudie S, Rocha S (2011) Mechanism of hypoxia-induced NFkB. Cell Cycle 10:879–882PubMedCrossRefGoogle Scholar
  62. 62.
    Myers B, McKlveen JM, Herman JP (2012) Neural regulation of the stress response: the many faces of feedback. Cell Mol Neurobiol 32:683–694CrossRefGoogle Scholar
  63. 63.
    Nitta A, Ohmiya M, Sometani A, Itoh M, Nomoto H, Furukawa Y, Furukawa S (1999) Brain-derived neurotrophic factor prevents neuronal cell death induced by corticosterone. J Neurosci Res 57:227–235PubMedCrossRefGoogle Scholar
  64. 64.
    Nugent BM, Tobet SA, Lara HE, Lucion AB, Wilson ME, Recabarren SE, Paredes AH (2012) Hormonal programming across the lifespan. Horm Metab Res 44:577–586PubMedCrossRefGoogle Scholar
  65. 65.
    O’Keane V, Lightman S, Patrick K, Marsh M, Papadopoulos AS, Pawlby S, Seneviratne G, Taylor A, Moore R (2011) Changes in the maternal hypothalamic–pituitary–adrenal axis during the early puerperium may be related to the postpartum ‘blues’. J Neuroendocrinol 23:1149–1155PubMedCrossRefGoogle Scholar
  66. 66.
    O'Keane V, Lightman S, Marsh M, Pawlby S, Papadopoulos AS, Taylor A, Moore R, Patrick K (2011) Increased pituitary–adrenal activation and shortened gestation in a sample of depressed pregnant women: a pilot study. J Affect Disorders 130:300–305PubMedCrossRefGoogle Scholar
  67. 67.
    Orth DN, Mount CD (1987) Specific high-affinity binding protein for human corticotropin-releasing hormone in normal human plasma. Biochem Biophys Res Commun 143:411–417PubMedCrossRefGoogle Scholar
  68. 68.
    Paiva P, Whitehead C, Saglam B, Palmer K, Tong S (2011) Measurement of mRNA transcripts of very high placental expression in maternal blood as biomarkers of preeclampsia. J Clin Endocr Metab 96:E1807–E1815PubMedCrossRefGoogle Scholar
  69. 69.
    Palazidou E (2012) The neurobiology of depression. Brit Med Bull 101:127–145PubMedCrossRefGoogle Scholar
  70. 70.
    Pato MD, Adelstein RS (1980) Dephosphorylation of the 20,000-dalton light chain of myosin by two different phosphatases from smooth muscle. J Biol Chem 255:6535–6538PubMedGoogle Scholar
  71. 71.
    Pearlstein T (2008) Perinatal depression: treatment options and dilemmas. J Psychiat Neurosci 33:302–318Google Scholar
  72. 72.
    Peckett AJ, Wright DC, Riddell MC (2011) The effects of glucocorticoids on adipose tissue lipid metabolism. Metabolism 60:1500–1510PubMedCrossRefGoogle Scholar
  73. 73.
    Perrin M, Donaldson C, Chen R, Blount A, Berggren T, Bilezikjian L, Sawchenko P, Vale W (1995) Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart. P Natl Acad Sci USA 92:2969–2973CrossRefGoogle Scholar
  74. 74.
    Petraglia F, Sawchenko PE, Rivier J, Vale W (1987) Evidence for local stimulation of ACTH secretion by corticotropin-releasing factor in human placenta. Nature 328:717–719PubMedCrossRefGoogle Scholar
  75. 75.
    Power ML, Williams LE, Gibson SV, Schulkin J, Helfers J, Zorrilla EP (2010) Pattern of maternal circulating CRH in laboratory-housed squirrel and owl monkeys. Am J Primatol 72:1004–1012PubMedCrossRefGoogle Scholar
  76. 76.
    Rivier C, Brownstein M, Spiess J, Rivier J, Vale W (1982) In vivo corticotropin-releasing factor-induced secretion of adrenocorticotropin, β-endorphin, and corticosterone. Endocrinology 110:272–278PubMedCrossRefGoogle Scholar
  77. 77.
    Robinson BG, Arbiser JL, Emanuel RL, Majzoub JA (1989) Species-specific placental corticotropin releasing hormone messenger RNA and peptide expression. Mol Cell Endocrinol 62:337–341PubMedCrossRefGoogle Scholar
  78. 78.
    Robinson BG, Emanuel RL, Frim DM, Majzoub JA (1988) Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta. P Natl Acad Sci USA 85:5244–5248CrossRefGoogle Scholar
  79. 79.
    Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, Chaiworapongsa T, Mazor M (2006) The preterm parturition syndrome. BJOG-Int J Obstet Gy 113:17–42CrossRefGoogle Scholar
  80. 80.
    Romero R, Gómez R, Chaiworapongsa T, Conoscenti G, Cheol Kim J, Mee Kim Y (2001) The role of infection in preterm labour and delivery. Paediatr Perinat Epidemiol 15:41–56PubMedCrossRefGoogle Scholar
  81. 81.
    Ryabinin AE, Tsoory MM, Kozicz T, Thiele TE, Neufeld-Cohen A, Chen A, Lowery-Gionta EG, Giardino WJ, Kaur S (2012) Urocortins: CRF's siblings and their potential role in anxiety, depression and alcohol drinking behavior. Alcohol 46:349–357PubMedCrossRefGoogle Scholar
  82. 82.
    Saijonmaa O, Laatikainen T, Wahlström T (1988) Corticotrophin-releasing factor in human placenta: localization, concentration and release in vitro. Placenta 9:373–385PubMedCrossRefGoogle Scholar
  83. 83.
    Sandman CA, Davis EP, Buss C, Glynn LM (2011) Prenatal programming of human neurological function. Int J Pept 2011:837596Google Scholar
  84. 84.
    Shibasaki T, Odagiri E, Shizume K, Ling N (1982) Corticotropin-releasing factor-like activity in human placental extracts. J Clin Endocr Metab 55:384–386PubMedCrossRefGoogle Scholar
  85. 85.
    Sibai B, Meis PJ, Klebanoff M, Dombrowski MP, Weiner SJ, Moawad AH, Northen A, Iams JD, Varner MW, Caritis SN, O'Sullivan MJ, Miodovnik M, Leveno KJ, Conway D, Wapner RJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S (2005) Plasma CRH measurement at 16 to 20 weeks' gestation does not predict preterm delivery in women at high-risk for preterm delivery. Am J Obstet Gynecol 193:1181–1186PubMedCrossRefGoogle Scholar
  86. 86.
    Smith R, Cubis J, Brinsmead M, Lewin T, Singh B, Owens P, Chan EC, Hall C, Adler R, Lovelock M, Hurt D, Rowley M, Nolan M (1990) Mood changes, obstetric experience and alterations in plasma cortisol, beta-endorphin and corticotropin releasing hormone during pregnancy and the puerperium. J Psychosom Res 34:53–69PubMedCrossRefGoogle Scholar
  87. 87.
    Smith R, Maiti K (2012) The placenta, a transducer linking maternal nutrition to adult disease in the offspring? Endocrinology 153:1572–1574PubMedCrossRefGoogle Scholar
  88. 88.
    Smith R, Nicholson RC (2007) Corticotrophin releasing hormone and the timing of birth. Front Biosci 12:912–918PubMedCrossRefGoogle Scholar
  89. 89.
    Smith R, Thomson M (1991) Neuroendocrinology of the hypothalamo–pituitary–adrenal axis in pregnancy and the puerperium. Baillière Clinical Endoc 5:167–186CrossRefGoogle Scholar
  90. 90.
    Stalla GK, Hartwimmer J, von Werder K, Muller OA (1984) Ovine (o) and human (h) corticotrophin releasing factor (CRF) in man: CRF-stimulation and CRF-immunoreactivity. Acta Endocrinol (Copenh) 106:289–297Google Scholar
  91. 91.
    Stevens MY, Challis JRG, Lye SJ (1998) Corticotropin-releasing hormone receptor subtype 1 is significantly up-regulated at the time of labor in the human myometrium. J Clin Endocr Metab 83:4107–4115PubMedCrossRefGoogle Scholar
  92. 92.
    Struwe E, Berzl G, Schild R, Blessing H, Drexel L, Hauck B, Tzschoppe A, Weidinger M, Sachs M, Scheler C, Schleussner E, Dötsch J (2010) Microarray analysis of placental tissue in intrauterine growth restriction. Clin Endocrinol 72:241–247CrossRefGoogle Scholar
  93. 93.
    Takeda K, Akira S (2004) TLR signaling pathways. Semin Immunol 16:3–9PubMedCrossRefGoogle Scholar
  94. 94.
    Thomson M (1998) Does the CRH binding protein shield the anterior pituitary from placental CRH? Endocrine 9:221–226PubMedCrossRefGoogle Scholar
  95. 95.
    Thomson M (2008) The effects of placental corticotrophin releasing hormone on the physiology and psychology of the pregnant woman. Curr Women Health Rev 4:270–279CrossRefGoogle Scholar
  96. 96.
    Thomson M, Chan EC, Falconer J, Madsen G, Geraghty S, Curryer N, Boulton J, Smith R (1990) Desensitization of superfused isolated ovine anterior pituitary cells to human corticotropin-releasing factor. J Neuroendocrinol 2:181–187PubMedCrossRefGoogle Scholar
  97. 97.
    Thomson M, Chan EC, Falconer J, Madsen G, Smith R (1988) Secretion of corticotropin-releasing hormone by superfused human placental fragments. Gynecol Endocrinol 2:87–100PubMedCrossRefGoogle Scholar
  98. 98.
    Thomson F, Craighead M (2008) Innovative approaches for the treatment of depression: targeting the HPA axis. Neurochem Res 33:691–707PubMedCrossRefGoogle Scholar
  99. 99.
    Thomson M, Smith R (1989) The action of hypothalamic and placental corticotropin releasing factor on the corticotrope. Mol Cell Endocrinol 62:1–12PubMedCrossRefGoogle Scholar
  100. 100.
    Tizabi Y, Aguilera G (1992) Desensitization of the hypothalamic–pituitary–adrenal axis following prolonged administration of corticotropin-releasing hormone or vasopressin. Neuroendocrinology 56:611–618PubMedCrossRefGoogle Scholar
  101. 101.
    Torricelli M, Ignacchiti E, Giovannelli A, Merola A, Scarpetti E, Calonaci G, Picciolini E, Florio P, Reis FM, Linton EA, Petraglia F (2006) Maternal plasma corticotrophin-releasing factor and urocortin levels in post-term pregnancies. Eur J Endocrinol 154:281–285PubMedCrossRefGoogle Scholar
  102. 102.
    Torricelli M, Novembri R, Bloise E, De Bonis M, Challis JR, Petraglia F (2011) Changes in placental CRH, urocortins, and CRH-receptor mRNA expression associated with preterm delivery and chorioamnionitis. J Clin Endocr Metab 96:534–540PubMedCrossRefGoogle Scholar
  103. 103.
    Torricelli M, Voltolini C, Bloise E, Biliotti G, Giovannelli A, De Bonis M, Imperatore A, Petraglia F (2009) Urocortin increases IL-4 and IL-10 secretion and reverses LPS-induced TNF-α release from human trophoblast primary cells. Am J Reprod Immunol 62:224–231PubMedCrossRefGoogle Scholar
  104. 104.
    Tyson EK, Smith R, Read M (2009) Evidence that corticotropin-releasing hormone modulates myometrial contractility during human pregnancy. Endocrinology 150:5617–5625PubMedCrossRefGoogle Scholar
  105. 105.
    Tzschoppe AA, Struwe E, Dörr HG, Goecke TW, Beckmann MW, Schild RL, Dötsch J (2010) Differences in gene expression dependent on sampling site in placental tissue of fetuses with intrauterine growth restriction. Placenta 31:178–185PubMedCrossRefGoogle Scholar
  106. 106.
    Uh A, Nicholson RC, Gonzalez GV, Simmons CF, Gombart A, Smith R, Equils O (2008) Lipopolysaccharide stimulation of trophoblasts induces corticotropin-releasing hormone expression through MyD88. Am J Obstet Gynecol 199:317.e1–317.e6CrossRefGoogle Scholar
  107. 107.
    Uh A, Simmons CF, Bresee C, Khoury N, Gombart AF, Nicholson RC, Kocak H, Equils O (2009) MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line. Reprod Biol Endocrinol 7:74PubMedCrossRefGoogle Scholar
  108. 108.
    Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397PubMedCrossRefGoogle Scholar
  109. 109.
    Vallabhapurap S, Karin M (2009) Regulation and function of NF-κB transcription factors in the immune system. Ann Rev Immunol 27:693–733CrossRefGoogle Scholar
  110. 110.
    Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C, Rivier J, Sawchenko PE, Vale W (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378:287–292PubMedCrossRefGoogle Scholar
  111. 111.
    Wang B, Parobchak N, Rosen T (2012) RelB/NF-κB2 regulates corticotropin-releasing hormone in the human placenta. Mol Endocrinol 26:1356–1369PubMedCrossRefGoogle Scholar
  112. 112.
    Weiser MJ, Osterlund C, Spencer RL (2011) Inhibitory effects of corticosterone in the hypothalamic paraventricular nucleus (PVN) on stress-induced adrenocorticotrophic hormone secretion and gene expression in the PVN and anterior pituitary. J Neuroendocrinol 23:1231–1240PubMedCrossRefGoogle Scholar
  113. 113.
    Wood IS, Trayhurn P (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89:3–9PubMedCrossRefGoogle Scholar
  114. 114.
    Woods RJ, Grossman A, Saphier P, Kennedy K, Ur E, Behan D, Potter E, Vale W, Lowry PJ (1994) Association of human corticotropin-releasing hormone to its binding protein in blood may trigger clearance of the complex. J Clin Endocr Metab 78:73–76PubMedCrossRefGoogle Scholar
  115. 115.
    Wu G, Imhoff-Kunsch B, Girard AW (2012) Biological mechanisms for nutritional regulation of maternal health and fetal development. Paediatr Perinat Epidemiol 26:4–26PubMedCrossRefGoogle Scholar
  116. 116.
    Wyrwoll CS, Kerrigan D, Holmes MC, Seckl JR, Drake AJ (2012) Altered placental methyl donor transport in the dexamethasone programmed rat. Placenta 33:220–223PubMedCrossRefGoogle Scholar
  117. 117.
    Xu C, Gao L, You X, Dai L, Li Y, Gu H, Slater DM, Olson DM, Ni X (2011) CRH acts on CRH-R1 and -R2 to differentially modulate the expression of large-conductance calcium-activated potassium channels in human pregnant myometrium. Endocrinology 152:4406–4417PubMedCrossRefGoogle Scholar
  118. 118.
    Zhao FQ, Keating AF (2007) Functional properties and genomics of glucose transporters. Curr Genomics 8:113–128PubMedCrossRefGoogle Scholar

Copyright information

© University of Navarra 2012

Authors and Affiliations

  1. 1.School of Biological SciencesUniversity of SydneyCamperdownAustralia

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