Skip to main content
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2015 Mar 2;31(3):338–350. doi: 10.1007/s12264-014-1508-2

Hypothalamic-pituitary-adrenal axis function during perinatal depression

Phillipe Leff Gelman 1,, Mónica Flores-Ramos 2,3, Margarita López-Martínez 1, Carlos Cruz Fuentes 3, Juan Pablo Reyes Grajeda 4
PMCID: PMC5563683  PMID: 25732527

Abstract

Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis is an important pathological finding in pregnant women exhibiting major depressive disorder. They show high levels of cortisol pro-inflammatory cytokines, hypothalamic-pituitary peptide hormones and catecholamines, along with low dehydroepiandrosterone levels in plasma. During pregnancy, the TH2 balance together with the immune system and placental factors play crucial roles in the development of the fetal allograft to full term. These factors, when altered, may generate a persistent dysfunction of the HPA axis that may lead to an overt transfer of cortisol and toxicity to the fetus at the expense of reduced activity of placental 11β-hydroxysteroid dehydrogenase type 2. Epigenetic modifications also may contribute to the dysregulation of the HPA axis. Affective disorders in pregnant women should be taken seriously, and therapies focused on preventing the deleterious effects of stressors should be implemented to promote the welfare of both mother and baby.

Keywords: brain, depression, neuroendocrine, pregnancy, stress, glucocorticoids

References

  • [1].Harvey M, Belleau P, Barden N. Gene interactions in depression: pathways out of darkness. Trends Genet. 2007;23:547–556. doi: 10.1016/j.tig.2007.08.011. [DOI] [PubMed] [Google Scholar]
  • [2].Leff P, Hernández-Gutiérrez ME, Becerril LE, Martínez C, Téllez-Santillán C, Pérez-Tapia M, et al. The neuroendocrine network in stress-inducing mood disorders. Open Neuroendocrinol J. 2010;3:180–207. [Google Scholar]
  • [3].McFarlane A, Clark CR, Bryant RA, Williams LM, Niaura R, Paul RH, et al. The impact of early life stress on psychophysiological, personality and behavioral measures in 740 non-clinical subjects. J Integr Neurosci. 2005;4:27–40. doi: 10.1142/s0219635205000689. [DOI] [PubMed] [Google Scholar]
  • [4].Heim C, Newport DJ, Wagner D, Wilcox MM, Miller AH, Nemeroff CB. The role of early adverse experience and adulthood stress in the prediction of neuroendocrine stress reactivity in women: a multiple regression analysis. Depress Anxiety. 2002;15:117–125. doi: 10.1002/da.10015. [DOI] [PubMed] [Google Scholar]
  • [5].Meltzer-Brody S. New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum. Dialogues Clin Neurosci. 2011;13:89–100. doi: 10.31887/DCNS.2011.13.1/smbrody. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Fishell A. Drugs in pregnancy and lactation symposium: depression and anxiety in pregnancy. J Popul Ther Clin Pharmacol. 2010;17:e363–e369. [PubMed] [Google Scholar]
  • [7].Henry AL, Beach AJ, Stowe ZN, Newport DJ. The fetus and maternal depression: implications for antenatal treatment guidelines. Clin Obstet Gynecol. 2004;4:535–546. doi: 10.1097/01.grf.0000135341.48747.f9. [DOI] [PubMed] [Google Scholar]
  • [8].Dunkel Schetter C, Tanner L. Anxiety, depression and stress in pregnancy: implications for mothers, children, research, and practice. Curr Opin Psychiatry. 2012;25:141–148. doi: 10.1097/YCO.0b013e3283503680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Dayan J, Creveuil C, Dreyfus M, Herlicoviez M, Baleyte JM, O’Keane V. Developmental model of depression applied to prenatal depression: role of present and past life events, past emotional disorders and pregnancy stress. PLoS One. 2010;5:e12942. doi: 10.1371/journal.pone.0012942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Kammerer M, Taylor A, Glover V. The HPA axis and perinatal depression: a hypothesis. Arch Womens Ment Health. 2006;9:187–196. doi: 10.1007/s00737-006-0131-2. [DOI] [PubMed] [Google Scholar]
  • [11].Guerry JD, Hastings PD. In search of HPA axis dysregulation in child and adolescent depression. Clin Child FamPsychol Rev. 2011;14:135–160. doi: 10.1007/s10567-011-0084-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Feldman S, Weidenfeld The excitatory effects of the amygdala on hypothalamus-pituitary-adrenocortical responses are mediated by hypothalamic norepinephrine, serotonin, and CRF-41. Brain Res Bull. 1998;45:389–393. doi: 10.1016/s0361-9230(97)00384-5. [DOI] [PubMed] [Google Scholar]
  • [13].Nemeroff CB. Understanding the pathophysiology of postpartum depression: implications for the development of novel treatments. Neuron. 2008;59:185–186. doi: 10.1016/j.neuron.2008.07.015. [DOI] [PubMed] [Google Scholar]
  • [14].Ehlert U, Gaab J, Heinrichs M. Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: The role of the hypothalamus-pituitary-adrenal axis. Biol Psychol. 2001;57:141–152. doi: 10.1016/s0301-0511(01)00092-8. [DOI] [PubMed] [Google Scholar]
  • [15].Stokes PE, Sikes CR. Hypothalamic-pituitary-adrenal axis in psychiatric disorders. Ann Rev Med. 1991;42:519–531. doi: 10.1146/annurev.me.42.020191.002511. [DOI] [PubMed] [Google Scholar]
  • [16].Rubin RT, Poland RE, Lesser IM, Winston RA, Blodgett AL. Neuroendocrine aspects of primary endogenous depression. I. Cortisol secretory dynamics in patients and matched controls. Arch Gen Psychiatry. 1987;44:328–336. doi: 10.1001/archpsyc.1987.01800160032006. [DOI] [PubMed] [Google Scholar]
  • [17].Young E, Korszun A. Psychoneuroendocrinology of depression: Hypothalamic-pituitary-gonadal axis. Psychiatr Clin North Am. 1998;21:309–323. doi: 10.1016/s0193-953x(05)70007-1. [DOI] [PubMed] [Google Scholar]
  • [18].Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;341:13–25. doi: 10.1016/s0896-6273(02)00653-0. [DOI] [PubMed] [Google Scholar]
  • [19].Gurguis GN, Meador-Woodruff JH, Haskett RF, Greden JF. Multiplicity of depressive episodes: Phenomenological and neuroendocrine correlates. Biol Psychiatry. 1990;27:1156–1164. doi: 10.1016/0006-3223(90)90052-4. [DOI] [PubMed] [Google Scholar]
  • [20].Pruessner M, Hellhammer DH, Pruessner JC, Lupien SJ. Self-reported depressive symptoms and stress levels in healthy young men: associations with the cortisol response to awakening. Psychosom Med. 2003;65:92–99. doi: 10.1097/01.psy.0000040950.22044.10. [DOI] [PubMed] [Google Scholar]
  • [21].Nemeroff CB. The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol Psychiatry. 1996;1:336–342. [PubMed] [Google Scholar]
  • [22].Southwick SM, Vythilingam M, Charney DS. The psychobiology of depression and resilience to stress: implications for prevention and treatment. Annu Rev Clin Psychol. 2005;1:255–291. doi: 10.1146/annurev.clinpsy.1.102803.143948. [DOI] [PubMed] [Google Scholar]
  • [23].Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000;23:477–501. doi: 10.1016/S0893-133X(00)00159-7. [DOI] [PubMed] [Google Scholar]
  • [24].van Rossum EF, Binder EB, Majer M, Koper JW, Ising M, Modell S, et al. Polymorphisms of the glucocorticoid receptor gene and major depression. Biol Psychiatry. 2006;59:681–688. doi: 10.1016/j.biopsych.2006.02.007. [DOI] [PubMed] [Google Scholar]
  • [25].Gotlib IH, Hamilton JP. Neuroimaging and depression: Current status and unresolved issues. Curr Directions Psychol Sci. 2008;17:159–163. [Google Scholar]
  • [26].Seminowicz DA, Mayberg HS, Mcintosh AR, Goldapple K, Kennedy S, Segal Z, et al. Limbic-frontal circuitry in major depression: a path modeling metanalysis. Neuroimage. 2004;22:409–418. doi: 10.1016/j.neuroimage.2004.01.015. [DOI] [PubMed] [Google Scholar]
  • [27].Bloch M, Daly RC, Rubinow DR. Endocrine factors in the etiology of postpartum depression. Comp Psychiatry. 2003;44:234–246. doi: 10.1016/S0010-440X(03)00034-8. [DOI] [PubMed] [Google Scholar]
  • [28].Bloch M, Rubinow DR, Schmidt PJ, Lotsikas A, Chrousos GP, Cizza G. Cortisol response to ovine corticotrophin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab. 2005;90:695–699. doi: 10.1210/jc.2004-1388. [DOI] [PubMed] [Google Scholar]
  • [29].Mastorakos G, Ilias I. Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum. Ann N Y Acad Sci. 2003;997:136–149. doi: 10.1196/annals.1290.016. [DOI] [PubMed] [Google Scholar]
  • [30].Nolten WE, Lindheimer MD, Rueckert PA, Oparil S, Ehrlich EN. Diurnal patterns and regulation of cortisol secretion in pregnancy. J Clin Endocrinol Metab. 1980;51:466–472. doi: 10.1210/jcem-51-3-466. [DOI] [PubMed] [Google Scholar]
  • [31].Champagne FA, Meaney MJ. Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biol Psychiatry. 2006;59:1227–1235. doi: 10.1016/j.biopsych.2005.10.016. [DOI] [PubMed] [Google Scholar]
  • [32].Murphy-Eberenz K1, Zandi PP, March D, Crowe RR, Scheftner WA, Alexander M, et al. Is perinatal depression familial? J Affect Disord. 2006;90:49–55. doi: 10.1016/j.jad.2005.10.006. [DOI] [PubMed] [Google Scholar]
  • [33].Jolley SN, Elmore S, Barnard KE, Carr DB. Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum depression. Biological Res Nurs. 2007;8:210–222. doi: 10.1177/1099800406294598. [DOI] [PubMed] [Google Scholar]
  • [34].Gold PW, Gabry KE, Yasuda MR, Chrousos GP. Divergent endocrine abnormalities in melancholic and atypical depression: clinical and pathophysiologic implications. Endocrinol Metabol Clin N Am. 2002;31:37–62. doi: 10.1016/s0889-8529(01)00022-6. [DOI] [PubMed] [Google Scholar]
  • [35].Petraglia F, Imperatore A, Challis JR. Neuroendocrine mechanisms in pregnancy and parturition. Endocr Rev. 2010;31(6):783–816. doi: 10.1210/er.2009-0019. [DOI] [PubMed] [Google Scholar]
  • [36].Zoumakis E, Kalantaridou SN, Makrigiannakis A. CRH-like peptides in human reproduction. Curr Med Chem. 2009;16:4230–4235. doi: 10.2174/092986709789578204. [DOI] [PubMed] [Google Scholar]
  • [37].Lovejoy DA, Balment RJ. Evolution and physiology of the corticotrophin-releasing factor (CRF) family of neuropeptides in vertebrates. Gen Comp Endocrinol. 1999;115:1–22. doi: 10.1006/gcen.1999.7298. [DOI] [PubMed] [Google Scholar]
  • [38].Watts AG. The impact of physiological stimuli on the expression of corticotrophin-releasing hormone (CRH) and other neuropeptide genes. Front Neuroendocrinol. 1996;17:281–326. doi: 10.1006/frne.1996.0008. [DOI] [PubMed] [Google Scholar]
  • [39].Arai M, Assil IQ, Abou-Samra AB. Characterization of three corticotrophin-releasing factor receptors in catfish: A novel third receptor is predominantly expressed in pituitary and urophysis. Endocrinology. 2001;142:446–454. doi: 10.1210/endo.142.1.7879. [DOI] [PubMed] [Google Scholar]
  • [40].Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotrophin and -endorphin. Science. 1981;213:1394–1397. doi: 10.1126/science.6267699. [DOI] [PubMed] [Google Scholar]
  • [41].Montecucchi PC, Anastasi A, de Castiglione R, Erspamer V. Isolation and amino acid composition of sauvagine. An active polypeptide from methanol extracts of the skin of the South American frog Phyllomedusa sauvagei. Int J Pept Protein Res. 1980;16:191–199. [PubMed] [Google Scholar]
  • [42].Ichikawa T, McMaster D, Lederis K, Kobayashi H. Isolation and amino acid sequence of urotensin-I, a vasoactive and ACTH-releasing neuropeptide from the carp (Cyprinuscarpio) Peptides. 1982;3:859–867. doi: 10.1016/0196-9781(82)90028-6. [DOI] [PubMed] [Google Scholar]
  • [43].Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, et al. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotrophin releasing factor. Nature. 1995;378:287–292. doi: 10.1038/378287a0. [DOI] [PubMed] [Google Scholar]
  • [44].Hsu SY, Hsueh AJ. Human stresscopin and stresscopinrelated peptide are selective ligands for the type 2 corticotrophin-releasing hormone receptor. Nat Med. 2001;7:605–611. doi: 10.1038/87936. [DOI] [PubMed] [Google Scholar]
  • [45].Vitoratos N, Papatheodorou DC, Kalantaridou SN, Mastorakos G. “Reproductive” corticotrophin-releasing hormone. Ann N Y Acad Sci. 2006;1092:310–318. doi: 10.1196/annals.1365.029. [DOI] [PubMed] [Google Scholar]
  • [46].Petraglia F, Florio P, Gallo R, Simoncini T, Saviozzi M, Di Blasio AM, et al. Human placenta and fetal membranes express human urocortin mRNA and peptide. J Clin Endocrinol Metab. 1996;81:3807–3810. doi: 10.1210/jcem.81.10.8855842. [DOI] [PubMed] [Google Scholar]
  • [47].Imperatore A, Florio P, Torres PB, Torricelli M, Galleri L, Toti P, et al. Urocortin 2 and urocortin 3 are expressed by the human placenta, deciduas, and fetal membranes. Am J Obstet Gynecol. 2006;195:288–295. doi: 10.1016/j.ajog.2005.12.048. [DOI] [PubMed] [Google Scholar]
  • [48].Swanson LW, Sawchenko PE, Lind RW, Rho JH. The CRH motoneuron: differential peptide regulation in neuronswith possible synaptic, paracrine, and endocrine outputs. Ann NY Acad Sci. 1987;512:12–23. doi: 10.1111/j.1749-6632.1987.tb24948.x. [DOI] [PubMed] [Google Scholar]
  • [49].Koshimizu TA, Nasa Y, Tanoue A, Oikawa R, Kawahara Y, Kiyono Y, et al. V1a vasopression receptors maintain normal blood pressure by regulation circulating blood volume and baroreflex sensitivity. Proc Natl Acad Sci U S A. 2006;103:7807–7812. doi: 10.1073/pnas.0600875103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [50].Vantyghem MC, Balavoine AS, Wémeau JL, Douillard C. Hyponatremia and antidiuresis syndrome. Ann Endocrinol (Paris) 2011;72:500–512. doi: 10.1016/j.ando.2011.10.001. [DOI] [PubMed] [Google Scholar]
  • [51].Jard S, Barberis C, Audigier S, Tribollet E. Neurohypophyseal hormone receptor systems in brain and periphery. Prog Brain Res. 1987;72:173–187. doi: 10.1016/s0079-6123(08)60206-x. [DOI] [PubMed] [Google Scholar]
  • [52].Thibonnier M, Coles P, Thibonnier A, Shoham M. Molecular pharmacology and modeling of vasopressin receptors. Prog Brain Res. 2002;139:179–196. doi: 10.1016/s0079-6123(02)39016-2. [DOI] [PubMed] [Google Scholar]
  • [53].Roper J, O’Carroll AM, Young W, 3rd, Lolait S. The vasopressin Avpr1b receptor: molecular and pharmacological studies. Stress. 2011;14:98–115. doi: 10.3109/10253890.2010.512376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [54].Knepper MA. Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. Am J Physiol. 1997;272:F3–12. doi: 10.1152/ajprenal.1997.272.1.F3. [DOI] [PubMed] [Google Scholar]
  • [55].Antoni F. Vasopressinergic control of pituitary adrenocorticotrophin secretion comes of age. Front Neuroendocrinol. 1993;14:76–122. doi: 10.1006/frne.1993.1004. [DOI] [PubMed] [Google Scholar]
  • [56].Whitnall M. Stress selectively activates the vasopressin-containing subset of corticotrophin-releasing hormoneneurons. Neuroendocrinology. 1989;50:702–707. doi: 10.1159/000125302. [DOI] [PubMed] [Google Scholar]
  • [57].Derick S, Pena A, Durroux T, Wagnon J, Serradeil-Le Gal C, Hibert M, et al. Key amino acid located within the transmembrane domains 5 and 7 account for the pharmacological specificity of the human V1b vasopressin receptor. Mol Endocrinol. 2004;18:2777–2789. doi: 10.1210/me.2004-0124. [DOI] [PubMed] [Google Scholar]
  • [58].Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci. 2008;31:464–468. doi: 10.1016/j.tins.2008.06.006. [DOI] [PubMed] [Google Scholar]
  • [59].Gillies GE, Linton EA, Lowry PJ. Corticotrophin releasing activity of the new CRF is potentiated several times by vasopressin. Nature. 1982;299:355–357. doi: 10.1038/299355a0. [DOI] [PubMed] [Google Scholar]
  • [60].Livesey JH, Evans MJ, Mulligan R, Donald RA. Interactions of CRH, AVP and cortisol in the secretion of ACTH from perifused equine anterior pituitary cells: “permissive” roles for cortisol and CRH. Endocr Res. 2000;263:445–463. doi: 10.3109/07435800009066179. [DOI] [PubMed] [Google Scholar]
  • [61].Gispen-de Wied CC, Westenberg HG, Koppeschaar HP, Thijssen JH, van Ree JM. Stimulation of the pituitary-adrenal axis with a low dose [Arg8]-vasopressin in depressed patients and healthy subjects. Eur Neuropsychopharmacol. 1992;2:411–419. doi: 10.1016/0924-977x(92)90003-q. [DOI] [PubMed] [Google Scholar]
  • [62].Lolait SJ, Stewart LQ, Jessop DS, Young WS, 3rd, O’Carroll AM. The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin Avpr1b receptors. Endocrinology. 2007;148:849–856. doi: 10.1210/en.2006-1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [63].Timpl P, Spanagel R, Sillaber I, Kresse A, Reul JM, Stalla GK, et al. Impaired stress response and reduced anxiety in mice lacking a functional corticotrophin releasing hormone receptor. Nat Genetics. 1998;19:162–166. doi: 10.1038/520. [DOI] [PubMed] [Google Scholar]
  • [64].Smith GW, Aubry JM, Dellu F, Contarino A, Bilezikjian LM, Gold LH, et al. Corticotrophin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron. 1998;20:1093–1102. doi: 10.1016/s0896-6273(00)80491-2. [DOI] [PubMed] [Google Scholar]
  • [65].Müller MB, Landgraf R, Preil J, Sillaber I, Kresse AE, Keck ME, et al. Selective activation of the hypothalamic vasopressinergic system in mice deficient for the corticotrophin-releasing hormone receptor 1 is dependent on glucocorticoids. Endocrinology. 2000;141:4262–4269. doi: 10.1210/endo.141.11.7767. [DOI] [PubMed] [Google Scholar]
  • [66].Tanoue A, Ito S, Honda K, Oshikawa S, Kitagawa Y, Koshimizu TA, et al. The vasopressin Avpr1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J Clin Invest. 2004;113:302–309. doi: 10.1172/JCI19656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [67].Legros JJ. Inhibitory effect of oxytocin on corticotroph function in humans: are vasopressin and oxytocin ying-yang neurohormones? Psychoneuroendocrinology. 2001;26:649–655. doi: 10.1016/s0306-4530(01)00018-x. [DOI] [PubMed] [Google Scholar]
  • [68].Aguilera G, Rabadan-Diehl C. Vasopressinergic regulation of the hypothalamic-pituitary-adrenal axis: implications for stress adaptation. Regul Pept. 2000;96:23–29. doi: 10.1016/s0167-0115(00)00196-8. [DOI] [PubMed] [Google Scholar]
  • [69].Pariante CM. The glucocorticoid receptor: part of the solution or part of the problem? Psychopharmacol. 2006;20:79–84. doi: 10.1177/1359786806066063. [DOI] [PubMed] [Google Scholar]
  • [70].Lim MM, Young LJ. Neuropeptidergic regulation of affiliative behaviorand social boding in animals. Horm Behav. 2006;50:506–517. doi: 10.1016/j.yhbeh.2006.06.028. [DOI] [PubMed] [Google Scholar]
  • [71].Hodes GE. Sex, stress, and epigenetics: regulation of behavior in animal models of mood disorders. Biol Sex Differ. 2013;21:1. doi: 10.1186/2042-6410-4-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [72].Elenkov IJ, Chrousos GP. Stress, cytokine patterns and susceptibility to disease. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13:583–595. doi: 10.1053/beem.1999.0045. [DOI] [PubMed] [Google Scholar]
  • [73].Turnbull AV, Rivier CL. Regulation of the hypothalamicpituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev. 1999;79:1–71. doi: 10.1152/physrev.1999.79.1.1. [DOI] [PubMed] [Google Scholar]
  • [74].Meaney MJ, Diorio J, Francis D, Widdowson J, LaPlante P, Caldji C, et al. Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev Neurosci. 1996;18:49–72. doi: 10.1159/000111395. [DOI] [PubMed] [Google Scholar]
  • [75].Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59:279–89. doi: 10.1016/j.yhbeh.2010.06.007. [DOI] [PubMed] [Google Scholar]
  • [76].Kalantaridou SN, Zoumakis E, Makrigiannakis A, Lavasidis LG, Vrekoussis T, Chrousos GP. Corticotrophin-releasing hormone, stress and human reproduction: an update. J Reprod Immunol. 2010;851:33–39. doi: 10.1016/j.jri.2010.02.005. [DOI] [PubMed] [Google Scholar]
  • [77].Seckl JR. 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol. 2004;4:597–602. doi: 10.1016/j.coph.2004.09.001. [DOI] [PubMed] [Google Scholar]
  • [78].Draper N, Stewart PM. 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. J Endocrinol. 2005;186(2):251–271. doi: 10.1677/joe.1.06019. [DOI] [PubMed] [Google Scholar]
  • [79].Kotelevtsev YV, Holmes MC, Burchell A, Houston PM, Scholl D, Jamieson PM, et al. 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid inducible responses and resist hyperglycaemia on obesity and stress. Proc Natl Acad Sci U S A. 1997;94:14924–14929. doi: 10.1073/pnas.94.26.14924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [80].Seckl JR, Walker BR. 11beta-hydroxysteroid dehydrogenase type 1-a tissue-specific amplifier of glucocorticoid action. Endocrinology. 2001;142:1371–1376. doi: 10.1210/endo.142.4.8114. [DOI] [PubMed] [Google Scholar]
  • [81].Moisan M-P, Seckl JR, Edwards CRW. 11b-Hydroxysteroid dehydrogenase bioactivity and messenger RNA expression in rat forebrain: localization in hypothalamus, hippocampus and cortex. Endocrinology. 1990;127:1450–1455. doi: 10.1210/endo-127-3-1450. [DOI] [PubMed] [Google Scholar]
  • [82].Anacker C, Zunszain PA, Carvalho LA, Pariante CM. The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology. 2011;36:415–425. doi: 10.1016/j.psyneuen.2010.03.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [83].Krishnan V, Nestler EJ. Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry. 2010;167:1305–1320. doi: 10.1176/appi.ajp.2009.10030434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [84].Tasker JG, Di S, Malcher-Lopes R. Minireview: rapid glucocorticoid signaling via membrane-associated receptors. Endocrinology. 2006;147:5549–5556. doi: 10.1210/en.2006-0981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [85].Wyrwoll CS, Holmes MC, Seckl JR. 11β-hydroxysteroid dehydrogenases and the brain: from zero to hero, a decade of progress. Front Neuroendocrinol. 2011;32:265–286. doi: 10.1016/j.yfrne.2010.12.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [86].de Kloet ER, Karst H, Joëls M. Corticosteroid hormones in the central stress response: quick-and-slow. Front Neuroendocrinol. 2008;29:268–272. doi: 10.1016/j.yfrne.2007.10.002. [DOI] [PubMed] [Google Scholar]
  • [87].Geerling JC, Loewy AD. Aldosterone in the brain. Am J Physiol Renal Physiol. 2009;297:F559–F576. doi: 10.1152/ajprenal.90399.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [88].Funder JW. Mineralocorticoid receptors in the central nervous system. J Steroid Biochem Mol Biol. 1996;56:179–183. doi: 10.1016/0960-0760(95)00235-9. [DOI] [PubMed] [Google Scholar]
  • [89].Hinz B, Hirschelmann R. Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats. Pharm Res. 2000;17:1273–1277. doi: 10.1023/a:1026499604848. [DOI] [PubMed] [Google Scholar]
  • [90].Keller-Wood ME, Dallman MF. Corticosteroid inhibition of ACTH secretion. Endocr Rev. 1984;5:1–24. doi: 10.1210/edrv-5-1-1. [DOI] [PubMed] [Google Scholar]
  • [91].Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med. 1998;129:229–240. doi: 10.7326/0003-4819-129-3-199808010-00012. [DOI] [PubMed] [Google Scholar]
  • [92].Aguilera G, Rabadan-Diehl C. Regulation of vasopressin Avpr1b receptors in the anterior pituitary gland of the rat. Exp Physiol. 2000;85(Spec):19S–26S. doi: 10.1111/j.1469-445x.2000.tb00004.x. [DOI] [PubMed] [Google Scholar]
  • [93].Wu Z, Ji H, Hassan A, Aguilera G, Sandberg K. Regulation of pituitary corticotrophin releasing factor type-1 receptor mRNA binding proteins by modulation of the hypothalamic-pituitaryadrenal axis. J Neuroendocrinol. 2004;16:214–220. doi: 10.1111/j.0953-8194.2004.01153.x. [DOI] [PubMed] [Google Scholar]
  • [94].Makino S, Schulkin J, Smith MA, Pacák K, Palkovits M, Gold PW. Regulation of corticotrophin-releasing hormone receptor messenger ribonucleic acid in the rat brain and pituitary by glucocorticoids and stress. Endocrinology. 1995;136:4517–4525. doi: 10.1210/endo.136.10.7664672. [DOI] [PubMed] [Google Scholar]
  • [95].Rabadan-Diehl C, Makara G, Kiss A, Lolait S, Zelena D, Ochedalski T, et al. Regulation of pituitary Avpr1b vasopressin receptor messenger ribonucleic acid by adrenalectomy and glucocorticoid administration. Endocrinology. 1997;138:5189–5194. doi: 10.1210/endo.138.12.5580. [DOI] [PubMed] [Google Scholar]
  • [96].Verkuyl JM, Hemby SE, Joëls M. Chronic stress attenuates GABAergic inhibition and alters gene expression of parvocellular neurons in rat hypothalamus. Eur J Neurosci. 2004;20:1665–1673. doi: 10.1111/j.1460-9568.2004.03568.x. [DOI] [PubMed] [Google Scholar]
  • [97].Verkuyl JM, Karst H, Joëls M. GABAergic transmission in the rat paraventricular nucleus of the hypothalamus is suppressed by corticosterone and stress. Eur J Neurosci. 2005;21:113–121. doi: 10.1111/j.1460-9568.2004.03846.x. [DOI] [PubMed] [Google Scholar]
  • [98].Miklós IH, Kovács KJ. GABAergic innervation of corticotrophin-releasing hormone (CRH)-secreting parvocellular neurons and its plasticity as demonstrated by quantitative immunoelectron microscopy. Neuroscience. 2002;113:581–592. doi: 10.1016/s0306-4522(02)00147-1. [DOI] [PubMed] [Google Scholar]
  • [99].Zhu CB, Carneiro AM, Dostmann WR, Hewlett WA, Blakely RD. p38 MAPK activation elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process. J Biol Chem. 2005;280:15649–15658. doi: 10.1074/jbc.M410858200. [DOI] [PubMed] [Google Scholar]
  • [100].Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling M. Multiple actions of steroid hormones-a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52:513–556. [PubMed] [Google Scholar]
  • [101].Newton R. Molecular mechanisms of glucocorticoid action: what is important? Thorax. 2000;55:603–613. doi: 10.1136/thorax.55.7.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [102].Seckl JR. Prenatal glucocorticoids and long-term programming. Eur J Endocrinol. 2004;151(Suppl3):U49–U62. doi: 10.1530/eje.0.151u049. [DOI] [PubMed] [Google Scholar]
  • [103].Ward RM. Pharmacologic enhancement of fetal lung maturation. Clin Perinatol. 1994;21:523–542. [PubMed] [Google Scholar]
  • [104].Cole TJ. Cloning of the mouse 11beta-hydroxysteroid dehydrogenase type 2 gene: tissue specific expression and localization in distal convoluted tubules and collecting ducts of the kidney. Endocrinology. 1995;136:4693–4696. doi: 10.1210/endo.136.10.7664690. [DOI] [PubMed] [Google Scholar]
  • [105].Speirs H, Seckl J, Brown R. Ontogeny of glucocorticoid receptor and 11b-hydroxysteroid dehydrogenase type 1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development. J Endocrinol. 2004;181:105–116. doi: 10.1677/joe.0.1810105. [DOI] [PubMed] [Google Scholar]
  • [106].Sun K, Yang K, Challis JRG. Differential expression of 11betahydroxysteroid dehydrogenase types 1 and 2 in human placenta and fetal membranes. J Clin Endocrinol Metab. 1997;82:300–305. doi: 10.1210/jcem.82.1.3681. [DOI] [PubMed] [Google Scholar]
  • [107].Stewart PM, Rogerson FM, Mason JI. Type 2 11b-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. 1995;80:885–890. doi: 10.1210/jcem.80.3.7883847. [DOI] [PubMed] [Google Scholar]
  • [108].McTernan CL, Draper N, Nicholson H, Chalder SM, Driver P, Hewison M, et al. Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms. J Clin Endocrinol Metab. 2001;86:4979–4983. doi: 10.1210/jcem.86.10.7893. [DOI] [PubMed] [Google Scholar]
  • [109].Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A. 1996;93:3908–3913. doi: 10.1073/pnas.93.9.3908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [110].Fernandez-Guasti A, Fiedler JL, Herrera L, Handa RJ. Sex, stress and mood disorders: at the intersection of adrenal and gonadal hormones. Horm Metab Res. 2012;44:607–618. doi: 10.1055/s-0032-1312592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [111].Forbes K, Westwood M. Maternal growth factor regulation of human placental development and fetal growth. J Endocrinol. 2010;207:1–16. doi: 10.1677/JOE-10-0174. [DOI] [PubMed] [Google Scholar]
  • [112].Mastorakos G, Scopa CD, Kao LC, Vryonidou A, Friedman TC, Kattis D, et al. Presence of immunoreactive corticotrophin-releasing hormone in human endometrium. J Clin Endocrinol Metab. 1996;81:1046–1050. doi: 10.1210/jcem.81.3.8772574. [DOI] [PubMed] [Google Scholar]
  • [113].Makrigiannakis A1, Zoumakis E, Margioris AN, Theodoropoulos P, Stournaras C, Gravanis A. The corticotrophin-releasing hormone (CRH) in normal and tumoral epithelial cells of human endometrium. J Clin Endocrinol Metab. 1995;80:185–189. doi: 10.1210/jcem.80.1.7829610. [DOI] [PubMed] [Google Scholar]
  • [114].Di Blasio AM, Pecori Giraldi F, Viganò P, Petraglia F, Vignali M, Cavagnini F. Expression of corticotrophin-releasing hormone and its R1 receptor in human endometrial stromal cells. J Clin Endocrinol Metab. 1997;82:1594–1597. doi: 10.1210/jcem.82.5.3923. [DOI] [PubMed] [Google Scholar]
  • [115].Gravanis A, Makrigiannakis A, Zoumakis E, Margioris AN. Endometrial and myometrial corticotrophin-releasing hormone (CRH): its regulation and possible roles. Peptides. 2001;22:785–793. doi: 10.1016/s0196-9781(01)00392-8. [DOI] [PubMed] [Google Scholar]
  • [116].Makrigiannakis A, Zoumakis E, Kalantaridou S, Coutifaris C, Margioris AN, Coukos G, et al. Corticotrophin-releasing hormone promotes blastocyst implantation and early maternal tolerance. Nat Immunol. 2001;2:1018–1024. doi: 10.1038/ni719. [DOI] [PubMed] [Google Scholar]
  • [117].Linton EA, Perkins AV, Woods RJ, Eben F, Wolfe CD, Behan DP, et al. Corticotrophin releasing hormone-binding protein (CRH-BP): plasma levels decrease during the third trimester of normal human pregnancy. J Clin Endocrinol Metab. 1993;76:260–262. doi: 10.1210/jcem.76.1.8421097. [DOI] [PubMed] [Google Scholar]
  • [118].Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med. 1998;129:229–240. doi: 10.7326/0003-4819-129-3-199808010-00012. [DOI] [PubMed] [Google Scholar]
  • [119].Goland RS, Tropper PJ, Warren WB, Stark RI, Jozak SM, Conwell IM. Concentrations of corticotrophin-releasing hormone in the umbilical-cord blood of pregnancies complicated by pre-eclampsia. Reprod Fertil Dev. 1995;7:1227–1230. doi: 10.1071/rd9951227. [DOI] [PubMed] [Google Scholar]
  • [120].McLean M, Bisits A, Davies J, Woods R, Lowry P, Smith R. A placental clock controlling the length of human pregnancy. Nat Med. 1995;1:460–463. doi: 10.1038/nm0595-460. [DOI] [PubMed] [Google Scholar]
  • [121].Wyrwoll CS, Holmes MC. Prenatal excess glucocorticoid exposure and adult affective disorders: a role for serotonergic and catecholamine pathways. Neuroendocrinol. 2012;95:47–55. doi: 10.1159/000331345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [122].Pavón L, Sandoval-López G, Eugenia Hernández M, Loría F, Estrada I, Pérez M, et al. Th2 cytokine response in Major Depressive Disorder patients before treatment. J Neuroimmunol. 2006;172:156–165. doi: 10.1016/j.jneuroim.2005.08.014. [DOI] [PubMed] [Google Scholar]
  • [123].O’Donnell KJ, Bugge Jensen A, Freeman L, Khalife N, O’Connor TG, Glover V. Maternal prenatal anxiety and downregulation of placental 11β-HSD2. Psychoneuroendocrinology. 2012;37:818–826. doi: 10.1016/j.psyneuen.2011.09.014. [DOI] [PubMed] [Google Scholar]
  • [124].Sun H, Kennedy PJ, Nestler EJ. Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacology. 2013;38:124–137. doi: 10.1038/npp.2012.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [125].Feng J, Fan G. The role of DNA methylation in the central nervous system and neuropsychiatric disorders. Int Rev Neurobiol. 2009;89:67–84. doi: 10.1016/S0074-7742(09)89004-1. [DOI] [PubMed] [Google Scholar]
  • [126].Mastorakos G, Ilias I. Maternal and fetal hypothalamicpituitary-adrenal axes during pregnancy and postpartum. Ann NY Acad Sci. 2003;997:136–149. doi: 10.1196/annals.1290.016. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES