Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

World Journal of Gastroenterology

Volumn 20, Issue 22, 2014, Pages 6725-6743

  Meleine, Mathieu ^a,b   Matricon, Julien ^b,c  

^a UNIVERSITÉ DE ROUEN   (France)

^b UNIVERSITÉ CLERMONT AUVERGNE   (France)

^c Mays Cancer Center at UT Health San Antonio   (United States)

Author keywords

Gender; Gut; Immune activation; Irritable bowel syndrome; Neurosensitization; Pathophysiology; Permeabilization; Sensori motricity; Sex hormones; Stress

Indexed keywords

CHOLECYSTOKININ; CORTICOTROPIN RELEASING FACTOR; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; HYDROCORTISONE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; OVARY PEPTIDE HORMONE; OXYTOCIN; PROGESTERONE; PROGESTERONE RECEPTOR; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; SEROTONIN; SEX HORMONE; TESTOSTERONE;

ARTICLE; CONSTIPATION; DEFECATION HABIT; ELECTROENCEPHALOGRAM; GASTROINTESTINAL MOTILITY; HUMAN; HYPERSENSITIVITY; IMMUNE RESPONSE; IMMUNOMODULATION; INTESTINE MUCOSA PERMEABILITY; INTESTINE TRANSIT TIME; IRRITABLE COLON; MENSTRUAL CYCLE; NONHUMAN; PATHOPHYSIOLOGY; PEPTIDERGIC NERVOUS SYSTEM; RISK FACTOR; SENSORIMOTOR FUNCTION; SEX DIFFERENCE; SMOOTH MUSCLE CONTRACTILITY; SPINAL GANGLION; STRESS; VISCERAL PAIN; ANIMAL; BIOLOGICAL MODEL; FEMALE; GASTROINTESTINAL TRACT; HYPERALGESIA; IMMUNOLOGY; IRRITABLE BOWEL SYNDROME; MALE; METABOLISM; OVARY; PAIN THRESHOLD; PROGNOSIS; SEVERITY OF ILLNESS INDEX; SEX RATIO;

ANIMALS; FEMALE; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRACT; GONADAL STEROID HORMONES; HUMANS; HYPERALGESIA; IRRITABLE BOWEL SYNDROME; MALE; MODELS, BIOLOGICAL; OVARY; PAIN THRESHOLD; PROGNOSIS; RISK FACTORS; SEVERITY OF ILLNESS INDEX; SEX DISTRIBUTION; SEX FACTORS; VISCERAL PAIN;

EID: 84902137205     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i22.6725     Document Type: Article

References (215)

1. Choung RS, Locke GR. Epidemiology of IBS. Gastroenterol Clin North Am 2011; 40: 1-10 [PMID: 21333897 DOI: 10.1016/ j.gtc.2010.12.006]
2. Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R. The burden of selected digestive diseases in the United States. Gastroenterology 2002; 122: 1500-1511 [PMID: 11984534 DOI: 10.1053/gast.2002.32978]
3. Azpiroz F, Bouin M, Camilleri M, Mayer EA, Poitras P, Serra J, Spiller RC. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Motil 2007; 19: 62-88 [PMID: 17280586 DOI: 10.1111/j.1365-2982.2006.00875.x]
4. Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2012; 303: G775-G785 [PMID: 22837345 DOI: 10.1152/ajpgi.00155.2012]
5. Matricon J, Meleine M, Gelot A, Piche T, Dapoigny M, Muller E, Ardid D. Review article: Associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther 2012; 36: 1009-1031 [PMID: 23066886 DOI: 10.1111/apt.12080]
6. Chial HJ, Camilleri M. Gender differences in irritable bowel syndrome. J Gend Specif Med 2002; 5: 37-45 [PMID: 12078061]
7. McCarberg BH. Clinical overview of fibromyalgia. Am J Ther 2012; 19: 357-368 [PMID: 21326083 DOI: 10.1097/ MJT.0b013e3181ff7bee]
8. Lipton RB, Stewart WF, Scher AI. Epidemiology and economic impact of migraine. Curr Med Res Opin 2001; 17 Suppl 1: s4-12 [PMID: 12463270]
9. Flier SN, Rose S. Is functional dyspepsia of particular concern in women? A review of gender differences in epidemiology, pathophysiologic mechanisms, clinical presentation, and management. Am J Gastroenterol 2006; 101: S644-S653 [PMID: 17177870 DOI: 10.1111/j.1572-0241.2006.01015.x]
10. Walker EA, Gelfand AN, Gelfand MD, Green C, Katon WJ. Chronic pelvic pain and gynecological symptoms in women with irritable bowel syndrome. J Psychosom Obstet Gynaecol 1996; 17: 39-46 [PMID: 8860885]
11. Dinos S, Khoshaba B, Ashby D, White PD, Nazroo J, Wessely S, Bhui KS. A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping. Int J Epidemiol 2009; 38: 1554-1570 [PMID: 19349479 DOI: 10.1093/ije/dyp147]
12. Grigoriadis S, Robinson GE. Gender issues in depression. Ann Clin Psychiatry 2007; 19: 247-255 [PMID: 18058282 DOI: 10.1080/10401230701653294]
13. Unruh AM. Gender variations in clinical pain experience. Pain 1996; 65: 123-167 [PMID: 8826503]
14. Hinds JP, Stoney B, Wald A. Does gender or the menstrual cycle affect colonic transit? Am J Gastroenterol 1989; 84: 123-126 [PMID: 2916519]
15. Laessle RG, Tuschl RJ, Schweiger U, Pirke KM. Mood changes and physical complaints during the normal menstrual cycle in healthy young women. Psychoneuroendocrinology 1990; 15: 131-138 [PMID: 2359810]
16. Heitkemper MM, Jarrett M. Pattern of gastrointestinal and somatic symptoms across the menstrual cycle. Gastroenterology 1992; 102: 505-513 [PMID: 1732122]
17. Moore J, Barlow D, Jewell D, Kennedy S. Do gastrointestinal symptoms vary with the menstrual cycle? Br J Obstet Gynaecol 1998; 105: 1322-1325 [PMID: 9883927]
18. Palomba S, Di Cello A, Riccio E, Manguso F, La Sala GB. Ovarian function and gastrointestinal motor activity. Minerva Endocrinol 2011; 36: 295-310 [PMID: 22322653]
19. Altman G, Cain KC, Motzer S, Jarrett M, Burr R, Heitkemper M. Increased symptoms in female IBS patients with dysmenorrhea and PMS. Gastroenterol Nurs 2006; 29: 4-11 [PMID: 16552294]
20. Heitkemper MM, Chang L. Do fluctuations in ovarian hormones affect gastrointestinal symptoms in women with irritable bowel syndrome? Gend Med 2009; 6 Suppl 2: 152-167 [PMID: 19406367 DOI: 10.1016/j.genm.2009.03.004]
21. Heitkemper MM, Jarrett M, Caudell KA, Bond E. Women with gastrointestinal symptoms: implications for nursing research and practice. Gastroenterol Nurs 1993; 15: 226-232 [PMID: 8323989]
22. Jackson NA, Houghton LA, Whorwell PJ, Currer B. Does the menstrual cycle affect anorectal physiology? Dig Dis Sci 1994; 39: 2607-2611 [PMID: 7995186]
23. Heitkemper MM, Cain KC, Jarrett ME, Burr RL, Crowell MD, Woods NF. Relationship of bloating to other GI and menstrual symptoms in women with irritable bowel syndrome. Dig Dis Sci 2004; 49: 88-95 [PMID: 14992441]
24. Okoro NI, Kane SV. Gender-related issues in the female inflammatory bowel disease patient. Expert Rev Gastroenterol Hepatol 2009; 3: 145-154 [PMID: 19351285 DOI: 10.1586/ egh.09.1]
25. Houghton LA, Lea R, Jackson N, Whorwell PJ. The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers. Gut 2002; 50: 471-474 [PMID: 11889064]
26. Sanoja R, Cervero F. Estrogen-dependent changes in visceral afferent sensitivity. Auton Neurosci 2010; 153: 84-89 [PMID: 19631592 DOI: 10.1016/j.autneu.2009.07.001]
27. Teff KL, Alavi A, Chen J, Pourdehnad M, Townsend RR. Muscarinic blockade inhibits gastric emptying of mixednutrient meal: effects of weight and gender. Am J Physiol 1999; 276: R707-R714 [PMID: 10070130]
28. Meier R, Beglinger C, Dederding JP, Meyer-Wyss B, Fumagalli M, Rowedder A, Turberg Y, Brignoli R. Influence of age, gender, hormonal status and smoking habits on colonic transit time. Neurogastroenterol Motil 1995; 7: 235-238 [PMID: 8574912]
29. Wald A, Van Thiel DH, Hoechstetter L, Gavaler JS, Egler KM, Verm R, Scott L, Lester R. Gastrointestinal transit: the effect of the menstrual cycle. Gastroenterology 1981; 80: 1497-1500 [PMID: 7227774]
30. Kamm MA, Farthing MJ, Lennard-Jones JE. Bowel function and transit rate during the menstrual cycle. Gut 1989; 30: 605-608 [PMID: 2731752 DOI: 10.1136/gut.30.5.605]
31. Bovo P, Paola Brunori M, di Francesco V, Frulloni L, Montesi G, Cavallini G. The menstrual cycle has no effect on gastrointestinal transit time. Evaluation by means of the lactulose H2 breath test. Ital J Gastroenterol 1992; 24: 449-451 [PMID: 1421448]
32. Wald A, Van Thiel DH, Hoechstetter L, Gavaler JS, Egler KM, Verm R, Scott L, Lester R. Effect of pregnancy on gastrointestinal transit. Dig Dis Sci 1982; 27: 1015-1018 [PMID: 7140485]
33. Baron TH, Ramirez B, Richter JE. Gastrointestinal motility disorders during pregnancy. Ann Intern Med 1993; 118: 366-375 [PMID: 8257464 DOI: 10.7326/0003-4819-118-5-1993 03010-00008]
34. Wald A. Constipation, diarrhea, and symptomatic hemorrhoids during pregnancy. Gastroenterol Clin North Am 2003; 32: 309-22, vii [PMID: 12635420]
35. Shah S, Hobbs A, Singh R, Cuevas J, Ignarro LJ, Chaudhuri G. Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves. Am J Physiol Regul Integr Comp Physiol 2000; 279: R1478-R1485 [PMID: 11004018]
36. Shah S, Nathan L, Singh R, Fu YS, Chaudhuri G. E2 and not P4 increases NO release from NANC nerves of the gastrointestinal tract: implications in pregnancy. Am J Physiol Regul Integr Comp Physiol 2001; 280: R1546-R1554 [PMID: 11294780]
37. Ryan JP, Bhojwani A. Colonic transit in rats: effect of ovariectomy, sex steroid hormones, and pregnancy. Am J Physiol 1986; 251: G46-G50 [PMID: 3728676]
38. Hogan AM, Kennelly R, Collins D, Baird AW, Winter DC. Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism. Br J Surg 2009; 96: 817-822 [PMID: 19405165 DOI: 10.1002/bjs.6612]
39. Shimomura A, Ohama T, Hori M, Ozaki H. 17Beta-estradiol induces gastrointestinal motility disorder by decreasing CPI-17 phosphorylation via changes in rho-family G-protein Rnd expression in small intestine. J Vet Med Sci 2009; 71: 1591-1597 [PMID: 20046026]
40. Xie D, Chen L, Liu C, Liu K. The inhibitory effects of oxytocin on distal colonic contractile activity in rabbits are enhanced by ovarian steroids. Acta Physiol (Oxf) 2006; 186: 141-149 [PMID: 16497191 DOI: 10.1111/j.1365-201X.2005.01506.x]
41. Xie DP, Chen LB, Liu CY, Liu JZ, Liu KJ. Effect of oxytocin on contraction of rabbit proximal colon in vitro. World J Gastroenterol 2003; 9: 165-168 [PMID: 12508375]
42. Wu CL, Hung CR, Chang FY, Pau KY, Wang JL, Wang PS. Involvement of cholecystokinin receptor in the inhibition of gastric emptying by oxytocin in male rats. Pflugers Arch 2002; 445: 187-193 [PMID: 12457239 DOI: 10.1007/ s00424-002-0925-7]
43. Ohlsson B, Truedsson M, Bengtsson M, Torstenson R, Sjölund K, Björnsson ES, Simrèn M. Effects of long-term treatment with oxytocin in chronic constipation; a double blind, placebo-controlled pilot trial. Neurogastroenterol Motil 2005; 17: 697-704 [PMID: 16185308 DOI: 10.1111/ j.1365-2982.2005.00679.x]
44. Feng M, Qin J, Wang C, Ye Y, Wang S, Xie D, Wang PS, Liu C. Estradiol upregulates the expression of oxytocin receptor in colon in rats. Am J Physiol Endocrinol Metab 2009; 296: E1059-E1066 [PMID: 19258489 DOI: 10.1152/ajpendo. 90609.2008]
45. Gill RC, Bowes KL, Kingma YJ. Effect of progesterone on canine colonic smooth muscle. Gastroenterology 1985; 88: 1941-1947 [PMID: 3996847]
46. Oh ST, Yedidag E, Bielefeldt K. Differential effects of progesterone and its analogues on the contractility of the murine jejunum in vitro. J Surg Res 1998; 75: 1-5 [PMID: 9614849 DOI: 10.1006/jsre.1997.5152]
47. Liu CY, Chen LB, Liu PY, Xie DP, Wang PS. Effects of progesterone on gastric emptying and intestinal transit in male rats. World J Gastroenterol 2002; 8: 338-341 [PMID: 11925620]
48. Xiao ZL, Pricolo V, Biancani P, Behar J. Role of progesterone signaling in the regulation of G-protein levels in female chronic constipation. Gastroenterology 2005; 128: 667-675 [PMID: 15765402 DOI: 10.1053/j.gastro.2004.12.001]
49. Li CP, Ling C, Biancani P, Behar J. Effect of progesterone on colonic motility and fecal output in mice with diarrhea. Neurogastroenterol Motil 2012; 24: 392-e174 [PMID: 22284724 DOI: 10.1111/j.1365-2982.2011.01875.x]
50. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 2007; 132: 397-414 [PMID: 17241888 DOI: 10.1053/j.gastro.2006.11.002]
51. Pecins-Thompson M, Brown NA, Bethea CL. Regulation of serotonin re-uptake transporter mRNA expression by ovarian steroids in rhesus macaques. Brain Res Mol Brain Res 1998; 53: 120-129 [PMID: 9473622]
52. Gundlah C, Lu NZ, Bethea CL. Ovarian steroid regulation of monoamine oxidase-A and-B mRNAs in the macaque dorsal raphe and hypothalamic nuclei. Psychopharmacology (Berl) 2002; 160: 271-282 [PMID: 11889496 DOI: 10.1007/ s00213-001-0959-0]
53. Smith LJ, Henderson JA, Abell CW, Bethea CL. Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques. Neuropsychopharmacology 2004; 29: 2035-2045 [PMID: 15199371 DOI: 10.1038/sj.npp.1300510]
54. Cheng L, Pricolo V, Biancani P, Behar J. Overexpression of progesterone receptor B increases sensitivity of human colon muscle cells to progesterone. Am J Physiol Gastrointest Liver Physiol 2008; 295: G493-G502 [PMID: 18776045 DOI: 10.1152/ajpgi.90214.2008]
55. Guarino M, Cheng L, Cicala M, Ripetti V, Biancani P, Behar J. Progesterone receptors and serotonin levels in colon epithelial cells from females with slow transit constipation. Neurogastroenterol Motil 2011; 23: 575-e210 [PMID: 21481100 DOI: 10.1111/j.1365-2982.2011.01705.x]
56. Adeyemo MA, Spiegel BM, Chang L. Meta-analysis: do irritable bowel syndrome symptoms vary between men and women? Aliment Pharmacol Ther 2010; 32: 738-755 [PMID: 20662786 DOI: 10.1111/j.1365-2036.2010.04409.x]
57. Herman J, Pokkunuri V, Braham L, Pimentel M. Gender distribution in irritable bowel syndrome is proportional to the severity of constipation relative to diarrhea. Gend Med 2010; 7: 240-246 [PMID: 20638629 DOI: 10.1016/j.genm.2010.06.007]
58. Bearcroft CP, Perrett D, Farthing MJ. Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study. Gut 1998; 42: 42-46 [PMID: 9505884 DOI: 10.1136/gut.42.1.42]
59. Houghton LA, Atkinson W, Whitaker RP, Whorwell PJ, Rimmer MJ. Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome. Gut 2003; 52: 663-670 [PMID: 12692050 DOI: 10.1136/gut.52.5.663]
60. Atkinson W, Lockhart S, Whorwell PJ, Keevil B, Houghton LA. Altered 5-hydroxytryptamine signaling in patients with constipation-and diarrhea-predominant irritable bowel syndrome. Gastroenterology 2006; 130: 34-43 [PMID: 16401466 DOI: 10.1053/j.gastro.2005.09.031]
61. Dunlop SP, Coleman NS, Blackshaw E, Perkins AC, Singh G, Marsden CA, Spiller RC. Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol 2005; 3: 349-357 [PMID: 15822040 DOI: 10.1016/S1542-3565(04)00726-8]
62. Spiller R, Aziz Q, Creed F, Emmanuel A, Houghton L, Hungin P, Jones R, Kumar D, Rubin G, Trudgill N, Whorwell P. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007; 56: 1770-1798 [PMID: 17488783 DOI: 10.1136/gut.2007.119446]
63. Houghton LA, Brown H, Atkinson W, Morris J, Fell C, Whorwell PJ, Lockhart S, Keevil B. 5-hydroxytryptamine signalling in irritable bowel syndrome with diarrhoea: effects of gender and menstrual status. Aliment Pharmacol Ther 2009; 30: 919-929 [PMID: 19691669 DOI: 10.1111/j.1365-2036.2009.04121.x]
64. Fillingim RB, Ness TJ. Sex-related hormonal influences on pain and analgesic responses. Neurosci Biobehav Rev 2000; 24: 485-501 [PMID: 10817845 DOI: 10.1016/ S0149-7634(00)00017-8]
65. Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain 2009; 10: 447-485 [PMID: 19411059 DOI: 10.1016/j.jpain.2008.12.001]
66. Ragnarsson G, Hallböök O, Bodemar G. Abdominal symptoms are not related to anorectal function in the irritable bowel syndrome. Scand J Gastroenterol 1999; 34: 250-258 [PMID: 10232868]
67. Chang L, Mayer EA, Labus JS, Schmulson M, Lee OY, Olivas TI, Stains J, Naliboff BD. Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome. Am J Physiol Regul Integr Comp Physiol 2006; 291: R277-R284 [PMID: 16574882 DOI: 10.1152/ajpregu.00729.2005]
68. Holdcroft A, Sapsed-Byrne S, Ma D, Hammal D, Forsling ML. Sex and oestrous cycle differences in visceromotor responses and vasopressin release in response to colonic distension in male and female rats anaesthetized with halothane. Br J Anaesth 2000; 85: 907-910 [PMID: 11732530]
69. Kamp EH, Jones RC, Tillman SR, Gebhart GF. Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice. Am J Physiol Gastrointest Liver Physiol 2003; 284: G434-G444 [PMID: 12444012 DOI: 10.1152/ajpgi. 00324.2002]
70. Ji Y, Murphy AZ, Traub RJ. Sex differences in morphineinduced analgesia of visceral pain are supraspinally and peripherally mediated. Am J Physiol Regul Integr Comp Physiol 2006; 291: R307-R314 [PMID: 16556902 DOI: 10.1152/ajpregu. 00824.2005]
71. Ji Y, Tang B, Cao DY, Wang G, Traub RJ. Sex differences in spinal processing of transient and inflammatory colorectal stimuli in the rat. Pain 2012; 153: 1965-1973 [PMID: 22819535 DOI: 10.1016/j.pain.2012.06.019]
72. Chaloner A, Greenwood-Van Meerveld B. Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model. J Pain 2013; 14: 270-280 [PMID: 23348370 DOI: 10.1016/j.jpain.2012.11.008]
73. Giamberardino MA, Affaitati G, Valente R, Iezzi S, Vecchiet L. Changes in visceral pain reactivity as a function of estrous cycle in female rats with artificial ureteral calculosis. Brain Res 1997; 774: 234-238 [PMID: 9452216 DOI: 10.1016/ S0006-8993(97)81711-8]
74. Bradshaw HB, Temple JL, Wood E, Berkley KJ. Estrous variations in behavioral responses to vaginal and uterine distention in the rat. Pain 1999; 82: 187-197 [PMID: 10467923 DOI: 10.1016/S0304-3959(99)00049-4]
75. Bradesi S, Eutamene H, Garcia-Villar R, Fioramonti J, Bueno L. Stress-induced visceral hypersensitivity in female rats is estrogen-dependent and involves tachykinin NK1 receptors. Pain 2003; 102: 227-234 [PMID: 12670663]
76. Ji Y, Murphy AZ, Traub RJ. Estrogen modulates the visceromotor reflex and responses of spinal dorsal horn neurons to colorectal stimulation in the rat. J Neurosci 2003; 23: 3908-3915 [PMID: 12736360]
77. Sanoja R, Cervero F. Estrogen-dependent abdominal hyperalgesia induced by ovariectomy in adult mice: a model of functional abdominal pain. Pain 2005; 118: 243-253 [PMID: 16202534 DOI: 10.1016/j.pain.2005.08.021]
78. Lu CL, Hsieh JC, Tsaur ML, Huang YH, Wang PS, Wu LL, Liu PY, Chang FY, Lee SD. Estrogen rapidly modulates mustard oil-induced visceral hypersensitivity in conscious female rats: A role of CREB phosphorylation in spinal dorsal horn neurons. Am J Physiol Gastrointest Liver Physiol 2007; 292: G438-G446 [PMID: 16973918 DOI: 10.1152/ajpgi. 00210.2006]
79. Fan J, Yu LH, Zhang Y, Ni X, Ma B, Burnstock G. Estrogen altered visceromotor reflex and P2X(3) mRNA expression in a rat model of colitis. Steroids 2009; 74: 956-962 [PMID: 19628002 DOI: 10.1016/j.steroids.2009.07.002]
80. Myers B, Schulkin J, Greenwood-Van Meerveld B. Sex steroids localized to the amygdala increase pain responses to visceral stimulation in rats. J Pain 2011; 12: 486-494 [PMID: 21167789 DOI: 10.1016/j.jpain.2010.10.007]
81. Ji Y, Tang B, Traub RJ. The visceromotor response to colorectal distention fluctuates with the estrous cycle in rats. Neuroscience 2008; 154: 1562-1567 [PMID: 18550290 DOI: 10.1016/j.neuroscience.2008.04.070]
82. Peng HY, Huang PC, Liao JM, Tung KC, Lee SD, Cheng CL, Shyu JC, Lai CY, Chen GD, Lin TB. Estrous cycle variation of TRPV1-mediated cross-organ sensitization between uterus and NMDA-dependent pelvic-urethra reflex activity. Am J Physiol Endocrinol Metab 2008; 295: E559-E568 [PMID: 18577691 DOI: 10.1152/ajpendo.90289.2008]
83. Ji Y, Tang B, Traub RJ. Modulatory effects of estrogen and progesterone on colorectal hyperalgesia in the rat. Pain 2005; 117: 433-442 [PMID: 16154701 DOI: 10.1016/j.pain.2005.07.011]
84. Tang B, Ji Y, Traub RJ. Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat. Pain 2008; 137: 540-549 [PMID: 18068901 DOI: 10.1016/j.pain.2007.10.017]
85. Robbins MT, Mebane H, Ball CL, Shaffer AD, Ness TJ. Effect of estrogen on bladder nociception in rats. J Urol 2010; 183: 1201-1205 [PMID: 20096872 DOI: 10.1016/j.juro.2009.11.003]
86. Peng HY, Chen GD, Lai CY, Hsieh MC, Hsu HH, Wu HC, Lin TB. PI3K modulates estrogen-dependent facilitation of colon-to-urethra cross-organ reflex sensitization in ovariectomized female rats. J Neurochem 2010; 113: 54-66 [DOI: 10.1111/j.1471-4159.2010.06577.x]
87. Ji Y, Tang B, Traub RJ. Spinal estrogen receptor alpha mediates estradiol-induced pronociception in a visceral pain model in the rat. Pain 2011; 152: 1182-1191 [PMID: 21392887 DOI: 10.1016/j.pain.2011.01.046]
88. Aloisi AM, Affaitati G, Ceccarelli I, Fiorenzani P, Lerza R, Rossi C, Pace MC, Chiefari M, Aurilio C, Giamberardino MA. Estradiol and testosterone differently affect visceral pain-related behavioural responses in male and female rats. Eur J Pain 2010; 14: 602-607 [PMID: 19948419 DOI: 10.1016/ j.ejpain.2009.10.016]
89. Papka RE, Storey-Workley M. Estrogen receptor-alpha and-beta coexist in a subpopulation of sensory neurons of female rat dorsal root ganglia. Neurosci Lett 2002; 319: 71-74 [PMID: 11825673 DOI: 10.1016/S0304-3940(01)02562-9]
90. Lee DY, Chai YG, Lee EB, Kim KW, Nah SY, Oh TH, Rhim H. 17Beta-estradiol inhibits high-voltage-activated calcium channel currents in rat sensory neurons via a non-genomic mechanism. Life Sci 2002; 70: 2047-2059 [PMID: 12148697]
91. Cho T, Chaban VV. Expression of P2X3 and TRPV1 receptors in primary sensory neurons from estrogen receptors-α and estrogen receptor-β knockout mice. Neuroreport 2012; 23: 530-534 [PMID: 22581043 DOI: 10.1097/WNR.0b013e328353fabc]
92. Chaban VV, Mayer EA, Ennes HS, Micevych PE. Estradiol inhibits atp-induced intracellular calcium concentration increase in dorsal root ganglia neurons. Neuroscience 2003; 118: 941-948 [PMID: 12732239 DOI: 10.1016/ S0306-4522(02)00915-6]
93. Chaban VV, Micevych PE. Estrogen receptor-alpha mediates estradiol attenuation of ATP-induced Ca2+ signaling in mouse dorsal root ganglion neurons. J Neurosci Res 2005; 81: 31-37 [PMID: 15952176 DOI: 10.1002/jnr.20524]
94. Lu CL, Hsieh JC, Dun NJ, Oprea TI, Wang PS, Luo JC, Lin HC, Chang FY, Lee SD. Estrogen rapidly modulates 5-hydroxytrytophan-induced visceral hypersensitivity via GPR30 in rats. Gastroenterology 2009; 137: 1040-1050 [PMID: 19344720 DOI: 10.1053/j.gastro.2009.03.047]
95. Cao DY, Ji Y, Tang B, Traub RJ. Estrogen receptor β activation is antinociceptive in a model of visceral pain in the rat. J Pain 2012; 13: 685-694 [PMID: 22698981 DOI: 10.1016/ j.jpain.2012.04.010]
96. McRoberts JA, Li J, Ennes HS, Mayer EA. Sex-dependent differences in the activity and modulation of N-methyl-daspartic acid receptors in rat dorsal root ganglia neurons. Neuroscience 2007; 148: 1015-1020 [PMID: 17693030 DOI: 10.1016/j.neuroscience.2007.07.006]
97. Chieng BC, Christie MJ, Osborne PB. Characterization of neurons in the rat central nucleus of the amygdala: cellular physiology, morphology, and opioid sensitivity. J Comp Neurol 2006; 497: 910-927 [PMID: 16802333 DOI: 10.1002/ cne.21025]
98. Jaferi A, Pickel VM. Mu-opioid and corticotropin-releasingfactor receptors show largely postsynaptic co-expression, and separate presynaptic distributions, in the mouse central amygdala and bed nucleus of the stria terminalis. Neuroscience 2009; 159: 526-539 [PMID: 19166913 DOI: 10.1016/j.neur oscience.2008.12.061]
99. Beckerman MA, Glass MJ. The NMDA-NR1 receptor subunit and the mu-opioid receptor are expressed in somatodendritic compartments of central nucleus of the amygdala neurons projecting to the bed nucleus of the stria terminalis. Exp Neurol 2012; 234: 112-126 [PMID: 22227057 DOI: 10.1016/j.expneurol.2011.12.034]
100. Sandner-Kiesling A, Eisenach JC. Estrogen reduces efficacy of mu-but Not kappa-opioid agonist inhibition in response to uterine cervical distension. Anesthesiology 2002; 96: 375-379 [PMID: 11818771]
101. Tang YR, Yang WW, Wang YL, Lin L. Sex differences in the symptoms and psychological factors that influence quality of life in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol 2012; 24: 702-707 [PMID: 22382707 DOI: 10.1097/MEG.0b013e328351b2c2]
102. Whitehead WE, Cheskin LJ, Heller BR, Robinson JC, Crowell MD, Benjamin C, Schuster MM. Evidence for exacerbation of irritable bowel syndrome during menses. Gastroenterology 1990; 98: 1485-1489 [PMID: 2338190]
103. Kane SV, Sable K, Hanauer SB. The menstrual cycle and its effect on inflammatory bowel disease and irritable bowel syndrome: a prevalence study. Am J Gastroenterol 1998; 93: 1867-1872 [PMID: 9772046 DOI: 10.1111/j.1572-0241.1998.540_i. x]
104. Olafsdottir LB, Gudjonsson H, Jonsdottir HH, Björnsson E, Thjodleifsson B. Natural History of Irritable Bowel Syndrome in Women and Dysmenorrhea: A 10-Year Follow-Up Study. Gastroenterol Res Pract 2012; 2012: 534204 [DOI: 10.1155/2012/534204]
105. Palsson OS, Whitehead WE, Barghout V, Levy R, Feld A, Von Korff M, Garner M, Drossman DA, Turner MJ. IBS severity and health-related quality of life improve with age in women but not in men. Am J Gastroenterol 2003; 98: S272 [DOI: 10.1016/S0002-9270(03)01590-9]
106. Houghton LA, Jackson NA, Whorwell PJ, Morris J. Do male sex hormones protect from irritable bowel syndrome? Am J Gastroenterol 2000; 95: 2296-2300 [PMID: 11007231 DOI: 10.1111/j.1572-0241.2000.02314.x]
107. Camilleri M, Mayer EA, Drossman DA, Heath A, Dukes GE, McSorley D, Kong S, Mangel AW, Northcutt AR. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 1999; 13: 1149-1159 [PMID: 10468696]
108. Berman SM, Naliboff BD, Chang L, Fitzgerald L, Antolin T, Camplone A, Mayer EA. Enhanced preattentive central nervous system reactivity in irritable bowel syndrome. Am J Gastroenterol 2002; 97: 2791-2797 [PMID: 12425550 DOI: 10.1111/j.1572-0241.2002.07024.x]
109. Kilpatrick LA, Ornitz E, Ibrahimovic H, Treanor M, Craske M, Nazarian M, Labus JS, Mayer EA, Naliboff BD. Sex-related differences in prepulse inhibition of startle in irritable bowel syndrome (IBS). Biol Psychol 2010; 84: 272-278 [PMID: 20193731 DOI: 10.1016/j.biopsycho.2010.02.012]
110. Berkley KJ. Sex differences in pain. Behav Brain Sci 1997; 20: 371-80; discussion 435-513 [PMID: 10097000]
111. Fillingim RB, Maixner W, Kincaid S, Silva S. Sex differences in temporal summation but not sensory-discriminative processing of thermal pain. Pain 1998; 75: 121-127 [PMID: 9539681]
112. Papka RE, Mowa CN. Estrogen receptors in the spinal cord, sensory ganglia, and pelvic autonomic ganglia. Int Rev Cytol 2003; 231: 91-127 [PMID: 14713004]
113. Berman S, Munakata J, Naliboff BD, Chang L, Mandelkern M, Silverman D, Kovalik E, Mayer EA. Gender differences in regional brain response to visceral pressure in IBS patients. Eur J Pain 2000; 4: 157-172 [PMID: 10957697 DOI: 10.1053/eujp.2000.0167]
114. Naliboff BD, Berman S, Chang L, Derbyshire SW, Suyenobu B, Vogt BA, Mandelkern M, Mayer EA. Sex-related differences in IBS patients: central processing of visceral stimuli. Gastroenterology 2003; 124: 1738-1747 [PMID: 12806606 DOI: 10.1016/S0016-5085(03)00400-1]
115. Wilder-Smith CH, Schindler D, Lovblad K, Redmond SM, Nirkko A. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut 2004; 53: 1595-1601 [PMID: 15479679 DOI: 10.1136/gut.2003.028514]
116. Berman SM, Naliboff BD, Suyenobu B, Labus JS, Stains J, Bueller JA, Ruby K, Mayer EA. Sex differences in regional brain response to aversive pelvic visceral stimuli. Am J Physiol Regul Integr Comp Physiol 2006; 291: R268-R276 [PMID: 16614061 DOI: 10.1152/ajpregu.00065.2006]
117. Labus JS, Naliboff BN, Fallon J, Berman SM, Suyenobu B, Bueller JA, Mandelkern M, Mayer EA. Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: a network analysis. Neuroimage 2008; 41: 1032-1043 [PMID: 18450481 DOI: 10.1016/j.neuroimage.2008.03.009]
118. Tillisch K, Mayer EA, Labus JS. Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology 2011; 140: 91-100 [PMID: 20696168 DOI: 10.1053/j.gastro.2010.07.053]
119. Wang Z, Bradesi S, Maarek JM, Lee K, Winchester WJ, Mayer EA, Holschneider DP. Regional brain activation in conscious, nonrestrained rats in response to noxious visceral stimulation. Pain 2008; 138: 233-243 [PMID: 18538929 DOI: 10.1016/j.pain.2008.04.018]
120. Wang Z, Guo Y, Bradesi S, Labus JS, Maarek JM, Lee K, Winchester WJ, Mayer EA, Holschneider DP. Sex differences in functional brain activation during noxious visceral stimulation in rats. Pain 2009; 145: 120-128 [PMID: 19560270 DOI: 10.1016/j.pain.2009.05.025]
121. Hong JY, Kilpatrick LA, Labus J, Gupta A, Jiang Z, Ashe-McNalley C, Stains J, Heendeniya N, Ebrat B, Smith S, Tillisch K, Naliboff B, Mayer EA. Patients with chronic visceral pain show sex-related alterations in intrinsic oscillations of the resting brain. J Neurosci 2013; 33: 11994-12002 [PMID: 23864686 DOI: 10.1523/JNEUROSCI.5733-12.2013]
122. Labus JS, Gupta A, Coveleskie K, Tillisch K, Kilpatrick L, Jarcho J, Feier N, Bueller J, Stains J, Smith S, Suyenobu B, Naliboff B, Mayer EA. Sex differences in emotion-related cognitive processes in irritable bowel syndrome and healthy control subjects. Pain 2013; 154: 2088-2099 [PMID: 23791896 DOI: 10.1016/j.pain.2013.06.024]
123. Blankstein U, Chen J, Diamant NE, Davis KD. Altered brain structure in irritable bowel syndrome: potential contributions of pre-existing and disease-driven factors. Gastroenterology 2010; 138: 1783-1789 [PMID: 20045701 DOI: 10.1053/ j.gastro.2009.12.043]
124. Seminowicz DA, Labus JS, Bueller JA, Tillisch K, Naliboff BD, Bushnell MC, Mayer EA. Regional gray matter density changes in brains of patients with irritable bowel syndrome. Gastroenterology 2010; 139: 48-57. e2 [PMID: 20347816 DOI: 10.1053/j.gastro.2010.03.049]
125. Jiang Z, Dinov ID, Labus J, Shi Y, Zamanyan A, Gupta A, Ashe-McNalley C, Hong JY, Tillisch K, Toga AW, Mayer EA. Sex-related differences of cortical thickness in patients with chronic abdominal pain. PLoS One 2013; 8: e73932 [PMID: 24040118 DOI: 10.1371/journal.pone.0073932]
126. Ellingson BM, Mayer E, Harris RJ, Ashe-McNally C, Naliboff BD, Labus JS, Tillisch K. Diffusion tensor imaging detects microstructural reorganization in the brain associated with chronic irritable bowel syndrome. Pain 2013; 154: 1528-1541 [PMID: 23721972 DOI: 10.1016/j.pain.2013.04.010]
127. Labus JS, Dinov ID, Jiang Z, Ashe-McNalley C, Zamanyan A, Shi Y, Hong JY, Gupta A, Tillisch K, Ebrat B, Hobel S, Gutman BA, Joshi S, Thompson PM, Toga AW, Mayer EA. Irritable bowel syndrome in female patients is associated with alterations in structural brain networks. Pain 2014; 155: 137-149 [PMID: 24076048 DOI: 10.1016/j.pain.2013.09.020]
128. Fukudo S, Kanazawa M, Mizuno T, Hamaguchi T, Kano M, Watanabe S, Sagami Y, Shoji T, Endo Y, Hongo M, Itoyama Y, Yanai K, Tashiro M, Aoki M. Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention. Neuroimage 2009; 47: 946-951 [PMID: 19426812 DOI: 10.1016/j.neuroimage.2009.04.083]
129. Kilpatrick LA, Labus JS, Coveleskie K, Hammer C, Rappold G, Tillisch K, Bueller JA, Suyenobu B, Jarcho JM, McRoberts JA, Niesler B, Mayer EA. The HTR3A polymorphism c.-42C>T is associated with amygdala responsiveness in patients with irritable bowel syndrome. Gastroenterology 2011; 140: 1943-1951 [PMID: 21420406 DOI: 10.1053/j.gastro.2011.03.011]
130. Aloisi AM, Bonifazi M. Sex hormones, central nervous system and pain. Horm Behav 2006; 50: 1-7 [PMID: 16423353 DOI: 10.1016/j.yhbeh.2005.12.002]
131. Cooke BM, Woolley CS. Gonadal hormone modulation of dendrites in the mammalian CNS. J Neurobiol 2005; 64: 34-46 [PMID: 15884004 DOI: 10.1002/neu.20143]
132. Mukai H, Kimoto T, Hojo Y, Kawato S, Murakami G, Higo S, Hatanaka Y, Ogiue-Ikeda M. Modulation of synaptic plasticity by brain estrogen in the hippocampus. Biochim Biophys Acta 2010; 1800: 1030-1044 [PMID: 19909788 DOI: 10.1016/ j.bbagen.2009.11.002]
133. Kramár EA, Babayan AH, Gall CM, Lynch G. Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton. Neuroscience 2013; 239: 3-16 [PMID: 23103216 DOI: 10.1016/j.neuroscience.2012.10.038]
134. Seeman MV. Psychopathology in women and men: focus on female hormones. Am J Psychiatry 1997; 154: 1641-1647 [PMID: 9396940]
135. Young E, Korszun A. Sex, trauma, stress hormones and depression. Mol Psychiatry 2010; 15: 23-28 [PMID: 19773810 DOI: 10.1038/mp.2009.94]
136. Altemus M. Sex differences in depression and anxiety disorders: potential biological determinants. Horm Behav 2006; 50: 534-538 [PMID: 16920114 DOI: 10.1016/j.yhbeh.2006.06.031]
137. Bradford K, Shih W, Videlock EJ, Presson AP, Naliboff BD, Mayer EA, Chang L. Association between early adverse life events and irritable bowel syndrome. Clin Gastroenterol Hepatol 2012; 10: 385-90. e1-3 [PMID: 22178460 DOI: 10.1016/ j.cgh.2011.12.018]
138. Bennett E, Tennant C, Piesse C, Badcock C, Kellow J. Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut 1998; 43: 256
139. Mayer EA, Naliboff BD, Chang L, Coutinho SV. V. Stress and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2001; 280: G519-G524 [PMID: 11254476]
140. Spence MJ, Moss-Morris R. The cognitive behavioural model of irritable bowel syndrome: a prospective investigation of patients with gastroenteritis. Gut 2007; 56: 1066-1071 [PMID: 17324974 DOI: 10.1136/gut.2006.108811]
141. Myers B, Greenwood-Van Meerveld B. Role of anxiety in the pathophysiology of irritable bowel syndrome: importance of the amygdala. Front Neurosci 2009; 3: 47 [PMID: 20582274 DOI: 10.3389/neuro.21.002.2009]
142. Chaloner A, Greenwood-Van Meerveld B. Early life adversity as a risk factor for visceral pain in later life: importance of sex differences. Front Neurosci 2013; 7: 13 [PMID: 23407595 DOI: 10.3389/fnins.2013.00013]
143. Tillisch K, Mayer EA, Labus JS, Stains J, Chang L, Naliboff BD. Sex specific alterations in autonomic function among patients with irritable bowel syndrome. Gut 2005; 54: 1396-1401 [PMID: 15923667 DOI: 10.1136/gut.2004.058685]
144. Kudielka BM, Kirschbaum C. Sex differences in HPA axis responses to stress: a review. Biol Psychol 2005; 69: 113-132 [PMID: 15740829 DOI: 10.1016/j.biopsycho.2004.11.009]
145. Videlock EJ, Adeyemo M, Licudine A, Hirano M, Ohning G, Mayer M, Mayer EA, Chang L. Childhood trauma is associated with hypothalamic-pituitary-adrenal axis responsiveness in irritable bowel syndrome. Gastroenterology 2009; 137: 1954-1962 [PMID: 19737564 DOI: 10.1053/ j.gastro.2009.08.058]
146. Young EA. Sex differences in response to exogenous corticosterone: a rat model of hypercortisolemia. Mol Psychiatry 1996; 1: 313-319 [PMID: 9118357]
147. Smith RF, Ghuman SP, Evans NP, Karsch FJ, Dobson H. Stress and the control of LH secretion in the ewe. Reprod Suppl 2003; 61: 267-282 [PMID: 14635941]
148. Ochedalski T, Subburaju S, Wynn PC, Aguilera G. Interaction between oestrogen and oxytocin on hypothalamic-pituitary-adrenal axis activity. J Neuroendocrinol 2007; 19: 189-197 [PMID: 17280592 DOI: 10.1111/j.1365-2826.2006.01525.x]
149. Logrip ML, Rivier C, Lau C, Im S, Vaughan J, Lee S. Adolescent alcohol exposure alters the rat adult hypothalamicpituitary-adrenal axis responsiveness in a sex-specific manner. Neuroscience 2013; 235: 174-186 [PMID: 23337533 DOI: 10.1016/j.neuroscience.2012.12.069]
150. Handa RJ, Burgess LH, Kerr JE, O'Keefe JA. Gonadal steroid hormone receptors and sex differences in the hypothalamopituitary-adrenal axis. Horm Behav 1994; 28: 464-476 [PMID: 7729815 DOI: 10.1006/hbeh.1994.1044]
151. Nappi RE, Rivest S. Ovulatory cycle influences the stimulatory effect of stress on the expression of corticotropinreleasing factor receptor messenger ribonucleic acid in the paraventricular nucleus of the female rat hypothalamus. Endocrinology 1995; 136: 4073-4083 [PMID: 7649116]
152. Nappi RE, Rivest S. Stress-induced genetic expression of a selective corticotropin-releasing factor-receptor subtype within the rat ovaries: an effect dependent on the ovulatory cycle. Biol Reprod 1995; 53: 1417-1428 [PMID: 8562699 DOI: 10.1095/biolreprod53.6.1417]
153. Suárez-Hitz KA, Otto B, Bidlingmaier M, Schwizer W, Fried M, Ehlert U. Altered psychobiological responsiveness in women with irritable bowel syndrome. Psychosom Med 2012; 74: 221-231 [PMID: 22286854 DOI: 10.1097/ PSY.0b013e318244fb82]
154. Elsenbruch S, Lovallo WR, Orr WC. Psychological and physiological responses to postprandial mental stress in women with the irritable bowel syndrome. Psychosom Med 2001; 63: 805-813 [PMID: 11573029]
155. Salmon P, Skaife K, Rhodes J. Abuse, dissociation, and somatization in irritable bowel syndrome: towards an explanatory model. J Behav Med 2003; 26: 1-18 [PMID: 12690943]
156. Creed F, Tomenson B, Guthrie E, Ratcliffe J, Fernandes L, Read N, Palmer S, Thompson DG. The relationship between somatisation and outcome in patients with severe irritable bowel syndrome. J Psychosom Res 2008; 64: 613-620 [PMID: 18501262 DOI: 10.1016/j.jpsychores.2008.02.016]
157. Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Meaney MJ, Plotsky PM. Long-term behavioral and neuroendocrine adaptations to adverse early experience. Prog Brain Res 2000; 122: 81-103 [PMID: 10737052]
158. Li TJ, Yu BP, Dong WG, Luo HS, Xu L, Li MQ. Ovarian hormone modulates 5-hydroxytryptamine 3 receptors mRNA expression in rat colon with restraint stress-induced bowel dysfunction. World J Gastroenterol 2004; 10: 2723-2726 [PMID: 15309727]
159. Bradesi S, Eutamene H, Fioramonti J, Bueno L. Acute restraint stress activates functional NK1 receptor in the colon of female rats: involvement of steroids. Gut 2002; 50: 349-354 [PMID: 11839713 DOI: 10.1136/gut.50.3.349]
160. Bond EF, Heitkemper MM, Bailey SL. Estrogen suppresses gastric motility response to thyrotropin-releasing hormone and stress in awake rats. Res Nurs Health 1998; 21: 221-228 [PMID: 9609507 DOI: 10.1002/(SICI)1098-240X(199806)21:3<221::AID-NUR5>3.0.CO;2-J]
161. Taché Y, Martinez V, Wang L, Million M. CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome. Br J Pharmacol 2004; 141: 1321-1330 [PMID: 15100165 DOI: 10.1038/sj.bjp.0705760]
162. Taché Y, Million M, Nelson AG, Lamy C, Wang L. Role of corticotropin-releasing factor pathways in stress-related alterations of colonic motor function and viscerosensibility in female rodents. Gend Med 2005; 2: 146-154 [PMID: 16290887 DOI: 10.1016/S1550-8579(05)80043-9]
163. Larauche M, Mulak A, Kim YS, Labus J, Million M, Taché Y. Visceral analgesia induced by acute and repeated water avoidance stress in rats: sex difference in opioid involvement. Neurogastroenterol Motil 2012; 24: 1031-e547 [PMID: 22776034 DOI: 10.1111/j.1365-2982.2012.01980.x]
164. Alonso C, Guilarte M, Vicario M, Ramos L, Ramadan Z, Antolín M, Martínez C, Rezzi S, Saperas E, Kochhar S, Santos J, Malagelada JR. Maladaptive intestinal epithelial responses to life stress may predispose healthy women to gut mucosal inflammation. Gastroenterology 2008; 135: 163-172. e1 [PMID: 18455999 DOI: 10.1053/j.gastro.2008.03.036]
165. Alonso C, Guilarte M, Vicario M, Ramos L, Rezzi S, Martínez C, Lobo B, Martin FP, Pigrau M, González-Castro AM, Gallart M, Malagelada JR, Azpiroz F, Kochhar S, Santos J. Acute experimental stress evokes a differential gender-determined increase in human intestinal macromolecular permeability. Neurogastroenterol Motil 2012; 24: 740-76, e348-9 [PMID: 22625665 DOI: 10.1111/j.1365-2982.2012.01928.x]
166. Meddings JB, Swain MG. Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat. Gastroenterology 2000; 119: 1019-1028 [PMID: 11040188 DOI: 10.1053/gast.2000.18152]
167. Santos J, Perdue MH. Stress and neuroimmune regulation of gut mucosal function. Gut 2000; 47 Suppl 4: iv49-i51; discussion iv52 [PMID: 11076912 DOI: 10.1136/gut.47.suppl_4. iv49]
168. Söderholm JD, Perdue MH. Stress and gastrointestinal tract. II. Stress and intestinal barrier function. Am J Physiol Gastrointest Liver Physiol 2001; 280: G7-G13 [PMID: 11123192]
169. Ferrier L, Mazelin L, Cenac N, Desreumaux P, Janin A, Emilie D, Colombel JF, Garcia-Villar R, Fioramonti J, Bueno L. Stress-induced disruption of colonic epithelial barrier: role of interferon-gamma and myosin light chain kinase in mice. Gastroenterology 2003; 125: 795-804 [PMID: 12949725 DOI: 10.1016/S0016-5085(03)01057-6]
170. Barreau F, Cartier C, Leveque M, Ferrier L, Moriez R, Laroute V, Rosztoczy A, Fioramonti J, Bueno L. Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay. J Physiol 2007; 580: 347-56 [DOI: 10.1113/jphysiol.2006.120907]
171. Santos J, Yang PC, Söderholm JD, Benjamin M, Perdue MH. Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut 2001; 48: 630-636 [PMID: 11302959 DOI: 10.1136/gut.48.5.630]
172. Demaude J, Salvador-Cartier C, Fioramonti J, Ferrier L, Bueno L. Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction. Gut 2006; 55: 655-661 [PMID: 16299034 DOI: 10.1136/gut.2005.078675]
173. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjöld M, Gustafsson JA. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 1997; 82: 4258-4265 [PMID: 9398750 DOI: 10.1210/jc.82.12.4258]
174. Campbell-Thompson M, Reyher KK, Wilkinson LB. Immunolocalization of estrogen receptor alpha and beta in gastric epithelium and enteric neurons. J Endocrinol 2001; 171: 65-73 [PMID: 11572791 DOI: 10.1677/joe.0.1710065]
175. Konstantinopoulos P, Kominea A, Vandoros G, Sykiotis G., Andricopoulos P, Varakis I, Sotiropoulou-Bonikou G, Papavassiliou A. Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer 2003; 39: 1251-1258 [DOI: 10.1016/ S0959-8049(03)00239-9]
176. Kawano N, Koji T, Hishikawa Y, Murase K, Murata I, Kohno S. Identification and localization of estrogen receptor alpha-and beta-positive cells in adult male and female mouse intestine at various estrogen levels. Histochem Cell Biol 2004; 121: 399-405 [PMID: 15138841 DOI: 10.1007/ s00418-004-0644-6]
177. Wada-Hiraike O, Warner M, Gustafsson JA. New developments in oestrogen signalling in colonic epithelium. Biochem Soc Trans 2006; 34: 1114-1116 [PMID: 17073763 DOI: 10.1042/BST0341114]
178. Enmark E, Gustafsson JA. Oestrogen receptors-an overview. J Intern Med 1999; 246: 133-138 [PMID: 10447781 DOI: 10.1046/j.1365-2796.1999.00545.x]
179. Wada-Hiraike O, Imamov O, Hiraike H, Hultenby K, Schwend T, Omoto Y, Warner M, Gustafsson JA. Role of estrogen receptor beta in colonic epithelium. Proc Natl Acad Sci USA 2006; 103: 2959-2964 [PMID: 16477031 DOI: 10.1073/pnas.0511271103]
180. Condliffe SB, Doolan CM, Harvey BJ. 17beta-oestradiol acutely regulates Cl-secretion in rat distal colonic epithelium. J Physiol 2001; 530: 47-54 [PMID: 11136857 DOI: 10.1111/j.1469-7793.2001.0047m.x]
181. Cotter AA, Cashman KD. Effect of 17beta-oestradiol on transepithelial calcium transport in human intestinal-like Caco-2 cells and its interactions with 1,25-dihydroxycholecalciferol and 9-cis retinoic acid. Eur J Nutr 2006; 45: 234-241 [PMID: 16491319 DOI: 10.1007/s00394-006-0590-2]
182. Pirani T, Chen J, Vieira A. Effects of estradiol on the endocytic transport of vitamin D carrier protein in hepatocytes. Biochim Biophys Acta 2013; 1830: 3421-3426 [PMID: 23416408 DOI: 10.1016/j.bbagen.2013.01.025]
183. Boyko EJ, Theis MK, Vaughan TL, Nicol-Blades B. Increased risk of inflammatory bowel disease associated with oral contraceptive use. Am J Epidemiol 1994; 140: 268-278 [PMID: 8030630]
184. Cornish JA, Tan E, Simillis C, Clark SK, Teare J, Tekkis PP. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am J Gastroenterol 2008; 103: 2394-2400 [PMID: 18684177 DOI: 10.1111/j.1572-0241.2008.02064.x]
185. Kane SV, Reddy D. Hormonal replacement therapy after menopause is protective of disease activity in women with inflammatory bowel disease. Am J Gastroenterol 2008; 103: 1193-1196 [PMID: 18177456 DOI: 10.1111/j.1572-0241.2007.01700.x]
186. Homma H, Hoy E, Xu DZ, Lu Q, Feinman R, Deitch EA. The female intestine is more resistant than the male intestine to gut injury and inflammation when subjected to conditions associated with shock states. Am J Physiol Gastrointest Liver Physiol 2005; 288: G466-G472 [PMID: 15499084 DOI: 10.1152/ajpgi.00036.2004]
187. Braniste V, Leveque M, Buisson-Brenac C, Bueno L, Fioramonti J, Houdeau E. Oestradiol decreases colonic permeability through oestrogen receptor beta-mediated upregulation of occludin and junctional adhesion molecule-A in epithelial cells. J Physiol 2009; 587: 3317-3328 [PMID: 19433574 DOI: 10.1113/jphysiol.2009.169300]
188. Braniste V, Jouault A, Gaultier E, Polizzi A, Buisson-Brenac C, Leveque M, Martin PG, Theodorou V, Fioramonti J, Houdeau E. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats. Proc Natl Acad Sci USA 2010; 107: 448-453 [PMID: 20018722 DOI: 10.1073/pnas.0907697107]
189. Looijer-van Langen M, Hotte N, Dieleman LA, Albert E, Mulder C, Madsen KL. Estrogen receptor-β signaling modulates epithelial barrier function. Am J Physiol Gastrointest Liver Physiol 2011; 300: G621-G626 [PMID: 21252046 DOI: 10.1152/ajpgi.00274.2010]
190. Moussa L, Bézirard V, Salvador-Cartier C, Bacquié V, Houdeau E, Théodorou V. A new soy germ fermented ingredient displays estrogenic and protease inhibitor activities able to prevent irritable bowel syndrome-like symptoms in stressed female rats. Clin Nutr 2013; 32: 51-58 [PMID: 22727545 DOI: 10.1016/j.clnu.2012.05.021]
191. Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain 2009; 146: 41-46 [PMID: 19595511 DOI: 10.1016/ j.pain.2009.06.017]
192. Kerckhoffs AP, Akkermans LM, de Smet MB, Besselink MG, Hietbrink F, Bartelink IH, Busschers WB, Samsom M, Renooij W. Intestinal permeability in irritable bowel syndrome patients: effects of NSAIDs. Dig Dis Sci 2010; 55: 716-723 [PMID: 19255843 DOI: 10.1007/s10620-009-0765-9]
193. Sankaran-Walters S, Macal M, Grishina I, Nagy L, Goulart L, Coolidge K, Li J, Fenton A, Williams T, Miller MK, Flamm J, Prindiville T, George M, Dandekar S. Sex differences matter in the gut: effect on mucosal immune activation and inflammation. Biol Sex Differ 2013; 4: 10 [PMID: 23651648 DOI: 10.1186/2042-6410-4-10]
194. Beeson PB. Age and sex associations of 40 autoimmune diseases. Am J Med 1994; 96: 457-462 [PMID: 8192178 DOI: 10.1016/0002-9343(94)90173-2]
195. Hewagama A, Patel D, Yarlagadda S, Strickland FM, Richardson BC. Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes Immun 2009; 10: 509-516 [PMID: 19279650 DOI: 10.1038/ gene.2009.12]
196. Kovats S. Estrogen receptors regulate an inflammatory pathway of dendritic cell differentiation: mechanisms and implications for immunity. Horm Behav 2012; 62: 254-262 [PMID: 22561458 DOI: 10.1016/j.yhbeh.2012.04.011]
197. Oertelt-Prigione S. The influence of sex and gender on the immune response. Autoimmun Rev 2012; 11: A479-A485 [PMID: 22155201 DOI: 10.1016/j.autrev.2011.11.022]
198. Cutolo M, Sulli A, Straub RH. Estrogen metabolism and autoimmunity. Autoimmun Rev 2012; 11: A460-A464 [PMID: 22155198 DOI: 10.1016/j.autrev.2011.11.014]
199. Stygar D, Westlund P, Eriksson H, Sahlin L. Identification of wild type and variants of oestrogen receptors in polymorphonuclear and mononuclear leucocytes. Clin Endocrinol (Oxf) 2006; 64: 74-81 [PMID: 16402932 DOI: 10.1111/ j.1365-2265.2005.02420.x]
200. Rider V, Li X, Peterson G, Dawson J, Kimler BF, Abdou NI. Differential expression of estrogen receptors in women with systemic lupus erythematosus. J Rheumatol 2006; 33: 1093-1101 [PMID: 16755656]
201. Inui A, Ogasawara H, Naito T, Sekigawa I, Takasaki Y, Hayashida Y, Takamori K, Ogawa H. Estrogen receptor expression by peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Clin Rheumatol 2007; 26: 1675-1678 [PMID: 17874259 DOI: 10.1007/s10067-007-0568-3]
202. Cunningham M, Gilkeson G. Estrogen receptors in immunity and autoimmunity. Clin Rev Allergy Immunol 2011; 40: 66-73 [PMID: 20352526 DOI: 10.1007/s12016-010-8203-5]
203. Bonnelye E, Laurin N, Jurdic P, Hart DA, Aubin JE. Estrogen receptor-related receptor-alpha (ERR-alpha) is dysregulated in inflammatory arthritis. Rheumatology (Oxford) 2008; 47: 1785-1791 [PMID: 18927192 DOI: 10.1093/rheumatology/ ken368]
204. Chen FP, Wang KC, Huang JD. Effect of estrogen on the activity and growth of human osteoclasts in vitro. Taiwan J Obstet Gynecol 2009; 48: 350-355 [PMID: 20045755 DOI: 10.1016/S1028-4559(09)60323-5]
205. Subramanian M, Shaha C. Oestrogen modulates human macrophage apoptosis via differential signalling through oestrogen receptor-alpha and beta. J Cell Mol Med 2009; 13: 2317-2329 [PMID: 20141615 DOI: 10.1111/j.1582-4934.2008.00679.x]
206. Giannoni E, Guignard L, Knaup Reymond M, Perreau M, Roth-Kleiner M, Calandra T, Roger T. Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns. Infect Immun 2011; 79: 2690-2698 [PMID: 21518785 DOI: 10.1128/IAI.00076-11]
207. Egger B, Bajaj-Elliott M, MacDonald TT, Inglin R, Eysselein VE, Büchler MW. Characterisation of acute murine dextran sodium sulphate colitis: cytokine profile and dose dependency. Digestion 2000; 62: 240-248 [PMID: 11070407]
208. Burger D, Dayer JM. Cytokines, acute-phase proteins, and hormones: IL-1 and TNF-alpha production in contact-mediated activation of monocytes by T lymphocytes. Ann N Y Acad Sci 2002; 966: 464-473 [PMID: 12114305 DOI: 10.1111/ j.1749-6632.2002.tb04248.x]
209. Priyanka HP, Krishnan HC, Singh RV, Hima L, Thyagarajan S. Estrogen modulates in vitro T cell responses in a concentration-and receptor-dependent manner: effects on intracellular molecular targets and antioxidant enzymes. Mol Immunol 2013; 56: 328-339 [PMID: 23911387 DOI: 10.1016/ j.molimm.2013.05.226]
210. Vasiadi M, Kempuraj D, Boucher W, Kalogeromitros D, Theoharides TC. Progesterone inhibits mast cell secretion. Int J Immunopathol Pharmacol 2006; 19: 787-794 [PMID: 17166400]
211. Vliagoftis H, Dimitriadou V, Boucher W, Rozniecki JJ, Correia I, Raam S, Theoharides TC. Estradiol augments while tamoxifen inhibits rat mast cell secretion. Int Arch Allergy Immunol 1992; 98: 398-409 [PMID: 1384869]
212. Page ST, Plymate SR, Bremner WJ, Matsumoto AM, Hess DL, Lin DW, Amory JK, Nelson PS, Wu JD. Effect of medical castration on CD4+ CD25+ T cells, CD8+ T cell IFNgamma expression, and NK cells: a physiological role for testosterone and/or its metabolites. Am J Physiol Endocrinol Metab 2006; 290: E856-E863 [PMID: 16352669 DOI: 10.1152/ ajpendo.00484.2005]
213. Cremon C, Gargano L, Morselli-Labate AM, Santini D, Cogliandro RF, De Giorgio R, Stanghellini V, Corinaldesi R, Barbara G. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol 2009; 104: 392-400 [PMID: 19174797 DOI: 10.1038/ajg.2008.94]
214. Theoharides TC, Cochrane DE. Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol 2004; 146: 1-12 [PMID: 14698841 DOI: 10.1016/ j.jneuroim.2003.10.041]
215. Mayer EA, Berman S, Chang L, Naliboff BD. Sex-based differences in gastrointestinal pain. Eur J Pain 2004; 8: 451-463 [PMID: 15324776 DOI: 10.1016/j.ejpain.2004.01.006]