Abstract
Trauma remains the major cause of deaths in the United States and in other developing countries. Moreover, a significant number of trauma victims who survive initial injury succumb subsequently because of sepsis and multiple organ failure (Bone, 1992; Nathens and Marshall, 1996; Baue et al., 1998; Marshall, 1999; Angele et al., 2000; Baue, 2000; Choudhry et al., 2003).Thus, sepsis and organ dysfunction continue to be the major cause of morbidity and mortality in trauma patients. Although intensive investigations during the past three decades have helped identify some of the mechanisms responsible for sepsis and organ dysfunction, despite all these efforts the prognosis of trauma patients remains elusive. Furthermore, these studies suggest that the postinjury pathogenesis is complex and is influenced by multiple factors.Among these, gender is suspected to be a major factor that plays a significant role in shaping the host response to injury (Schroder et al., 1998; Angele et al., 2000; Schroder et al., 2000; Croce et al., 2002; Yokoyama et al., 2002; Chaudry et al., 2003; George et al., 2003b; Choudhry et al., 2004). The primary aim of this article is to present a comprehensive summary of the studies dealing with the role of gender in response to trauma as well as to discuss potential targets that can be used to modulate endogenous levels of sex hormones to improve organ functions after experimental trauma.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Ancey, C., Corbi, P., Froger, J., Delwail, A., Wijdenes, J., Gascan, H., Potreau, D., and Lecron, J.C. (2002). Secretion of IL-6, IL-11 and LIF by human cardiomyocytes in primary culture. Cytokine 18:199–205.
Angele, M.K., Wichmann, M.W., Ayala, A., Cioffi, W.G., and Chaudry, I.H. (1997). Testosterone receptor blockade after hemorrhage in males. Restoration of the depressed immune functions and improved survival following subsequent sepsis. Arch. Surg. 132:1207–1214.
Angele, M.K., Ayala, A., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (1998a). Testosterone: The culprit for producing splenocyte immune depression after trauma hemorrhage. Am. J. Physiol. 274:C1530–C1536.
Angele, M.K., Catania, R.A., Ayala, A., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (1998b). Dehydroepiandrosterone: An inexpensive steroid hormone that decreases the mortality due to sepsis following trauma-induced hemorrhage. Arch. Surg. 133:1281–1288.
Angele, M.K., Smail, N., Wang, P., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (1998c). L-arginine restores the depressed cardiac output and regional perfusion after trauma-hemorrhage. Surgery 124:394–401.
Angele, M.K., Schwacha, M.G., Ayala, A., and Chaudry, I.H. (2000). Effect of gender and sex hormones on immune responses following shock. Shock 14:81–90.
Angele, M.K., Knoferl, M.W., Ayala, A., Bland, K.I., and Chaudry, I.H. (2001). Testosterone and estrogen differently effect Th1 and Th2 cytokine release following trauma-haemorrhage. Cytokine 16:22–30.
Arora, A., and Potter, J.F. (2004). Aromatase inhibitors: current indications and future prospects for treatment of postmenopausal breast cancer. J. Am. Geriatr. Soc. 52:611–616.
Ayala, A., Perrin, M.M., Ertel, W., and Chaudry, I.H. (1992). Differential effects of hemorrhage on Kupffer cells: Decreased antigen presentation despite increased inflammatory cytokine (IL-1, IL-6 and TNF) release. Cytokine 4:66–75.
Ba, Z.F., Wang, P., Koo, D.J., Ornan, D.A., Bland, K.I., and Chaudry, I.H. (2001). Attenuation of vascular endothelial dysfunction by testosterone receptor blockade after trauma and hemorrhagic shock. Arch. Surg. 136:1158–1163.
Ba, Z.F., Kuebler, J.F., Rue, L.W., III, Bland, K.I., Wang, P., and Chaudry, I.H. (2003). Gender dimorphic tissue perfusion response after acute hemorrhage and resuscitation: Role of vascular endothelial cell function. Am. J. Physiol. Heart Circ. Physiol. 284:H2162–H2169.
Baue, A.E. (2000). A debate on the subject “Are SIRS and MODS important entities in the clinical evaluation of patients?” The con position. Shock 14:590–593.
Baue, A.E., Durham, R., and Faist, E. (1998). Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): Are we winning the battle? Shock 10:79–89.
Baulieu, E.E., Thomas, G., Legrain, S., Lahlou, N., Roger, M., Debuire, B., Faucounau, V., Girard, L., Hervy, M.P., Latour, F., Leaud, M.C., Mokrane, A., Pitti-Ferrandi, H., Trivalle, C., de Lacharriere, O., Nouveau, S., Rakoto-Arison, B., Souberbielle, J.C., Raison, J., Le Bouc, Y., Raynaud, A., Girerd, X., and Forette, F. (2000). Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: Contribution of the DHEAge Study to a sociobiomedical issue. Proc. Natl. Acad. Sci. U.S.A. 97:4279–4284.
Benten, W.P., Lieberherr, M., Stamm, O., Wrehlke, C., Guo, Z., and Wunderlich, F. (1999). Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages. Mol. Biol. Cell 10:3113–3123.
Bone, R.C. (1992). Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA 268:3452–3455.
Bowles, B.J., Roth, B., and Demetriades, D. (2003). Sexual dimorphism in trauma? A retrospective evaluation of outcome. Injury 34:27–31.
Brodie, A.M., and Njar, V.C. (2000). Aromatase inhibitors and their application in breast cancer treatment. Steroids 65:171–179.
Brown, G.A., Vukovich, M.D., Sharp, R.L., Reifenrath, T.A., Parsons, K.A., and King, D.S. (1999). Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men. J. Appl. Physiol. 87:2274–2283.
Case, J., and Davison, C.A. (1999). Estrogen alters relative contributions of nitric oxide and cyclooxygenase products to endothelium-dependent vasodilation. J. Pharmacol. Exp. Ther. 291:524–530.
Catania, R.A., Angele, M.K., Ayala, A., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (1999). Dehydroepiandrosterone restores immune function following trauma-haemorrhage by a direct effect on T lymphocytes. Cytokine 11:443–450.
Chaudry, I.H., Ayala, A., Ertel, W., and Stephan, R.N. (1990). Hemorrhage and resuscitation: Immunological aspects. Am. J. Physiol. 259:R663–R678.
Chaudry, I.H., Samy, T.S., Schwacha, M.G., Wang, P., Rue, L.W., III, and Bland, K.I. (2003). Endocrine targets in experimental shock. J. Trauma 54:S118–S125.
Choudhry, M.A., Schwacha, M.G., Matsutani, T., Bland, K.I., and Chaudry, I.H. (2003). Cellular, molecular and sexual dimorphic response to traumahemorrhage. In M. Ogawa, H. Yamamoto, and M. Hirota (eds.), The Biological Response to Planned and Unplanned Injuries: Cellular, Molecular and Genetic Aspects. New York: Elsevier, pp. 25–38.
Choudhry, M.A., Rana, S.N., Kavanaugh, M.J., Kovacs, E.J., Gamelli, R.L., and Sayeed, M.M. (2004). Impaired intestinal immunity and barrier function: A cause for enhanced bacterial translocation in alcohol intoxication and burn injury. Alcohol 33:199–208.
Croce, M.A., Fabian, T.C., Malhotra, A.K., Bee, T.K., and Miller, P.R. (2002). Does gender difference influence outcome? J. Trauma 53:889–894.
Diodato, M.D., Knoferl, M.W., Schwacha, M.G., Bland, K.I., and Chaudry, I.H. (2001). Gender differences in the inflammatory response and survival following haemorrhage and subsequent sepsis. Cytokine 14:162–169.
Eachempati, S.R., Hydo, L., and Barie, P.S. (1999). Gender-based differences in outcome in patients with sepsis. Arch. Surg. 134:1342–1347.
Erlandsson, M.C., Ohlsson, C., Gustafsson, J.A., and Carlsten, H. (2001). Role of oestrogen receptors alpha and beta in immune organ development and in oestrogen-mediated effects on thymus. Immunology 103:17–25.
Eskandari, F., and Sternberg, E.M. (2002). Neural-immune interactions in health and disease. Ann. N.Y.Acad. Sci. 966:20–27.
Eskandari, F., Webster, J.I., and Sternberg, E.M. (2003). Neural immune pathways and their connection to inflammatory diseases. Arthritis Res. Ther. 5:251–265.
Flores, E., Bratoeff, E., Cabeza, M., Ramirez, E., Quiroz, A., and Heuze, I. (2003). Steroid 5alpha-reductase inhibitors. Mini. Rev. Med. Chem. 3:225–237.
Furr, B.J. (1996). The development of Casodex (bicalutamide): Preclinical studies. Eur. Urol. 29(Suppl 2):83–95.
Gannon, C.J., Pasquale, M., Tracy, J.K., McCarter, R.J., and Napolitano, L.M. (2004). Male gender is associated with increased risk for postinjury pneumonia. Shock 21:410–414.
George, R.L., McGwin, G., Jr., Metzger, J., Chaudry, I.H., and Rue, L.W., III (2003a). The association between gender and mortality among trauma patients as modified by age. J. Trauma 54:464–471.
George, R.L., McGwin, G., Jr., Windham, S.T., Melton, S.M., Metzger, J., Chaudry, I.H., and Rue, L.W., III (2003b). Age-related gender differential in outcome after blunt or penetrating trauma. Shock 19:28–32.
Hierholzer, C., Kalff, J.C., Omert, L., Tsukada, K., Loeffert, J.E., Watkins, S.C., Billiar, T.R., and Tweardy, D.J. (1998). Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury. Am. J. Physiol. 275:L611–L621.
Jarrar, D., Wang, P., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000a). Mechanisms of the salutary effects of dehydroepiandrosterone after trauma-hemorrhage: Direct or indirect effects on cardiac and hepatocellular functions? Arch. Surg. 135:416–422.
Jarrar, D., Wang, P., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000b). The female reproductive cycle is an important variable in the response to trauma-hemorrhage. Am. J. Physiol. Heart Circ. Physiol. 279:H1015–H1021.
Jarrar, D., Wang, P., Knoferl, M.W., Kuebler, J.F., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000c). Insight into the mechanism by which estradiol improves organ functions after trauma-hemorrhage. Surgery 128:246–252.
Jarrar, D., Wang, P., Song, G.Y., Knoferl, M.W., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000d). Metoclopramide: A novel adjunct for improving cardiac and hepatocellular functions after trauma-hemorrhage. Am. J. Physiol. Endocrinol. Metab. 278:E90–E95.
Jarrar, D., Kuebler, J.F., Wang, P., Bland, K.I., and Chaudry, I.H. (2001). DHEA: A novel adjunct for the treatment of male trauma patients. Trends Mol. Med. 7:81–85.
Jarrar, D., Kuebler, J.F., Rue, L.W., III, Matalon, S., Wang, P., Bland, K.I., and Chaudry, I.H. (2002). Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on NF-kappaB and MAPK/ERK mechanisms. Am. J. Physiol. Lung Cell Mol. Physiol. 283:L799–L805.
Jarrar, D., Song, G.Y., Kuebler, J.F., Rue, L.W., Bland, K.I., and Chaudry, I.H. (2004). The effect of inhibition of a major cell signaling pathway following trauma hemorrhage on hepatic injury and interleukin 6 levels. Arch. Surg. 139:896–901.
Kahlke, V., Angele, M.K., Ayala, A., Schwacha, M.G., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000a). Immune dysfunction following trauma-haemorrhage: Influence of gender and age. Cytokine 12:69–77.
Kahlke, V., Angele, M.K., Schwacha, M.G., Ayala, A., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000b). Reversal of sexual dimorphism in splenic T lymphocyte responses after trauma-hemorrhage with aging. Am. J. Physiol. Cell Physiol. 278:C509–C516.
Katzenellenbogen, B.S., and Katzenellenbogen, J. A. (2000). Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta: Regulation by selective estrogen receptor modulators and importance in breast cancer. Breast Cancer Res. 2:335–344.
Kerger, H., Waschke, K.F., Ackern, K.V., Tsai, A.G., and Intaglietta, M. (1999). Systemic and microcirculatory effects of autologous whole blood resuscitation in severe hemorrhagic shock. Am. J. Physiol. 276:H2035–H2043.
Kincade, P.W., Medina, K.L., Payne, K.J., Rossi, M.I., Tudor, K.S., Yamashita, Y., and Kouro, T. (2000). Early B-lymphocyte precursors and their regulation by sex steroids. Immunol. Rev. 175:128–137.
Knoferl, M.W., Diodato, M.D., Angele, M.K., Ayala, A., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000). Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage? Arch. Surg. 135:425–433.
Knoferl, M.W., Jarrar, D., Angele, M.K., Ayala, A., Schwacha, M.G., Bland, K.I., and Chaudry, I.H. (2001). 17 beta-Estradiol normalizes immune responses in ovar-iectomized females after trauma-hemorrhage. Am. J. Physiol. Cell Physiol. 281:C1131–C1138.
Knoferl, M.W., Angele, M.K., Schwacha, M.G., Bland, K.I., and Chaudry, I.H. (2002). Preservation of splenic immune functions by female sex hormones after trauma-hemorrhage. Crit. Care Med. 30:888–893.
Kolvenbag, G.J., and Nash, A. (1999). Bicalutamide dosages used in the treatment of prostate cancer. Prostate 39:47–53.
Kos, M., Denger, S., Reid, G., and Gannon, F. (2002). Upstream open reading frames regulate the translation of the multiple mRNA variants of the estrogen receptor alpha. J. Biol. Chem. 277:37131–37138.
Kovacs, E.J., Messingham, K.A., and Gregory, M.S. (2002). Estrogen regulation of immune responses after injury. Mol. Cell Endocrinol. 193:129–135.
Kuebler, J.F., Jarrar, D., Wang, P., Bland, K.I., and Chaudry, I.H. (2001). Dehy-droepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage. J. Surg. Res. 97:196–201.
Kuebler, J.F., Jarrar, D., Toth, B., Bland, K.I., Rue, L., III, Wang, P., and Chaudry, I.H. (2002). Estradiol administration improves splanchnic perfusion following trauma-hemorrhage and sepsis. Arch. Surg. 137:74–79.
Landers, J.P., and Spelsberg, T.C. (1992). New concepts in steroid hormone action: Transcription factors, proto-oncogenes, and the cascade model for steroid regulation of gene expression. Crit. Rev. Eukaryot. Gene Expr. 2:19–63.
Lanza, V., Palazzadriano, M., Scardulla, C., Mercadante, S., Valdes, L., and Bellanca, G. (1987). Hemodynamics, prolactin and catecholamine levels during hemorrhagic shock in dogs pretreated with a prolactin inhibitor (bromocriptine). Pharmacol. Res. Commun. 19:307–318.
Levine, B., Kalman, J., Mayer, L., Fillit, H.M., and Packer, M. (1990). Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N. Engl. J. Med. 323:236–241.
Luo, S., Martel, C., Chen, C., Labrie, C., Candas, B., Singh, S.M., and Labrie, F. (1997). Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity. Urology 50:913–919.
Marshall, J.C. (1999). Organ dysfunction as an outcome measure in clinical trials. Eur. J. Surg. Suppl. 62–67.
Martel, C., Labrie, C., Belanger, A., Gauthier, S., Merand, Y., Li, X., Provencher, L., Candas, B., and Labrie, F. (1998). Comparison of the effects of the new orally active antiestrogen EM-800 with ICI 182 780 and toremifene on estrogen-sensitive parameters in the ovariectomized mouse. Endocrinology 139:2486–2492.
McGwin, G., Jr., George, R.L., Cross, J.M., Reiff, D.A., Chaudry, I.H., and Rue, L.W., III (2002). Gender differences in mortality following burn injury. Shock 18:311–315.
Meyers, M.J., Sun, J., Carlson, K.E., Marriner, G.A., Katzenellenbogen, B.S., and Katzenellenbogen, J.A. (2001). Estrogen receptor-beta potency-selective ligands: Structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J. Med. Chem. 44:4230–4251.
Miyao, Y., Yasue, H., Ogawa, H., Misumi, I., Masuda, T., Sakamoto, T., and Morita, E. (1993). Elevated plasma interleukin-6 levels in patients with acute myocardial infarction. Am. Heart J. 126:1299–1304.
Mize, A.L., Shapiro, R.A., and Dorsa, D.M. (2003). Estrogen receptor-mediated neuroprotection from oxidative stress requires activation of the mitogen-acti-vated protein kinase pathway. Endocrinology 144:306–312.
Mizushima, Y., Wang, P., Jarrar, D., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000). Estradiol administration after trauma-hemorrhage improves cardiovascular and hepatocellular functions in male animals. Ann. Surg. 232:673–679.
Morales-Montor, J., Chavarria, A., De Leon, M.A., Del Castillo, L.I., Escobedo, E.G., Sanchez, E.N., Vargas, J.A., Hernandez-Flores, M., Romo-Gonzalez, T., and Larralde, C. (2004). Host gender in parasitic infections of mammals: An evaluation of the female host supremacy paradigm. J. Parasitol. 90:531–546.
Muller, V., Losonczy, G., Heemann, U., Vannay, A., Fekete, A., Reusz, G., Tulassay, T., and Szabo, A.J. (2002). Sexual dimorphism in renal ischemia-reperfusion injury in rats: Possible role of endothelin. Kidney Int. 62:1364–1371.
Nathens, A.B., and Marshall, J.C. (1996). Sepsis, SIRS, and MODS: What’s in a name? World J. Surg. 20:386–391.
Neill, J.D. (1970). Effect of “stress” on serum prolactin and luteinizing hormone levels during the estrous cycle of the rat. Endocrinology 87:1192–1197.
Neill, J.D. (1972). Sexual differences in the hypothalamic regulation of prolactin secretion. Endocrinology 90:1154–1159.
Neill, J.D., and Smith, M.S. (1974). Pituitary-ovarian interrelationships in the rat. Curr. Top. Exp. Endocrinol. 2:73–106.
Nestler, J.E., Clore, J.N., and Blackard, W.G. (1991). Metabolism and actions of dehy-droepiandrosterone in humans. J. Steroid Biochem. Mol. Biol. 40:599–605.
O’Neill, P.J., Ayala, A., Wang, P., Ba, Z.F., Morrison, M.H., Schultze, A.E., Reich, S.S., and Chaudry, I.H. (1994). Role of Kupffer cells in interleukin-6 release following trauma-hemorrhage and resuscitation. Shock 1:43–47.
Oberholzer, A., Keel, M., Zellweger, R., Steckholzer, U., Trentz, O., and Ertel, W. (2000). Incidence of septic complications and multiple organ failure in severely injured patients is sex specific. J. Trauma 48:932–937.
Occhiato, E.G., Guarna, A., Danza, G., and Serio, M. (2004). Selective non-steroidal inhibitors of 5alpha-reductase type 1. J. Steroid Biochem. Mol. Biol. 88:1–16.
Offner, P.J., Moore, E.E., and Biffl, W.L. (1999). Male gender is a risk factor for major infections after surgery. Arch. Surg. 134:935–938.
Olsen, N.J., and Kovacs, W.J. (2001). Effects of androgens on T and B lymphocyte development. Immunol. Res. 23:281–288.
Orshal, J.M., and Khalil, R.A. (2004). Gender, sex hormones, and vascular tone. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286:R233–R249.
Pare, G., Krust, A., Karas, R.H., Dupont, S., Aronovitz, M., Chambon, P., and Mendelsohn, M.E. (2002). Estrogen receptor-alpha mediates the protective effects of estrogen against vascular injury. Circ. Res. 90:1087–1092.
Remmers, D.E., Wang, P., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (1997). Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males. Am. J. Physiol. 273:H2919–H2925.
Remmers, D.E., Cioffi, W.G., Bland, K.I., Wang, P., Angele, M.K., and Chaudry, I.H. (1998a). Testosterone: The crucial hormone responsible for depressing myocardial function in males after trauma-hemorrhage. Ann. Surg. 227:790–799.
Remmers, D.E., Wang, P., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (1998b). Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output. Ann. Surg. 227:112–119.
Samy, T.S., Schwacha, M.G., Cioffi, W.G., Bland, K.I., and Chaudry, I.H. (2000). Androgen and estrogen receptors in splenic T lymphocytes: Effects of flutamide and trauma-hemorrhage. Shock 14:465–470.
Samy, T.S., Knoferl, M.W., Zheng, R., Schwacha, M.G., Bland, K.I., and Chaudry, I.H. (2001). Divergent immune responses in male and female mice after trauma-hemorrhage: Dimorphic alterations in T lymphocyte steroidogenic enzyme activities. Endocrinology 142:3519–3529.
Samy, T.S., Zheng, R., Matsutani, T., Rue, L.W., III, Bland, K.I., and Chaudry, I.H. (2003). Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: Enhanced local synthesis of 17beta-estradiol. Am. J. Physiol. Cell Physiol. 285:C139–C149.
Schneider, C.P., Schwacha, M.G., Samy, T.S., Bland, K.I., and Chaudry, I.H. (2003). Androgen-mediated modulation of macrophage function after trauma-hemorrhage: Central role of 5alpha-dihydrotestosterone. J. Appl. Physiol. 95:104–112.
Schroder, J., Kahlke, V., Staubach, K.H., Zabel, P., and Stuber, F. (1998). Gender differences in human sepsis. Arch. Surg. 133:1200–1205.
Schroder, J., Kahlke, V., Book, M., and Stuber, F. (2000). Gender differences in sepsis: Genetically determined? Shock 14:307–310.
Scobie, G.A., Macpherson, S., Millar, M.R., Groome, N.P., Romana, P.G., and Saunders, P.T. (2002). Human oestrogen receptors: Differential expression of ER alpha and beta and the identification of ER beta variants. Steroids 67:985–992.
Shimizu, T., Choudhry, M.A., Szalay, L., Rue, L.W., III, Bland, K.I., and Chaudry, I.H. (2004). Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287:R386–R390.
Shimizu, T., Szalay, L., Choudhry, M.A., Schwacha, M.G., Rue, L.W., III, Bland, K.I., and Chaudry, I.H. (2005). Mechanism of salutary effects of androstenediol on hepatic function after trauma-hemorrhage: Role of endothelial and inducible nitric oxide synthase. Am. J. Physiol. Gastrointest. Liver Physiol. 288:G244–G250.
Smithson, G., Couse, J.F., Lubahn, D.B., Korach, K.S., and Kincade, P.W. (1998). The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis. J. Immunol. 161:27–34.
Stauffer, S.R., Coletta, C.J., Tedesco, R., Nishiguchi, G., Carlson, K., Sun, J., Katzenellenbogen, B.S., and Katzenellenbogen, J.A. (2000). Pyrazole ligands: Structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists. J. Med. Chem. 43:4934–4947.
Tarnoky, K., and Nagy, S. (1983). Relationship to survival of catecholamine levels and dopamine-beta-hydroxylase activity in experimental haemorrhagic shock. Acta Physiol. Hung. 61:59–68.
Tremblay, A., Tremblay, G.B., Labrie, C., Labrie, F., and Giguere, V. (1998). EM-800, a novel antiestrogen, acts as a pure antagonist of the transcriptional functions of estrogen receptors alpha and beta. Endocrinology 139:111–118.
Verthelyi, D. (2001). Sex hormones as immunomodulators in health and disease. Int. Immunopharmacol. 1:983–993.
Wang, P., Ba, Z.F., Burkhardt, J., and Chaudry, I.H. (1993). Trauma-hemorrhage and resuscitation in the mouse: Effects on cardiac output and organ blood flow. Am. J. Physiol. 264:H1166–H1173.
Whitnall, M.H., Wilhelmsen, C.L., McKinney, L., Miner, V., Seed, T.M., and Jackson, W.E., III (2002). Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice. Immunopharmacol. Immunotoxicol. 24:595–626.
Wichmann, M.W., Zellweger, R., DeMaso, C.M., Ayala, A., and Chaudry, I.H. (1996a). Enhanced immune responses in females, as opposed to decreased responses in males following haemorrhagic shock and resuscitation. Cytokine 8:853–863.
Wichmann, M.W., Zellweger, R., DeMaso, C.M., Ayala, A., and Chaudry, I.H. (1996b). Mechanism of immunosuppression in males following trauma-hemorrhage. Critical role of testosterone. Arch. Surg. 131:1186–1191.
Wichmann, M.W., Ayala, A., and Chaudry, I.H. (1997). Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage. Am. J. Physiol. 273:C1335–C1340.
Wichmann, M.W., Inthorn, D., Andress, H.J., and Schildberg, F.W. (2000). Incidence and mortality of severe sepsis in surgical intensive care patients: The influence of patient gender on disease process and outcome. Intensive Care Med. 26:167–172.
Wunderlich, F., Benten, W.P., Lieberherr, M., Guo, Z., Stamm, O., Wrehlke, C., Sekeris, C.E., and Mossmann, H. (2002). Testosterone signaling in T cells and macrophages. Steroids 67:535–538.
Xu, Y.X., Ayala, A., and Chaudry, I.H. (1998). Prolonged immunodepression after trauma and hemorrhagic shock. J. Trauma 44:335–341.
Yamauchi-Takihara, K., Ihara, Y., Ogata, A., Yoshizaki, K., Azuma, J., and Kishimoto, T. (1995). Hypoxic stress induces cardiac myocyte-derived interleukin-6. Circulation 91:1520–1524.
Yang, S., Zheng, R., Hu, S., Ma, Y., Choudhry, M.A., Messina, J.L., Rue, L.W., III, Bland, K.I., and Chaudry, I.H. (2004). Mechanism of cardiac depression after trauma-hemorrhage: Increased cardiomyocyte IL-6 and effect of sex steroids on IL-6 regulation and cardiac function. Am. J. Physiol. Heart Circ. Physiol. 287:H2183–H2191.
Yao, Y.M., Redl, H., Bahrami, S., and Schlag, G. (1998). The inflammatory basis of trauma/shock-associated multiple organ failure. Inflamm. Res. 47:201–210.
Yokoyama, Y., Schwacha, M.G., Samy, T.S., Bland, K.I., and Chaudry, I.H. (2002). Gender dimorphism in immune responses following trauma and hemorrhage. Immunol. Res. 26:63–76.
Zellweger, R., Ayala, A., DeMaso, C.M., and Chaudry, I.H. (1995). Trauma-hemorrhage causes prolonged depression in cellular immunity. Shock 4:149–153.
Zellweger, R., Wichmann, M.W., Ayala, A., DeMaso, C.M., and Chaudry, I.H. (1996a). Prolactin: A novel and safe immunomodulating hormone for the treatment of immunodepression following severe hemorrhage. J. Surg. Res. 63:53–58.
Zellweger, R., Zhu, X.H., Wichmann, M.W., Ayala, A., DeMaso, C.M., and Chaudry, I.H. (1996b). Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis. J. Immunol. 157:5748–5754.
Zellweger, R., Wichmann, M.W., Ayala, A., and Chaudry, I.H. (1998). Metoclopramide: A novel and safe immunomodulating agent for restoring the depressed macrophage immune function after hemorrhage. J. Trauma 44:70–77.
Zellweger, R., Wichmann, M.W., Ayala, A., Stein, S., DeMaso, C.M., and Chaudry, I.H. (1997). Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males. Crit. Care Med. 25:106–110.
Zhang, C.C., and Shapiro, D.J. (2000). Activation of the p38 mitogen-activated protein kinase pathway by estrogen or by 4-hydroxytamoxifen is coupled to estrogen receptor-induced apoptosis. J. Biol. Chem. 275:479–486.
Zhang, Z., Maier, B., Santen, R.J., and Song, R.X. (2002). Membrane association of estrogen receptor alpha mediates estrogen effect on MAPK activation. Biochem. Biophys. Res. Commun. 294:926–933.
Zheng, R., Samy, T.S., Schneider, C.P., Rue, L.W., III, Bland, K.I., and Chaudry, I.H. (2002). Decreased 5alpha-dihydrotestosterone catabolism suppresses T lymphocyte functions in males after trauma-hemorrhage. Am. J. Physiol. Cell Physiol. 282:C1332–C1338.
Zhu, X.H., Zellweger, R., Ayala, A., and Chaudry, I.H. (1996). Prolactin inhibits the increased cytokine gene expression in Kupffer cells following haemorrhage. Cytokine 8:134–140.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Choudhry, M.A., Chaudry, I.H. (2006). Gender Dimorphism and the Use of Sex Steroid/Receptor Antagonist After Trauma. In: Welsh, C.J., Meagher, M.W., Sternberg, E.M. (eds) Neural and Neuroendocrine Mechanisms in Host Defense and Autoimmunity. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-48334-4_6
Download citation
DOI: https://doi.org/10.1007/978-0-387-48334-4_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-31411-2
Online ISBN: 978-0-387-48334-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)