Androgen and Estrogen Receptors in Splenic T Lymphocytes: Effects of Flutamide and Trauma-Hemorrhage

Samy, T. S. Anantha; Schwacha, Martin G.; Cioffi, William G.; Bland, Kirby I.; Chaudry, Irshad H.

doi:10.1097/00024382-200014040-00008

Cited by 77 publications

(59 citation statements)

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“…Consistent with immune suppression in males following burn plus alcohol, flutamide had no effect on immune responses in sham animals but restored cellular proliferation and the DTH response in burned male mice [33]. Flutamide did not increase circulating levels of testosterone [33], but it did increase estrogen levels (KAN Messingham, MA Emanuele, and EJ Kovacs unpublished observations) as well as estrogen receptor expression following burn [96]. Additionally, as mentioned earlier, burn causes a rise in estrogen levels in female mice to those resembling pregnancy (immunosuppressive) where levels of estrogen in burned male mice reach low levels such as that of sham females (immunostimulatory) [75].…”

Section: Burn and Co-morbidity Factorsmentioning

confidence: 88%

“…Interestingly, no differences in the expression of androgen and estrogen receptors in male and female mice following trauma or following burn [96]. However, pretreatment of flutamide increased the expression of ER in T cells in animals following both sham and trauma-hemorrhage [96]. IL-6 is lower in normal male mice following traumahemorrhage, but treatment with flutamide increased production of IL-6 levels in male mice after trauma-hemorrhage to that of sham levels suggesting increases in ER expression may be protective in males in certain injuries.…”

Section: Mechanisms Sectionmentioning

confidence: 99%

“…The major effects of estrogen are mediated through two different receptors, ER-α and ER-β, which are expressed in immune cells [96]. Interestingly, no differences in the expression of androgen and estrogen receptors in male and female mice following trauma or following burn [96]. However, pretreatment of flutamide increased the expression of ER in T cells in animals following both sham and trauma-hemorrhage [96].…”

Section: Mechanisms Sectionmentioning

confidence: 99%

Section: Mechanisms Sectionmentioning

confidence: 99%

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Sex differences and estrogen modulation of the cellular immune response after injury

Bird¹,

Karavitis²,

Kovacs³

2008

Cellular Immunology

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Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testosterone can positively or negatively regulate the cellular immune response either by aiding in resolution or by compounding the morbidity and mortality. It is apparent that the hormonal dysregulation is dependent not only on the type of injury sustained but also the amount of circulating hormones. Therefore, it may be possible to design sex-specific therapies to improve immunological function and patient outcome.

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Section: Burn and Co-morbidity Factorsmentioning

confidence: 88%

Section: Mechanisms Sectionmentioning

confidence: 99%

Section: Mechanisms Sectionmentioning

confidence: 99%

Section: Mechanisms Sectionmentioning

confidence: 99%

See 2 more Smart Citations

Sex differences and estrogen modulation of the cellular immune response after injury

Bird¹,

Karavitis²,

Kovacs³

2008

Cellular Immunology

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“…The ovary is the primary site of estrogen synthesis in females, and despite that, the enzymes involved in estrogen metabolism are also present in peripheral tissues, including spleen and the T lymphocytes (21,37). The presence of steroidogenic enzymes, especially in the T lymphocytes, suggests a role for local synthesis of E2 for interaction with the estrogen receptor (ER) present in the cells (39) and the production of cytokines as needed. E2 is a highly potent regulatory sex steroid involved in a variety of metabolic functions.…”

mentioning

confidence: 99%

Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: enhanced local synthesis of 17β-estradiol

Samy

Zheng

Matsutani

et al. 2003

American Journal of Physiology-Cell Physiology

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and resuscitation (TH) produces profound immunodepression and enhances susceptibility to sepsis in males but not in proestrus females, suggesting gender dimorphism in the immune responses. However, the mechanism responsible for the maintenance of immune functions in proestrus females after TH is unclear. Splenic T lymphocytes express receptors for estrogen (ER), contain enzymes involved in estrogen metabolism, and are the major source of cytokine production; the metabolism of 17␤-estradiol was assessed in the splenic T lymphocytes of proestrus and ovariectomized mice by using appropriate substrates after TH. Analysis for aromatase and 17␤-hydroxysteroid dehydrogenases indicated increased 17␤-estradiol synthesis and low conversion into estrone in T lymphocytes of proestrus but not of ovariectomized mice. The effect of 17␤-estradiol on T lymphocyte cytokine release was reliant on ER expressions. This was apparent in the differences of ER expression, especially that of ER-␤, and an association between increased 17␤-estradiol synthesis and sustained release of IL-2 and IL-6 in T lymphocytes of proestrus females after TH. Because 17␤-estradiol is able to regulate cytokine genes, and the splenic T lymphocyte cytokine releases is altered after TH, continued synthesis of 17␤-estradiol in proestrus females appears to be responsible for the maintenance of T lymphocyte cytokine release associated with the protection of immune functions after TH. inflammation; immune suppression; steroid synthesis; T lymphocytes; cytokines THE INFLUENCE OF GENDER on immune functions has been recognized for many years, and in general, women are known to develop enhanced humoral responses compared with men and are more prone to autoimmune diseases (9,12,20). Trauma-hemorrhage and resuscitation (TH) produce severe impairment of both immune and cardiovascular functions (51,56,57). Although depression of cellular immunity occurs very early following TH, the loss in immune functions persists for a prolonged period, which may lead to subsequent sepsis with high mortality rates (43, 56). The immune depression is pronounced in males and ovariectomized females (OVX) after TH compared with proestrus females (54, 55). Moreover, immune functions in males and OVX females can be restored by the administration of 17␤-estradiol (E2) after TH (16-18). Thus gender dimorphism is obvious in the loss of immune functions after TH, implicating a major role for sex steroid hormones (2, 4).Steroid hormones regulate immune functions in vivo, and the mechanisms involve not only the control of cytokine gene transcription by the classic steroid hormone-receptor complex but also the tissue-specific metabolism of sex steroids (11,21,24,29,33,36,47). Among the sex steroids, estrogen is demonstrated to protect immune functions after TH because proestrus females are not immunodepressed compared with male and OVX mice. Furthermore, the depressed immune functions in males and OVX females after TH can be normalized by parenteral E2 administration (16-18). The ovary is the prima...

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Attenuation of Vascular Endothelial Dysfunction by Testosterone Receptor Blockade After Trauma and Hemorrhagic Shock

Wang²,

Koo³

et al. 2001

Arch Surg

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Androgen and Estrogen Receptors in Splenic T Lymphocytes: Effects of Flutamide and Trauma-Hemorrhage

Cited by 77 publications

References 0 publications

Sex differences and estrogen modulation of the cellular immune response after injury

Sex differences and estrogen modulation of the cellular immune response after injury

Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: enhanced local synthesis of 17β-estradiol

Attenuation of Vascular Endothelial Dysfunction by Testosterone Receptor Blockade After Trauma and Hemorrhagic Shock

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