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Sex Hormones and the Genesis of Autoimmunity

Lindsay S. Ackerman, MD
Arch Dermatol. 2006;142(3):371-376. doi:10.1001/archderm.142.3.371.
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Background  The sexually dimorphic prevalence of autoimmune disease remains one of the most intriguing clinical observations among this group of disorders. While sex hormones have long been recognized for their roles in reproductive functions, within the past 2 decades scientists have found that sex hormones are integral signaling modulators of the mammalian immune system. Sex hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation.

Observations  English-language literature from the last 10 years was reviewed to examine the relationship between sex hormones and the function of the mammalian immune system. Approximately 50 publications were included in this review, and the majority were controlled trials with investigator blinding that compared both male and female diseased and normal subjects. The review provided basic knowledge regarding the broad impact of sex hormones on the immune system and how abnormal sex hormone expression contributes to the development and maintenance of autoimmune phenomena, with a focus on systemic lupus erythematosus, as models of “lupus-prone” mice are readily available.

Conclusions  Sex hormones affect the function of the mammalian immune system, and sex hormone expression is different in patients with systemic lupus erythematosus than in healthy subjects. Sex hormones play a role in the genesis of autoimmunity. Future research may provide a therapeutic approach that is capable of altering disease pathogenesis, rather than targeting disease sequelae.

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Signal transduction in T cells bound to antigen (Ag) and exposed to estrogen (E). A, Signal transduction in healthy T cells. B, Lupus T cells with the same Ag burden as shown in A. Calcium (Ca++) and calcineurin expression are enhanced in these cells. TCR indicates T-cell receptor; IP3, inositol-3-phosphate; PLC, phospholipase C; DAG, diacylglycerol; ER, estrogen receptor; NFAT, nuclear factor of activated T cells; and PO4, phosphate.

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