In vivo effects of sex steroids on lymphocyte responsiveness and immunoglobulin levels in humans

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 4; pp. 1648 - 1657
• Main Authors: GILTAY, E. J, FONK, J. C. M, VON BLOMBERG, B. M. E, DREXHAGE, H. A, SCHALKWIJK, C, GOOREN, L. J. G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-04-2000
• Subjects: Adolescent; Adult; AIDS/HIV; Analysis of the immune response. Humoral and cellular immunity; Androgen Antagonists - pharmacology; Biological and medical sciences; CD4 Lymphocyte Count; Cyproterone Acetate - pharmacology; Cytokines - biosynthesis; Ethinyl Estradiol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gonadal Steroid Hormones - pharmacology; Humans; Immunobiology; Immunoglobulin G - blood; Immunoglobulin M - blood; Immunoglobulins - blood; Male; Middle Aged; Miscellaneous; Receptors, Chemokine - blood; Regulatory factors and their cellular receptors; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; Testosterone - pharmacology; Transsexualism; Human; Natural killer cell; Numeration; Immunoglobulins; Transsexualism; Cytokine; Hormonal regulation; Sex; Adult; Sex steroid hormone; Comparative study; Blood plasma
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.4.1648

The female predominance in several autoimmune diseases suggests a role for sex steroid hormones in disease susceptibility. We therefore investigated to what extent sex hormones would influence immune responsiveness. We analyzed T helper type 1 (TH1) and type 2 cytokine patterns, chemokine receptor expression (n = 2 x 10), and Ig levels (n = 2 x 25) in transsexual men and women before and after 4 months of cross-sex hormone administration. Antithyroperoxidase levels were compared between 186 transsexual males (treated >5 yr with estrogens) and 186 male controls. In men, estrogens plus antiandrogens increased free cortisol levels in 24-h urine samples, decreased natural killer cell numbers, and slightly inhibited the mitogen-induced interferon-gamma/interleukin-4 ratio, but up-regulated the expression of TH1-associated chemokine receptors, CCR1, CXCR3, and CCR5. Conversely, in women, androgens slightly decreased free cortisol levels in 24-h urine samples and enhanced the mitogen-induced interferon-gamma/interleukin-4 ratio and tumor necrosis factor-alpha production. At the single cell level no TH 1/TH2 shifts were found. Remarkably, up-regulation of TH1 cytokines was accompanied by down-regulation of CCR1, CXCR3, and CCR5 expression. Neither CD4+ lymphocyte numbers nor IgG, IgM, and antithyroperoxidase levels, although higher in women then in men, were affected by cross-sex hormonal treatment. These results demonstrate that the capacity to develop a TH1 phenotype of peripheral blood lymphocytes is stimulated by androgens and is slightly inhibited by estrogens. These changes may be direct or indirect through the effects on other hormones.