In vivo effects of sex steroids on lymphocyte responsiveness and immunoglobulin levels in humans.
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.
Giltay
E J
EJ
Research Institute for Endocrinology, Reproduction, and Metabolism, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. giltay@dds.nl
Fonk
J C
JC
von Blomberg
B M
BM
Drexhage
H A
HA
Schalkwijk
C
C
Gooren
L J
LJ
D000293:Adolescent; D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D017373:Cyproterone Acetate / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000097:blood; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D013739:Testosterone / Q000494:pharmacology; D014189:Transsexualism
D000726:Androgen Antagonists; D016207:Cytokines; D012739:Gonadal Steroid Hormones; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D019707:Receptors, Chemokine; D013739:Testosterone; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate