Immunomodulatory actions of gonadal steroids may be mediated by gonadotropin-releasing hormone.
Estrogens are considered to be immunostimulatory, whereas androgens are considered to be immunosuppressive. We hypothesized that the divergent actions of gonadal steroids on the immune system may be mediated indirectly, via their potent divergent feedback effects on the hypothalamic hormone GnRH, which is itself immunostimulatory. We used the GnRH-deficient HPG/Bm mouse in an effort to disentangle the effects of gonadal steroids from the effects of GnRH. We randomized GnRH-deficient mice and their GnRH-sufficient littermates to receive androgens, estrogens, or GnRH. We subsequently measured B and T cell proliferative responses to mitogen and serum IgG levels. We demonstrate that estrogens exert stimulatory effects on B cell proliferation and serum IgG levels in the presence of GnRH but not in the absence of GnRH. Testosterone exerts suppressive effects on B cell function in the presence of GnRH but not in its absence. Androgens and estrogens exerted divergent actions on T cell function irrespective of the presence and absence of GnRH, although responses were markedly attenuated in GnRH-deficient mice. Our data suggest that the immunostimulatory effects of estrogen and the immunosuppressive effects of androgens on B cell function may be mediated indirectly via GnRH.
Jacobson
Jill D
JD
Section of Endocrinology, Children's Mercy Hospital, University of Missouri-Kansas Cisty School of Medicine, Kansas City, Missouri 64108, USA. jjacobson@cmh.edu
Ansari
Mansoor A
MA
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000728:Androgens / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004967:Estrogens / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009919:Orchiectomy; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D011966:Receptors, LHRH / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology
D000276:Adjuvants, Immunologic; D000728:Androgens; D004967:Estrogens; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone