Estrogen induces the development of autoantibodies and promotes salivary gland lymphoid infiltrates in normal mice.
There are important bidirectional interactions between the immune and the endocrine system. Sex hormones influence the immune system throughout life including postnatal and prenatal stages. For example, we find that administration of estrogen to normal mice markedly augments the ability of CD5+ B cells to express their autoimmune potential by producing increased numbers of plaque-forming cells (APFC) to bromelain-treated mouse erythrocytes (Br-ME). The effect of sex hormones on immune function at the most critical stage of development, the prenatal period, remains unstudied. We hypothesize that an imbalance of the in utero sex hormone microenvironment critically influences the fetal immune system. We have termed this influence immunological imprinting. After birth this imprinting could contribute to immune-mediated disorders. To test this hypothesis, we developed a mouse model in which normal mice were prenatally exposed to estrogens. In preliminary experiments, these mice produced higher numbers of APFC to Br-ME, particularly in the peritoneal cavity cell exudates. Furthermore, mice prenatally exposed to estrogens had accelerated development of autoimmune salivary gland lesions indistinguishable from Sjögren's syndrome (SS) in humans. Further experiments are warranted to confirm these findings. The prenatal effects of estrogen may have relevance for familial and neonatal autoimmune syndromes.
Ahmed
S A
SA
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.
Aufdemorte
T B
TB
Chen
J R
JR
Montoya
A I
AI
Olive
D
D
Talal
N
N
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000473:pathology; D001402:B-Lymphocytes / Q000473:pathology; D004195:Disease Models, Animal; D004967:Estrogens / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012466:Salivary Gland Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D012737:Sex Factors; D012859:Sjogren's Syndrome / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D001323:Autoantibodies; D004967:Estrogens