Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model.
The specific roles of estrogen receptor (ER) subtypes alpha and beta in mediating estrogen's influences on lupus autoimmunity are unknown. Herein we found that ovariectomized NZB/NZW F1 mice treated with propyl pyrazole triol (ERalpha-selective agonist) had significantly shorter survival, earlier development of albuminuria, higher serum concentrations of total IgG and prolactin, increased serum levels of anti-DNA IgG3, IgG2a and IgG2b and decreased anti-DNA IgG1 level compared to vehicle controls. In contrast, diarylpropionitrile (ERbeta-selective agonist) administration significantly decreased serum anti-DNA IgG2b level but did not significantly affect serum levels of other anti-DNA IgG subclasses, serum total IgG or prolactin concentration, mortality or the occurrence of albuminuria. These findings suggest that ERalpha activation plays the predominant and immunostimulatory role in estrogen-mediated modulation of lupus while ERbeta activation appears to have a slightly immunosuppressive effect on this disease. ERalpha activation coincidentally increased serum prolactin concentrations and may accelerate lupus disease activity also through this mechanism.
Li
Jing
J
Department of Endocrinology, the First Hospital Affiliated to China Medical University, Shenyang, 110001, P.R. China.
McMurray
Robert W
RW
D000419:Albuminuria / Q000652:urine; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000819:agonists; D005260:Female; D007107:Immune System / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols; D011388:Prolactin / Q000097:blood; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000819:agonists*; D016019:Survival Analysis
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D000974:Antibodies, Antinuclear; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007074:Immunoglobulin G; D007155:Immunologic Factors; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D011960:Receptors, Estrogen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C074283:estradiol 3-benzoate; D004958:Estradiol; D011388:Prolactin