Impaired estrogen priming of progesterone receptors in uterus of MRL/MP-lpr/lpr mice, a model of systemic lupus erythematosus (SLE)

Estrogens exacerbate the autoimmune disease SLE and progesterone is immunop rotective. Estrogens increase synthesis of progesterone receptors (PR) and it is hypothesized that this physiological balance may be impaired in SLE, To test this, cytosolic PR were measured in hypothalamus, thymus and uterus from 6-week-old female ovariectomized BALB/c and MRL/MP-lpr/lpr mice 48 h after s.c. injection of estradiol benzoate (3.2 mu g/0.1 ml; OB) in peanut oil or 0.1 ml peanut oil alone. PR were measured using [H-3]ORG 2058, which does not bind to corticosteroid-binding globulin (CBG), and bound and free ligand were separated using minicolumns of Sephadex LH2O at 0 degrees C, P R were measured in cytosols from hypothalamus and uterus of oil-treated BAL B/c mice, but were undetectable in thymus, whereas receptors were measurabl e in all three tissues of MRL mice. There was a significantly greater primi ng effect of OB on PR in uterus of BALB/c mice, but not in hypothalamus, an d PR became detectable in thymus cytosols from BALB/c mice. Also, the appar ent affinity of the binding reaction between [H-3]ORG 2058 and PR was signi ficantly higher than those measured in other tissues in hypothalamic cytoso ls of both strains. These results suggest that there is an impairment of es trogen priming of progesterone receptors in uterus and perhaps thymus of MR L mice. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.