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Effects of an Aromatase Inhibitor on Thymus and Kidney and on Oestrogen Receptors in Female MRL/MP-lpr/lpr Mice
Greenstein, B.D.; Dhaher, Y.Y.; Bridges, E. de F.; Keser, G.; Khamashta, M.A.; Etherington, J.; Greenstein, A.S.; Coates, P.J.; Hall, P.A.; Hughes, G.R.V.
The effects of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), which blocks oestrogen formation, have been studied in female MRL/MP- lpr/lpr mice which are a model of SLE. At 11.5 weeks, mice were implanted subcutaneously either with empty Silastic implants or with implants containing 25 mg 4-OHA. At 15 weeks, they were sacrificed by decapitation and liver, thymus, kidneys and uterus taken for wet weight, histology and measurement of cytosolic and nuclear oestrogen receptors. Thymus weights were significantly lower in 4-OHA-treated mice although uterus weights were similar in both groups. Also, whereas thymuses from control-treated mice were packed with plasma cells with abundant cytoplasm, those from 4-OHA-treated mice contained T cells with large nuclei. Relative oestrogen receptor abundances were: uterus > liver > thymus, although cytosolic receptors could not be detected in thymus cytosols of MRL mice unless they were treated with the aromatase inhibitor. In kidney, there was histological evidence that inflammation was limited to mesangium in 4-OHA-treated mice. These results support the hypothesis that oestrogens may be involved in the aetiology of murine SLE and provide data suggesting that substances which block oestrogen production in vivo may be useful to treat certain forms of SLE.