Hepatic microsomal estrogen metabolism was analyzed in the (New Zealand black x New Zealand white)F, ([NZB X NZWIF,) murine model of systemic lupus erythematosus. Both the estrogen 2-hydroxylase activity (per mg microsomal protein) and the hepatic cytochrome P-450 content were higher in premorbid (NZB X NZW)F, mice, as compared with similarly aged nonautoimmune mice. However, these differences were not associated with alterations in the relative formation of the 2-hydroxylated and the 16cu-hydroxylated metabolites. The development of overt nephritis was associated with a decrease in estrogen metabolic activity, but not with any alteration in the distribution of estrogen metabolites. Thus, estrogen metabolism was not altered in premorbid (NZB X NZW)F, mice in a manner that would result in abnormal retention of hormonally active metabolites.
Alterations in estrogen metabolism have been observed in patients with systemic lupus erythematosus (SLE). Both male and female SLE patients have an increased rate of estradiol 16a-hydroxylation, while female SLE patients have a decreased rate of estrogen 2-hydroxylation (1). The net effect of these alterations From the Division of Rheumatology, Department of Medicine, State University of New York at Buffalo, and the Veterans Administration Medical Center. Buffalo, New York.