GENDER AND ANDROGEN TREATMENT INFLUENCE THE EXPRESSION OF PROTOONCOGENES AND APOPTOTIC FACTORS IN LACRIMAL AND SALIVARY TISSUES OF MRL LPR MICE/

The objectives of this study were to (1) determine whether Fas antigen , Fas ligand, p53, and proto-oncogene mRNAs may be detected in lacrima l and submandibular glands of the MRL/lpr mouse model of Sjogren's syn drome, and (2) examine whether gender and androgen or cyclophosphamide therapy influence the mRNA expression of these apoptotic factors. Tis sues were obtained from treated or untreated MRL/lpr mice after the on set of disease and processed for the analysis of mRNAs by RT-PCR and S outhern blot hybridization. Our results demonstrated that (1) Fas anti gen (exons 1 --> 2 or 3 --> 7+), Fas ligand, c-myb, c-myc, bcl-2, Bar, p53, and androgen receptor (AR) mRNAs are present in exocrine tissues of MRL/lpr mice; (2) the amounts of c-myb, c-myc, bcl-2, p53, and AR mRNA are higher (P < 0.05) and the level of Fas antigen (exons 1 --> 2 ) mRNA is lower (P < 0.05) in lacrimal glands of female compared to ma le mice. In contrast, the content of c-myb and p53 mRNA is greater (P < 0.05) in submandibular tissues of female relative to those of male m ice; and (3) testosterone or cyclophosphamide treatment led to a signi ficant (P < 0.05) decline in the mRNA levels of c-myb, bcl-2, and/or A R, but an increase (P < 0.05) in the mRNA amount of Bar, in lacrimal, but not in salivary, glands of female mice. These findings demonstrate that gender-associated differences exist in the expression of apoptot ic factor mRNAs in exocrine tissues of autoimmune mice and that some o f these differences appear to be due to the influence of androgens. (C ) 1998 Academic Press.