Gender and Androgen Treatment Influence the Expression of Proto-oncogenes and Apoptotic Factors in Lacrimal and Salivary Tissues of MRL/lprMice

Abstract

The objectives of this study were to (1) determine whether Fas antigen, Fas ligand, p53, and proto-oncogene mRNAs may be detected in lacrimal and submandibular glands of the MRL/lprmouse model of Sjögren's syndrome, and (2) examine whether gender and androgen or cyclophosphamide therapy influence the mRNA expression of these apoptotic factors. Tissues were obtained from treated or untreated MRL/lprmice after the onset of disease and processed for the analysis of mRNAs by RT-PCR and Southern blot hybridization. Our results demonstrated that (1) Fas antigen (exons 1 → 2 or 3 → 7+), Fas ligand, c-myb, c-myc, bcl-2, Bax, p53, and androgen receptor (AR) mRNAs are present in exocrine tissues of MRL/lprmice; (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 male 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 mice; and (3) testosterone or cyclophosphamide treatment led to a significant (P< 0.05) decline in the mRNA levels of c-myb, bcl-2, and/or AR, but an increase (P< 0.05) in the mRNA amount of Bax, in lacrimal, but not in salivary, glands of female mice. These findings demonstrate that gender-associated differences exist in the expression of apoptotic factor mRNAs in exocrine tissues of autoimmune mice and that some of these differences appear to be due to the influence of androgens.