Gender- and androgen-related influence on the expression of proto-oncogeneand apoptotic factor mRNAS in lacrimal glands of autoimmune and non-autoimmune mice

Our previous studies have shown that the mRNA levels of c-myb, c-myc, bcl-2 and p53 are higher, and partial Fas antigen (i.e. exons 1-2) lower, in lac rimal tissues of female, as compared to male, MRL/lpr mice, which are a mod el of Sjogren's syndrome. We have also found that this gender-related diffe rence in bcl-2 and c-myb expression appears to be due to the influence of a ndrogens. To extend these findings, we sought to determine: first, whether these gender- and/or hormone-associated variations in mRNA content are uniq ue to MRL/lpr mice, or are also present in lacrimal glands of other murine strains, including autoimmune NZB/NZW F1 (F1) and non-obese diabetic (NOD), as well as non-autoimmune C3H/HeJ (C3H) and BALB/c, mice; and second, whet her the levels of these apoptotic factor mRNAs are altered in lacrimal tiss ues of mice (i.e. testicular feminized (Tfm) with dysfunctional androgen re ceptors, as compared to glandular amounts in their 'normal' controls (i.e. Tabby). Lacrimal tissues were obtained from adult mice, which were either u ntreated or treated with placebo or testosterone for 21 days. Glands were p rocessed for the analysis of proto-oncogene mRNAs by RT-PCR (at exponential phase of amplification) and data were standardized to the corresponding le vels of beta-actin mRNA. Our results demonstrate that Fas antigen, Fas liga nd, c-myb, c-myc, bcl-2; Bar and p53 mRNAs are present in lacrimal tissues of Fl, NOD, C3H, BALB/c, Tabby and Tfm mice. The relative levels of Fas ant igen mRNA are consistently higher in glands of males, whereas amounts of bc l-2 mRNA are greater in tissues of F1, C3H and BALB/c females. Testosterone administration induced a significant increase in the lacrimal gland conten t of Bar mRNA, but a striking decrease in the lacrimal tissue level of bcl- 2 mRNA in F1 and C3H mice. Lacrimal glands of Tfm mice contained elevated a mounts of bcl-2 mRNA, as compared to values in tissues of their Tabby contr ols. In summary, our findings show that fundamental gender-related differen ces exist in the expression of genes associated with programmed cell death in lacrimal glands of autoimmune and normal mice. In addition, some of thes e differences may be due, at least in part, to the effect of androgens. (C) 1999 Elsevier Science Ltd, All rights reserved.