Differential expression of activator protein-1 transcription factors in pregnant rat myometrium

Abstract

While the AP-1 (activator protein-1) genes c-fos and c-jun have been implicated in the expression of myometrial genes associated with the onset of labor, there are no data concerning the role of other members of this family of transcription factors. To address this issue, we defined the expression and hormonal regulation of AP-1 genes in the rat myometrium during pregnancy and labor. Tissue was collected on Days 12, 15, 17, 19, 21, 22, and 23 (labor) and 1 day postpartum. Expression of c-fos, fosB, fra-1, fra-2, and junB was low during early gestation, with a 5- to 10-fold increase on Day 23 during labor, and returned to low levels 1 day postpartum. In contrast, the levels of c-jun and junD remained relatively constant throughout gestation. Administration of progesterone (P4; 16 mg/kg s.c./day) beginning on Day 20 (to maintain elevated plasma P4 levels) prevented the onset of labor and blocked the expected rise in c-fos, fosB, fra-1, fra-2, and junB expression on Day 23. In contrast, administration of the progesterone receptor antagonist RU486 (10 mg/kg s.c.) on Day 19 induced preterm labor and a premature increase in mRNA levels of c-fos, fra-1, fra-2, and junB. In unilaterally pregnant rats, stretch imposed by the growing fetus was found to increase the expression of c-fos, fosB, fra-1, fra-2, and junB only in the gravid horn on the day of labor. These data raise the possibility that AP-1 transcription factors integrate endocrine and mechanical signals, leading to myometrial gene expression required for uterine remodeling and the initiation of labor.