Gap junction connexin genes cx26 and cx43 are differentially regulated by ovarian steroid hormones in rat endometrium

In rat endometrium, expression of gap junction connexin-26 (cx26) in the ep ithelium and cx43 in the uterine stroma is suppressed by progesterone befor e implantation. For further study of connexin gene regulation we analyzed e xpression of cx26, cx43, and cx32 in the endometrium of ovariectomized rats treated with different ratios of 17 beta-estradiol (E-2) and progesterone (P). A hormonal ratio of E-2 to P that mimics conditions during pregnancy ( 0.1 mu g E-2 and 4 mg P) suppressed expression of cx26 and cx43. By changin g the ratio to higher E-2 levels (1 mu g E-2), cx26, in contrast to cx43, w as not suppressed even by application of a high P concentration (10 mg). Ti me-course experiments supplying E-2 alone led to an early gene response of cx26 within 3 h, whereas induction of cx43 transcripts was not detected unt il 14 h after E-2 treatment. Simultaneous application of the antiestrogen I CI 182780 abolished E-2-mediated induction of both connexins. No hormonal r egulation of cx32 could be detected. As already shown for cx43 gene inducti on in the myometrium, E-2-mediated induction of cx26 expression in the endo metrium also required newly synthesized transcription factors. It can be co ncluded that only a hormonal ratio resembling conditions during pregnancy i s able to suppress the expression of both cx26 and cx43 and that cx26 gene expression is induced earlier by E-2 and is likely to be more sensitive to a shift in the E-2 to P ratio than cx43.