REGULATION OF TRANSCRIPTS ENCODING THE MYOMETRIAL GAP JUNCTION PROTEIN, CONNEXIN-43, BY ESTROGEN AND PROGESTERONE

In the rat, transcripts encoding the myometrial gap junction protein, connexin-43 (Cx-43), increase dramatically with the onset of labor in association with an increase in the ratio of estrogen to progesterone in plasma. We examined whether the level of Cx-43 transcripts might be regulated by these steroids in the rat myometrium. Administration of progesterone to late pregnant rats abolished the more than 12-fold increase in transcripts seen in control rats at term and blocked delivery of the fetuses. Treatment of rats on day 15 of gestation (when Cx-43 mRNA levels are low) with the progesterone antagonist RU486 resulted in a significant (2.5-fold) increase in transcripts within 9 h, with the maximal (5.6-fold) increase occurring between 24-48 h, and preterm delivery occurring between 48-72 h. Administration of a single dose of 17beta-estradiol (5 mug, sc) to nonpregnant rats resulted in a significant increase in Cx-43 transcripts within 3 h; these levels were increased 3-fold between 6-24 h, before falling to lower levels by 48 h. Progesterone (4 mg, sc) administration at the same time as estradiol significantly attenuated the estradiol response. Chronic estradiol administration (5 mug/12 h for 36 h) failed to maintain elevated levels of Cx-43 transcripts beyond 36 h. Administration of progesterone 12 h after estradiol prematurely reduced the level of Cx-43 transcripts. These data demonstrate that steroid hormones can modulate the level of steady state transcripts of Cx-43 during pregnancy in association with changes in uterine contractile activity. Furthermore, the data from the nonpregnant studies suggest that the levels of transcripts are regulated positively by estradiol and negatively by progesterone.