Increased expression of connexin-43 in the rat myometrium during labor is associated with an increase in the plasma estrogen:progesterone ratio.

Abstract

The molecular mechanisms that regulate the synthesis of the myometrial gap junction protein, connexin-43 (Cx-43), are controversial. We measured myometrial Cx-43 messenger RNA, protein and gap junction frequency, and area in myometrial samples collected from nonpregnant rats and pregnant rats at days 5, 10, 15, 17, 18, 19, 20, 21, 22, 23 (during delivery), and 1 day postpartum and correlated these data with plasma concentrations of estradiol 17 beta and progesterone. Cx-43 transcripts were low or undetectable (connexin-43:glyceraldehyde phosphate dehydrogenase ratio < 0.2) in nonpregnant rats or in rats before day 10 of pregnancy. Transcripts rose to 0.52 +/- 0.11 on day 10, increased (2.9-fold) to 1.51 +/- 0.48 on day 22, and increased a further 2.9-fold to maximal levels of 4.42 +/- 0.67 during labor. Cx-43 protein was barely detectable on day 21 [0.12 +/- 0.04 relative optical density (ROD) units], increased 2.5-fold on day 22 (0.30 +/- 0.04 ROD units), and a further 3.7-fold during delivery (1.10 +/- 0.15 ROD units), at a time when gap junctions were present in large numbers in the cell membrane. Between day 21 and delivery the increase in Cx-43 transcripts (8.2-fold) and protein (9.2-fold) were of a similar magnitude. There was a significant positive correlation between the increases in Cx-43 transcripts and the increase in the ratio of plasma estradiol to progesterone. Levels of Cx-43 transcripts, protein, and gap junctions fell rapidly postpartum. Our data demonstrate: 1) that transcripts encoding the gap junction protein, Cx-43, are at maximal levels during delivery and that this increase is temporally associated with increases in Cx-43 protein and the appearance of gap junctions; and 2) that these data, in association with changes in plasma steroid concentrations, are consistent with myometrial Cx-43 transcript levels being regulated positively by estrogen and negatively by progesterone during pregnancy.

P2X receptors in the rat uterine cervix, lumbosacral dorsal root ganglia, and spinal cord during pregnancy

“…This pattern coincides temporally with a sharp rise in serum estrogen that begins at about 22 days of pregnancy (Lye et al 1993;Bridges 1984;Shaikh 1971). Given that many P2X 3 -receptor-positive neurons in L6-S1 DRG express ERs, the surge in estrogen could be a factor in the upregulation of these receptors, together with other neurochemicals important in parturition, e.g., substance P (SP) and calcitonin Mowa et al 2003a,b).…”

“…An explanation of the elevation of the protein at 2 days postpartum is not clear. However, if estrogen is a factor in P2X 3 -receptor expression, then P2X 3 protein levels may be maintained by this mechanism because serum estrogen levels remain elevated in the early postpartum period (Lye et al 1993;Bridges 1984;Shaikh 1971). On the other hand, inflammatory reactions can also alter the physiological properties of the P2X 3 -receptor-expressing DRG sensory neurons (increasing ATP-receptor currents) and promoting upregulation of the P2X 3 receptors (Xu and Huang 2002).…”

Sufficient Progesterone-Priming Prior to Estradiol Stimulation Is Required for Optimal Induction of the Cervical Prostaglandin System in Pregnant Sheep at 0.7 Gestations1

“…On the one hand, progesterone, acting as a gene suppressor, down-regulates a number of genes that are essential for myometrial contraction, including the gap junction protein [41,42], calcium channels, steroid receptor and associated proteins [40,43], and oxytocin receptor [41,44]. On the other hand, progesterone can also promote intrauterine PG production [23,29,30,45].…”

L’électromyogramme utérin : principes et intérêt pour le diagnostic de travail prématuré

“…En parallèle, il a été montré une augmentation de l'expression des protéines composant les gap-jonctions (connexines 43 essentiellement) également induite par la diminution de la progestérone [18,22]. Les mêmes changements ont été rapportés au cours du travail à terme et du travail prématuré.…”