Effects of 17β-estradiol on myometrial gap junctions and pregnancy in the rat

Abstract

The effects of estradiol treatment on the development of myometrial gap junctions and premature labour were investigated using timed pregnant rats. In control animals myometrial gap junctions were infrequent between days 17 and 20 of pregnancy, but began to develop on day 21 and were at maximum frequency, size, and membrane area on day 22 during delivery. Gap junctions were completely absent from the myometrium 48 h after delivery. Animals treated with 500 micrograms 17 beta-estradiol/day starting on day 16 of pregnancy developed numerous myometrial gap junctions and delivered their pups prematurely on day 19. Similarly, treatment with 50 micrograms estradiol/day resulted in the development of myometrial gap junctions on day 20 of pregnancy and premature labour. However, treatment with various doses of estradiol up to and including 500 micrograms/day for 3 days beginning 1 day before delivery was not able to maintain the presence of myometrial gap junctions during the postpartum period. These results support the hypothesis that estradiol stimulates the development of myometrial gap junctions and that the presence of gap junctions in the myometrium is a requirement for the occurrence of term, as well as preterm labour. Furthermore, it is evident from this study that the postpartum regression of myometrial gap junctions is not dependent on the decrease in estradiol.

Increased expression of estrogen receptor beta in human uterine smooth muscle at term

“…Estrogens are found to be stimulatory to the initiation of labor in animals that experience progesterone withdrawal before parturition (2)(3)(4). In contrast, in animals such as guinea pigs, which do not have pre-parturition progesterone withdrawal, estrogen is inhibitory to the initiation of labor (4).…”

Activation of Protein Kinase C in Human Uterine Smooth Muscle Induces connexin-43 Gene Transcription through an AP-1 Site in the Promoter Sequence

“…Progesterone suppresses cx43 gene transcription and inhibits the trafficking of Cx43 protein through the Golgi apparatus (12,16). Estrogen can induce premature cx43 expression and gap junction formation in the myometrium of pregnant animals (14,17). However, cx43 expression only remains high in estrogen-treated myometrial cells if internal uterine pressure is maintained after delivery (10).…”

Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats

“…For example, the treatment of timed-pregnant rats with mifepristone-induced uterine contractility , Doret et al 2005) that leads to delivery (Garfield et al 1987, Shi et al 2003, Doret et al 2005. In addition, we and others have shown that treatment with mifepristone caused an increase in contraction-associated proteins such as CX 43 (Mackenzie & Garfield 1986, Garfield et al 1987, Miyoshi et al 1996 and the OTR (Fang et al 1997) in the myometrium. Finally, delivery induced by mifepristone was shown to occur in a more narrow range of time when compared with the time frame for delivery from spontaneous labor at term (Li et al 2004).…”

“…We propose that COMT activity may help to mediate estrogen-related functions in the myometrium during pregnancy at term. These functions include increases in the levels of factors associated with contractility, such as CX 43 (Mackenzie & Garfield 1986, Verhoeff et al 1986, Oltra et al 2003, oxytocin (Fang et al 1996), and the receptors for oxytocin (Fang et al 1996) or PGs (Dong & Yallampalli 2000). Therefore, treatment with the COMT inhibitor may cause a reduction in one or more of these factors, which in turn could result in the attenuation of uterine contractility induced by mifepristone.…”

“…At term pregnancy, estrogen helps alter the biochemical and electrical properties of the myometrium by increasing levels of the proteins that are directly or indirectly involved in muscle contraction such as CX 43 (Mackenzie & Garfield 1986, Oltra et al 2003, and the a1 and b (b1) subunits of the L-type voltagedependent calcium channel (Tezuka et al 1995). In addition, estrogen may facilitate myometrial contractility by increasing the expression levels of oxytocin receptor (OTR; Fuchs et al 1983, Larcher et al 1995, Fang et al 1996 and the FP receptor that binds PGF2a (Dong & Yallampalli 2000).…”