Orsino A, Taylor C V, Lye S J
Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Endocrinology. 1996 May;137(5):1545-53. doi: 10.1210/endo.137.5.8612484.
Gap junctions are characteristically increased in the myometrium during term and preterm delivery and are thought to be essential for the development of labor contractions. The expression of connexin-43 (Cx-43), the major myometrial gap junction protein, is increased during delivery (associated with an increase in the plasma estradiol/progesterone ratio) and after estradiol treatment of ovariectomized nonpregnant rats. However, Cx-43 is only 1 member of at least 16 proteins encoded by this family of gap junction genes. Using a RT-PCR method, we identified the presence of another member of this family, Cx-26, in laboring rat myometrium. The temporal expression pattern of Cx-26 was assessed using Northern and Western analyses. In contrast to Cx-43, whose expression is low throughout the pregnancy but increases immediately before the onset of labor (day 23), the expression of Cx-26 increased on day 17, reached maximal levels between days 19-21, and fell to low levels before the onset of labor. Treatment of pregnant rats with progesterone beginning on day 20 (which blocks both the increase in Cx-43 expression and the onset of labor) maintained the elevated expression of Cx-26. Induction of preterm labor in rats after ovariectomy on day 17 inhibited the normal preterm increase in Cx-26 transcripts. Progesterone treatment of these animals reversed the effects of ovariectomy. Immunofluorescence data identified Cx-26 antigen in the cell membranes of myometrial cells and in the luminal and glandular epithelium of the endometrium in the late pregnant (day 21) uterus. These data suggest that the role of gap junction formation in the myometrium in relation to the maintenance of pregnancy and the onset of labor is much more complex than previously recognized. Myometrial cell-cell communication is afforded by at least two different gap junction proteins, Cx-43 and Cx-26, that not only exhibit temporally distinct patterns of expression but are also subject to differential regulation.
在足月分娩和早产期间，子宫肌层中的缝隙连接显著增加，被认为是分娩宫缩发展所必需的。连接蛋白43（Cx-43）是子宫肌层主要的缝隙连接蛋白，其表达在分娩期间（与血浆雌二醇/孕酮比值增加相关）以及对去卵巢未孕大鼠进行雌二醇治疗后会增加。然而，Cx-43只是这个缝隙连接基因家族编码的至少16种蛋白质中的一员。我们使用逆转录聚合酶链反应（RT-PCR）方法，在分娩大鼠的子宫肌层中鉴定出该家族的另一个成员Cx-26。使用Northern和Western分析评估了Cx-26的时间表达模式。与Cx-43不同，Cx-43在整个孕期表达较低，但在分娩开始前（第23天）立即增加，而Cx-26的表达在第17天增加，在第19 - 21天达到最高水平，并在分娩开始前降至低水平。从第20天开始用孕酮治疗怀孕大鼠（这会阻止Cx-43表达的增加和分娩的开始）可维持Cx-26的高表达。在第17天对大鼠进行卵巢切除术后诱导早产会抑制Cx-26转录本正常的早产增加。对这些动物进行孕酮治疗可逆转卵巢切除的影响。免疫荧光数据在妊娠晚期（第21天）子宫的子宫肌层细胞膜以及子宫内膜的腔上皮和腺上皮中鉴定出Cx-26抗原。这些数据表明，子宫肌层中缝隙连接形成在维持妊娠和分娩开始方面的作用比以前认识的要复杂得多。子宫肌层细胞间通讯由至少两种不同的缝隙连接蛋白Cx-43和Cx-26提供，它们不仅表现出时间上不同的表达模式，而且还受到不同的调节。
