DOWN-REGULATION OF G-ALPHA(S) IN HUMAN MYOMETRIUM IN TERM AND PRETERM LABOR - A MECHANISM FOR PARTURITION

DOWN-REGULATION OF G-ALPHA(S) IN HUMAN MYOMETRIUM IN TERM AND PRETERM LABOR - A MECHANISM FOR PARTURITION
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DOI:
10.1210/jc.79.6.1835
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发表时间:
1994-12-01
影响因子:
5.8
通讯作者:
BERNAL, AL
BERNAL, AL
中科院分区:
医学2区
文献类型:
--
作者:
EUROPEFINNER, GN;PHANEUF, S;BERNAL, AL

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我们以前曾报道,妊娠妇女子宫肌层中G α的表达水平明显高于非妊娠妇女。在本研究中,我们已经确定腺苷酸环化酶的活性在子宫肌层膜测量转换[α-P-32]cAMP和鸟苷三磷酸结合蛋白的表达与特异性抗体的免疫印迹。在这里,我们报告说,妊娠子宫肌层中G alpha表达的增加与G alpha偶联腺苷酸环化酶活性的显着增加有关,这是通过在5 '-鸟苷酸-亚氨二磷酸存在和不存在的情况下孵育子宫肌膜来估计的。前列腺素E(2)。此外,在自然分娩妇女的子宫肌层中,G α(s)水平和G α(s)偶联腺苷酸环化酶活性降低至非妊娠组织中观察到的水平。在非妊娠、妊娠和分娩组织中,毛喉素刺激的腺苷酸环化酶活性没有明显变化。妊娠子宫肌层中G α表达的增加可能促进激动剂诱导的cAMP形成,导致妊娠期间子宫舒张时间延长。G α(s)的下调会降低cAMP的舒张作用,可能是分娩启动的触发机制。
We have previously reported that G alpha(s) is expressed at considerably higher levels in myometrium taken from pregnant than from nonpregnant women. In the present study we have determined adenylyl cyclase activity in myometrial membranes by measuring the conversion of [alpha-P-32 to [P-32]cAMP and have measured guanosine triphosphate-binding protein expression by immunoblotting with specific antibodies. Here we report that the increase in G alpha(s) expression in pregnant myometrium is associated with a significant increase in G alpha(s)-coupled adenylyl cyclase activity, as estimated by incubating myometrial membranes in the presence of 5'-guanylyl-imidodiphosphate with and without prostaglandin E(2). Moreover, in myometrium from women in spontaneous labor G alpha(s) levels and G alpha(s)-coupled adenylyl cyclase activity are reduced to the levels observed in nonpregnant tissue. There was no apparent change in forskolin-stimulated adenylyl cyclase activity in nonpregnant, pregnant, and laboring tissue. The increase in G alpha(s) expression in pregnant myometrium may facilitate agonist-induced cAMP formation, resulting in prolonged relaxation of the uterus during gestation. Down-regulation of G alpha(s) would decrease the relaxing effect exerted by cAMP and may be a triggering mechanism for the initiation of labor.