Prostaglandins and mechanisms of preterm birth.
Prostaglandins and mechanisms of preterm birth.
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DOI：
10.1530/rep.0.1240001
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发表时间：
2002-07
期刊：
影响因子：
3.8
通讯作者：
J. Challis;D. Sloboda;N. Alfaidy;S. Lye;W. Gibb;F. Patel;W. Whittle;J. Newnham
中科院分区：
文献类型：
--
作者：
J. Challis;D. Sloboda;N. Alfaidy;S. Lye;W. Gibb;F. Patel;W. Whittle;J. Newnham
足月和早产时子宫收缩力的增加首先是由于子宫肌层的激活，然后是刺激。子宫的机械牵拉和胎儿下丘脑-垂体-肾上腺轴活动增加引起的内分泌途径可引起激活。在绵羊胎儿中，妊娠期间皮质醇分泌增加以雌激素非依赖性方式调节胎盘中前列腺素合成酶2型（PGHS-2）的表达，导致胎儿循环中前列腺素E2（PGE2）浓度增加。随后，母体子宫PGHS-2表达的增加需要雌激素的增加，并导致母体循环中PGF（2 α）浓度的增加。因此，PGHS-2在足月时的调节在胎儿（滋养层）和母体（子宫上皮）组织中受到不同的控制。这种差异可能反映了胎盘滋养层细胞糖皮质激素受体的表达，而不是雌激素受体（ER）的表达。在女性中，皮质醇还通过上调PGHS-2（羊膜和绒毛膜）和下调15-OH前列腺素脱氢酶（PGDH;绒毛膜滋养层）来增加胎儿组织中的前列腺素产生。皮质醇对绒毛膜中PGDH表达的影响可能通过旁分泌或自分泌作用逆转孕酮的紧张性刺激作用。在膜中，皮质醇可能通过11 β-羟基类固醇脱氢酶（11 β-HSD）1型的活性从可的松中衍生出来，除了从母体或胎儿肾上腺分泌。在胎盘中，11 β-HSD-2氧化酶活性占主导地位，低氧血症和先兆子痫妊娠的胎盘中该酶的表达减少。在这种情况下，母体皮质醇浓度的增加可能会进入胎儿室，导致生长受限和编程以后的生活疾病。
Increased uterine contractility at term and preterm results first from activation and then stimulation of the myometrium. Activation can be provoked by mechanical stretch of the uterus, and by an endocrine pathway resulting from increased activity of the fetal hypothalamic-pituitary-adrenal axis. In sheep fetuses, increased cortisol output during pregnancy regulates expression of prostaglandin synthase type 2 (PGHS-2) in the placenta in an oestrogen-independent manner, resulting in increased concentrations of prostaglandin E2 (PGE2) in the fetal circulation. Later increases in maternal uterine expression of PGHS-2 require increases in oestrogen and lead to increased concentrations of PGF(2alpha) in the maternal circulation. Thus, regulation of PGHS-2 at term is differentially controlled in fetal (trophoblast) and maternal (uterine epithelium) tissue. This difference may reflect expression of glucocorticoid receptor but not oestrogen receptor (ER) in placental trophoblast cells. In women, cortisol also contributes to increased prostaglandin production in fetal tissues through upregulation of PGHS-2 (amnion and chorion) and downregulation of 15-OH prostaglandin dehydrogenase (PGDH; chorion trophoblasts). The effect of cortisol on expression of PGDH in the chorion reverses a tonic stimulatory effect of progesterone, potentially through a paracrine or autocrine action. In membranes, cortisol may be derived from cortisone through activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1, in addition to secretion from the maternal or fetal adrenal glands. In placenta, 11beta-HSD-2 oxidase activity predominates and expression of this enzyme is reduced with hypoxaemia and in placentae from pre-eclamptic pregnancies. In these circumstances, increased concentrations of maternal cortisol may cross into the fetal compartment, contributing to growth restriction and programming later life disease.