Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure.
Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure.
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DOI：
10.1371/journal.pone.0148226
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Clifton VL
中科院分区：
文献类型：
--
作者：
Saif Z;Dyson RM;Palliser HK;Wright IM;Lu N;Clifton VL
胎盘糖皮质激素受体 (GR) 是糖皮质激素信号传导的核心，并介导类固醇对胎儿生长和肺成熟相关途径的影响，但尚未在豚鼠胎盘中检查 GR，尽管这种动物经常用作早产和过量糖皮质激素暴露的模型。豚鼠母鼠在早产或足月剖腹产前 24 小时和 12 小时皮下注射赋形剂或倍他米松。记录分娩时幼崽和器官的重量。解剖、称重并使用蛋白质印迹分析胎盘，以检查细胞核和细胞质提取物中 GR 亚型的表达。对豚鼠 GR 基因的比较检查发现，它能够产生 8 种翻译 GR 亚型中的 7 种，包括 GRα-A、C1、C2、C3、D1、D2 和 D3。豚鼠体内不产生 GRα-B。总 GR 抗体从足月 (n = 29) 和早产 (n = 27) 中识别出 10 个特定条带。已知的亚型包括 GRγ、GRα A、GRβ、GRP、GRA 和 GRα D1-3。胎盘GR亚型表达存在性别和孕龄差异。在所有组的细胞质中均检测到胎盘 GRα A，但在暴露于倍他米松的早产男性和女性以及未治疗的足月男性的细胞质和细胞核中显着增加（KW-ANOVA，P = 0.0001，P = 0.001）。暴露于倍他米松的女性早产胎盘以及早产和足月男性胎盘中 GRβ 的细胞质表达增加（P = 0.01）。在所有暴露于倍他米松的胎盘中，GRβ 的核表达均增加（P = 0.0001）。当暴露于倍他米松时，男性早产胎盘中 GRα D2 和 GRα D3 增加（P = 0.01，P = 0.02）。目前的数据表明，性别特异性胎盘对母体倍他米松的反应可能取决于 GR 亚型组合的表达。
The placental glucocorticoid receptor (GR) is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRα-A, C1, C2, C3, D1, D2, and D3. GRα-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29) and preterm pregnancies (n = 27). Known isoforms included GRγ, GRα A, GRβ, GRP, GRA and GRα D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRα A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001). Cytoplasmic expression of GRβ was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01). Nuclear expression of GRβ was increased in all placentae exposed to betamethasone (P = 0.0001). GRα D2 and GRα D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02). The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms.