Division of Reproductive Endocrinology and Infertility, Department of Ob, Gyn and Women's Health, University of Louisville, Health Sciences Center, Louisville, KY 40292, USA.
Placenta. 2010 Jul;31(7):581-8. doi: 10.1016/j.placenta.2010.04.002. Epub 2010 Apr 24.
Whether the placenta contributes to some of the abnormal hormonal profiles in gestational diabetes mellitus (GDM) pregnancies and whether GDM affects placental endocrine signaling pathways are yet to be established. The objective of this study was to investigate differences in the expression of the placental steroid and peptide hormone synthesis-related factors, enzymes and their receptors between normal and GDM pregnancies. Nine term placentae from GDM pregnancies and twelve from healthy pregnancies were collected. The results of immunohistochemistry, Western blotting and semiquantitative RT-PCR indicated that mRNA and protein levels of leptin, leptin receptors, androgen receptor and FGF2 were significantly higher in the GDM placentae than non-GDM placentae; while NRIH3, NRIH2, StARD3, CYP11A1, HSD3B, HSD11B, HSD17B, ERalpha, ERbeta, progesterone receptor, FGF receptor-2, insulin receptor-alpha and -beta showed no differences. Interestingly, Western blotting and immunohistochemistry revealed that aromatase protein concentrations in the GDM placentae were significantly reduced without a change in mRNA levels. Moreover, androgen upregulated FGF2 expression in the placental villous explants. These findings suggest that the placentae of GDM pregnancies contribute to elevated testosterone and leptin levels due to a decrease in the conversion of testosterone to estrogens and to an increase in leptin production. The androgen and leptin signaling pathways may be over-activated by the presence of excessive ligands and overexpressed receptors in GDM placentae. Dysregulation of these two endocrine networks may contribute to placental abnormalities eventually increasing the frequency of maternal and fetal complications associated with GDM.
胎盘是否会导致妊娠期糖尿病(GDM)妊娠中的一些异常激素谱,以及 GDM 是否会影响胎盘内分泌信号通路,目前尚不清楚。本研究旨在探讨正常妊娠和 GDM 妊娠胎盘类固醇和肽类激素合成相关因子、酶及其受体表达的差异。收集了 9 例 GDM 妊娠和 12 例正常妊娠的足月胎盘。免疫组织化学、Western blot 和半定量 RT-PCR 的结果表明,GDM 胎盘中瘦素、瘦素受体、雄激素受体和 FGF2 的 mRNA 和蛋白水平明显高于非 GDM 胎盘;而 NRIH3、NRIH2、StARD3、CYP11A1、HSD3B、HSD11B、HSD17B、ERalpha、ERbeta、孕激素受体、FGF 受体-2、胰岛素受体-α和 -β 则无差异。有趣的是,Western blot 和免疫组织化学显示,GDM 胎盘中的芳香酶蛋白浓度明显降低,而 mRNA 水平没有变化。此外,雄激素上调了胎盘绒毛外植体中 FGF2 的表达。这些发现表明,由于 GDM 胎盘中转氨酶向雌激素的转化减少以及瘦素产生增加,GDM 妊娠的胎盘会导致睾酮和瘦素水平升高。在 GDM 胎盘中,过多的配体和过度表达的受体可能使雄激素和瘦素信号通路过度激活。这两个内分泌网络的失调可能导致胎盘异常,最终增加与 GDM 相关的母体和胎儿并发症的发生频率。
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