A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
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DOI：
10.1186/1477-7827-3-25
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发表时间：
2005-06-21
影响因子：
4.4
通讯作者：
Nicolaides, K
中科院分区：
文献类型：
--
作者：
Banerjee, S;Smallwood, A;Nicolaides, K
人绒毛膜促性腺激素（hCG）从胎盘滋养层细胞释放，并通过维持黄体分泌孕酮参与建立妊娠。妊娠前2 - 3周内在母体循环中检测到血清hCG，并在妊娠前三个月结束时达到峰值，然后下降。在唐氏综合征（DS）妊娠，血清hCG仍然显着高于孕龄匹配的未受损妊娠。已经提出，血清hCG水平升高可能是由于CGB（hCG β）基因的转录过度激活，或糖基化hCG激素的半衰期增加，或两者兼而有之。另一种可能性是血清hCG水平仍然很高，这是由于激素的同源受体LHCGR的可用性降低，导致缺乏激素利用。我们通过定量绒毛膜绒毛样本中hCG β（CGB）RNA、LHCGR RNA和LHCGR蛋白的表达来验证这一假设。我们证明绒毛膜hCG β（CGB）mRNA的表达与高血清hCG水平直接相关。DS妊娠中LHCGRmRNA（外显子1 - 5）的稳态合成显著高于对照，但DS中全长LHCGRmRNA（外显子1 - 11）的表达与未受损妊娠相当。然而，高分子量成熟LHCGR蛋白的合成显着减少DS相比，未受损的妊娠，表明缺乏利用循环hCG在DS妊娠。
Human chorionic gonadotrophin (hCG) is released from placental trophoblasts and is involved in establishing pregnancy by maintaining progesterone secretion from the corpus luteum. Serum hCG is detected in the maternal circulation within the first 2 - 3 wks of gestation and peaks at the end of the first trimester before declining. In Down's syndrome (DS) pregnancies, serum hCG remains significantly high compared to gestation age-matched uncompromised pregnancies. It has been proposed that increased serum hCG levels could be due to transcriptional hyper-activation of the CGB ( hCG beta) gene, or an increased half life of glycosylated hCG hormone, or both. Another possibility is that serum hCG levels remain high due to reduced availability of the hormone's cognate receptor, LHCGR, leading to lack of hormone utilization. We have tested this hypothesis by quantifying the expression of the hCG beta ( CGB) RNA, LHCGR RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta ( CGB) mRNA directly correlates with high serum hCG levels. The steady- state synthesis of LHCGR mRNA (exons 1 - 5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length LHCGR mRNA ( exons 1 - 11) in DS was comparable to that of uncompromised pregnancies. However, the synthesis of high molecular weight mature LHCGR proteins was significantly reduced in DS compared to uncompromised pregnancies, suggesting a lack of utilization of circulating hCG in DS pregnancies.