A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies

<p>Abstract</p> <p>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 gesta...

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Main Authors: Spencer Kevin, Loosfelt Hugues, Papageorghiou Aris, Chambers Anne E, Smallwood Alan, Banerjee Subhasis, Campbell Stuart, Nicolaides Kypros
Format: Article
Language:English
Published: BMC 2005-06-01
Series:Reproductive Biology and Endocrinology
Online Access:http://www.rbej.com/content/3/1/25
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author Spencer Kevin
Loosfelt Hugues
Papageorghiou Aris
Chambers Anne E
Smallwood Alan
Banerjee Subhasis
Campbell Stuart
Nicolaides Kypros
author_facet Spencer Kevin
Loosfelt Hugues
Papageorghiou Aris
Chambers Anne E
Smallwood Alan
Banerjee Subhasis
Campbell Stuart
Nicolaides Kypros
author_sort Spencer Kevin
collection DOAJ
description <p>Abstract</p> <p>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 <it>CGB</it> (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 <it>(CGB)</it> RNA, <it>LHCGR</it> RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta <it>(CGB)</it> mRNA directly correlates with high serum hCG levels. The steady-state synthesis of <it>LHCGR</it> mRNA (exons 1–5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length <it>LHCGR</it> 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.</p>
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spelling doaj.art-d94e56637b9d465895b125d11ac8d1022022-12-22T03:26:00ZengBMCReproductive Biology and Endocrinology1477-78272005-06-01312510.1186/1477-7827-3-25A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnanciesSpencer KevinLoosfelt HuguesPapageorghiou ArisChambers Anne ESmallwood AlanBanerjee SubhasisCampbell StuartNicolaides Kypros<p>Abstract</p> <p>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 <it>CGB</it> (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 <it>(CGB)</it> RNA, <it>LHCGR</it> RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta <it>(CGB)</it> mRNA directly correlates with high serum hCG levels. The steady-state synthesis of <it>LHCGR</it> mRNA (exons 1–5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length <it>LHCGR</it> 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.</p>http://www.rbej.com/content/3/1/25
spellingShingle Spencer Kevin
Loosfelt Hugues
Papageorghiou Aris
Chambers Anne E
Smallwood Alan
Banerjee Subhasis
Campbell Stuart
Nicolaides Kypros
A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
Reproductive Biology and Endocrinology
title A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
title_full A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
title_fullStr A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
title_full_unstemmed A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
title_short A link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor (LHCGR) in Down's syndrome pregnancies
title_sort link between high serum levels of human chorionic gonadotrophin and chorionic expression of its mature functional receptor lhcgr in down s syndrome pregnancies
url http://www.rbej.com/content/3/1/25
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