Document Detail


Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy.
MedLine Citation:
PMID:  14764788     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Total human chorionic gonadotropin (hCG) is high in maternal serum at 14-18 wk of trisomy 21 (T21)-affected pregnancy, despite low placental hCG synthesis. We sought an explanation for this paradox. We first observed that, in T21-affected pregnancies, maternal serum hCG levels peaked at around 10 wk and then followed the same pattern throughout pregnancy as in controls, albeit at a higher (2.2-fold) level. After delivery, hCG clearance was not significantly different from that in controls. We isolated cytotrophoblasts from 29 T21-affected placentas (12-25 wk) and 13 gestational age-matched control placentas and cultured them for 3 d. In this large series, we confirmed that, in the culture medium of trophoblasts isolated from T21 placentas, hCG secretion was significantly lower (P < 0.003) than in controls, in contrast to the high hCG in maternal serum of the same patients. In T21 cultured trophoblasts, transcripts of sialyltransferase-1 and fucosyltransferase-1 were abnormally high. In corresponding culture medium, hCG was abnormally glycosylated; highly acidic [isoelectric points (pHi) = 4.5] as shown by isoelectric focusing, immunoblotting, and lectin binding; and weakly bioactive (46% of control) as determined using the Leydig cell model. In conclusion, T21 trophoblast cells produced hCG that was weakly bioactive and abnormally glycosylated but whose maternal clearance was unaltered.
Authors:
J-L Frendo; J Guibourdenche; G Pidoux; M Vidaud; D Luton; Y Giovangrandi; D Porquet; F Muller; D Evain-Brion
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  89     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-06     Completed Date:  2004-03-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  727-32     Citation Subset:  AIM; IM    
Affiliation:
Institut National de la Santé et de la Recherche Médicale, U 427, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 75270 Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / genetics
Cells, Cultured
Chorionic Gonadotropin / administration & dosage,  biosynthesis*,  blood
Culture Media / chemistry,  pharmacology
Down Syndrome / metabolism*,  pathology
Female
Fucosyltransferases / genetics
Glycosylation
Humans
Leydig Cells / metabolism
Male
Pregnancy / blood,  metabolism*
Progesterone / antagonists & inhibitors,  secretion
RNA, Messenger / metabolism
Sialyltransferases
Trophoblasts / metabolism*,  pathology
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Chorionic Gonadotropin; 0/Culture Media; 0/RNA, Messenger; 57-83-0/Progesterone; EC 2.4.1.-/Fucosyltransferases; EC 2.4.1.69/galactoside 2-alpha-L-fucosyltransferase; EC 2.4.99.-/Sialyltransferases; EC 2.4.99.1/ST6GAL1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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