University of Oulu

Hannu Koistinen, Mariann Koel, Maire Peters, Ago Rinken, Karolina Lundin, Timo Tuuri, Juha S. Tapanainen, Henrik Alfthan, Andres Salumets, Ulf-Håkan Stenman, Darja Lavogina, Hyperglycosylated hCG activates LH/hCG-receptor with lower activity than hCG, Molecular and Cellular Endocrinology, Volume 479, 2019, Pages 103-109, ISSN 0303-7207, https://doi.org/10.1016/j.mce.2018.09.006

Hyperglycosylated hCG activates LH/hCG-receptor with lower activity than hCG

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Author: Koistinen, Hannu1; Koel, Mariann2,3; Peters, Maire2,4;
Organizations: 1Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Competence Centre on Health Technologies, Tartu, Estonia
3Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
4Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
5Institute of Chemistry, University of Tartu, Tartu, Estonia
6Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
7Department of Obstetrics and Gynecology, University Hospital of Oulu, University of Oulu, Medical Research Center Oulu and PEDEGO Research Unit, Oulu, Finland
8Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021111755793
Language: English
Published: Elsevier, 2019
Publish Date: 2021-11-17
Description:

Abstract

While human chorionic gonadotropin (hCG) appears to have an essential role in early pregnancy, it is controversial whether the hyperglycosylated form of hCG (hCG-h), which is the major hCG isoform during the first 4–5 weeks of pregnancy, is able to activate LH/hCG receptor (LHCGR). To address this, we utilized different extensively characterized hCG and hCGβ reference reagents, cell culture- and urine-derived hCG-h preparations, and an in vitro reporter system for LHCGR activation. The WHO hCG reference reagent (99/688) was found to activate LHCGR with an EC50-value of 3.3 ± 0.6 pmol/L (n = 9). All three studied hCG-h preparations were also able to activate LHCGR, but with a lower potency (EC50-values between 7.1 ± 0.5 and 14 ± 3 pmol/L, n = 5–11, for all P < 0.05 as compared to the hCG reference). The activities of commercial urinary hCG (Pregnyl) and recombinant hCG (Ovitrelle) preparations were intermediate between those of the hCG reference and the hCG-h. These results strongly suggest that the hCG-h is functionally similar to hCG, although it has lower potency for LHCGR activation. Whether this explains the reduced proportion of hCG-h to hCG reported in patients developing early onset pre-eclampsia or those having early pregnancy loss remains to be determined.

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Series: Molecular and cellular endocrinology
ISSN: 0303-7207
ISSN-E: 0303-7207
ISSN-L: 0303-7207
Volume: 479
Pages: 103 - 109
DOI: 10.1016/j.mce.2018.09.006
OADOI: https://oadoi.org/10.1016/j.mce.2018.09.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
3121 General medicine, internal medicine and other clinical medicine
Subjects:
hCG
Funding: This work was supported by the Finnish Cancer Foundation; Sigrid Jusélius Foundation; the Finnish Society of Clinical Chemistry; the Estonian Ministry of Education and Research (IUT34-16 and IUT20-17); Enterprise Estonia (EU48695); the Horizon 2020 innovation program (WIDENLIFE, 692065); European Union FP7 Marie Curie Industry-Academia Partnerships and Pathways funding (IAPP, SARM, EU324509); and the MSCA-RISE-2015 project MOMENDO (691058).
Copyright information: © 2018 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
  https://creativecommons.org/licenses/by-nc-nd/4.0/