Hyperglycosylated hCG activates LH/hCG-receptor with lower activity than hCG
Koistinen, Hannu; Koel, Mariann; Peters, Maire; Rinken, Ago; Lundin, Karolina; Tuuri, Timo; Tapanainen, Juha S.; Alfthan, Henrik; Salumets, Andres; Stenman, Ulf-Håkan; Lavogina, Darja (2018-10-02)
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
© 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/
https://urn.fi/URN:NBN:fi-fe2021111755793
Tiivistelmä
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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