LH/hCG receptor–independent activities of hCG and hCGβ

Koistinen, Hannu; Stenman, Ulf‐Hǎkan

doi:10.1016/b978-0-12-820050-6.00023-0

Cited by 3 publications

(4 citation statements)

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“…Since an increased protein expression of hCGβ has also been observed in tumor tissue, including extrahepatic CCA [19], it is likely that the associations with poor prognosis reflect the increased expression of hCGβ in malignant tissue. While it remains to be studied, it is plausible that hCGβ has a cancer-promoting role in CCA similar to that in other cancers [13], which would explain the increase in hCGβ levels observed before the diagnosis of CCA.…”

Section: Discussionmentioning

confidence: 99%

“…However, many nontrophoblastic tumors, such as those in various gastrointestinal tract tissues, produce free hCGβ, but very rarely intact hCG [10]. For hCGβ, several, likely LHCGR-independent, cancer progression-relevant functions have been described, including the promotion of cell migration and invasion, which are associated with epithelial-to-mesenchymal transition-like changes in the cells [13]. This is in line with studies showing that serum levels of hCGβ are strongly associated with adverse prognosis in many nontrophoblastic cancers [10].…”

Section: Introductionmentioning

confidence: 99%

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Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Koistinen

Boyd

Arola

et al. 2021

Livers

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Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease, which is associated with an increased risk of cholangiocarcinoma (CCA). Novel markers, to complement or replace CA19-9, are urgently needed for the screening of PSC-associated biliary neoplasia. Previous studies have suggested that serum trypsinogen-2 and human chorionic gonadotropin β-subunit (hCGβ) may serve as such markers. Using highly specific in-house immunoassays, we studied trypsin(ogen)-2 and -3, SPINK1 and hCGβ in bile samples of 214 patients, referred for endoscopic retrograde cholangiography. We found that biliary trypsinogen-2 was decreased (p = 0.027) and hCGβ was elevated (p < 0.001) in PSC patients who were diagnosed 1.6 years (median, range 0.1–8.8 years) later with CCA or in whom biliary dysplasia was observed at least twice in brush cytology (n = 11) as compared to PSC patients without CCA or repeated dysplasia (n = 171). The other studied markers did not show significant differences between these groups. Our results warrant further evaluation of hCGβ as a predictive marker for PSC-associated biliary neoplasia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Koistinen

Boyd

Arola

et al. 2021

Livers

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“…Unconventional, paracrine actions of hCG have been reported for more than twenty years and were recently reviewed ( 63 , 135 – 137 ) and only effects that are not suspected to be dependent on a LH-CGR activation or to result from possible contaminants present in the preparations used will be mentioned below.…”

Section: Unconventional Actions Of Gphs or Their Subunitsmentioning

confidence: 99%

Unconventional Actions of Glycoprotein Hormone Subunits: A Comprehensive Review

Quérat

2021

Front. Endocrinol.

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The glycoprotein hormones (GPH) are heterodimers composed of a common α subunit and a specific β subunit. They act by activating specific leucine-rich repeat G protein-coupled receptors. However, individual subunits have been shown to elicit responses in cells devoid of the receptor for the dimeric hormones. The α subunit is involved in prolactin production from different tissues. The human chorionic gonadotropin β subunit (βhCG) plays determinant roles in placentation and in cancer development and metastasis. A truncated form of the thyrotropin (TSH) β subunit is also reported to have biological effects. The GPH α- and β subunits are derived from precursor genes (gpa and gpb, respectively), which are expressed in most invertebrate species and are still represented in vertebrates as GPH subunit paralogs (gpa2 and gpb5, respectively). No specific receptor has been found for the vertebrate GPA2 and GPB5 even if their heterodimeric form is able to activate the TSH receptor in mammals. Interestingly, GPA and GPB are phylogenetically and structurally related to cysteine-knot growth factors (CKGF) and particularly to a group of antagonists that act independently on any receptor. This review article summarizes the observed actions of individual GPH subunits and presents the current hypotheses of how these actions might be induced. New approaches are also proposed in light of the evolutionary relatedness with antagonists of the CKGF family of proteins.

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“… 37 hCG is used to detect pregnancy at a very early stage and plays an important role in pregnancy maintenance because it supports luteal progesterone production by activating the LH/hCG receptor (LHCGR). 37 Several other critical roles, that may be independent of LHCGR, 38 , 39 have been proposed. 40 – 43 There are four forms of hCG, including the intact hormone (intact hCG, which is a heterodimer of alpha- and beta-subunits), free

subunit (

), free

subunit (

), and hyperglycosylated intact hCG (h-hCG).…”

Section: Introductionmentioning

confidence: 99%

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York

Liang,

Koistinen,

Barrett

et al. 2024

Environ Health Perspect

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Background: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. Objectives: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-( ) and beta-subunits ( ), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. Methods: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. Results: Perfluorohexane sulfonic acid (PFHxS) [ : 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: ; 95% CI: , ) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with and positively with . Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with only in Black participants ( ; 95% CI: , ) and in participants with high school education or less ( ; 95% CI: , ); conversely, perfluorononanoic acid (PFNA) was negatively associated with only in White participants ( ; 95% CI: , ) and with only in participants with a college education or greater ( ; 95% CI: , ). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was . Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with , and PFNA with h-hCG. Conclusions: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with and differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biologic...

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LH/hCG receptor–independent activities of hCG and hCGβ

Cited by 3 publications

References 49 publications

Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Unconventional Actions of Glycoprotein Hormone Subunits: A Comprehensive Review

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York

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