Circulating LH/hCG receptor (LHCGR) may identify pre-treatment IVF patients at risk of OHSS and poor implantation

Chambers, A.; Nayini, Krishnaveni; Mills, Walter; Lockwood, Gillian; Banerjee, Subhasis

doi:10.1186/1477-7827-9-161

Cited by 13 publications

(11 citation statements)

References 46 publications

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“…The protein identified in the current study of around 75 kDa in serum from men with TGCTs may be representing the full-length receptor, while the lower molecular weight band (50 kDa) may represent a truncated or cleaved receptor protein. This suggestion is supported by showing similar band sizes in gonadal tissues and is in accordance with previous studies investigating LHCGR in serum [ 10 , 35 , 36 ]. We hypothesized that the circulating LHCGR or its fragment could have diagnostic potential in patients with TGCT.…”

Section: Discussionsupporting

confidence: 92%

“…Later, it was identified in the medium of ligand-induced rat and mouse Leydig cells [ 34 ] or human cells transfected with cloned LHCGR [ 18 , 35 ]. In humans, LHCGR has been found in serum and follicular fluid of women [ 10 ] and by proteomics in serum from men and women [ 36 ] but could it also be released from seminoma cells and be measured in serum? We have recently shown that different LHCGR fragments are released into serum of healthy men [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to full-length LHCGR, several truncated variants are produced by alternative splicing [ 9 ]. Some of these isoforms have been suggested to be secreted and LHCGR may also be cleaved off leading to a cell free soluble LHCGR that has been shown in serum and follicular fluid of women [ 10 ] and serum of men [ 11 ]. Several studies have suggested that LHCGR may be involved in the pathogenesis of endocrine related cancers—for instance breast [ 12 ], ovarian, and endometrial [ 13 ], adrenocortical [ 14 ], pancreatic [ 15 ] and prostate [ 16 ] cancer.…”

Section: Introductionmentioning

confidence: 99%

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Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis

Lorenzen

Nielsen

Andreassen

et al. 2020

Cancers

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Luteinizing hormone/choriogonadotropin receptor (LHCGR) regulates gonadal testosterone production and recent studies have suggested a growth-regulatory role in somatic cancers. Here, we established that LHCGR is expressed in a fraction of seminoma cells and germ cell neoplasia in situ (GCNIS), and the seminoma-derived cell line TCam2 released LHCGR into the medium. LH treatment induced proliferation of TCam2 cells in vitro, while hCG treatment induced a non-significant 51% increase in volume of tumors formed in a TCam2 xenograft model. A specific ELISA was used to detect a soluble LHCGR in serum. Serum concentrations of soluble LHCGR could not distinguish 4 patients with GCNIS and 216 patients with testicular germ cell tumors (TGCTs) from 297 infertile or 148 healthy young men. Instead, serum LHCGR levels were significantly higher in 112 patients with a seminoma >5 cm or elevated serum lactate dehydrogenase (LDH) compared with men harboring smaller seminomas <2 cm or normal LDH levels. Serum LHCGR levels in TGCT patients could not predict relapse irrespective whether determined pre- or post-orchiectomy. Combined, these novel findings suggest that LHCGR may be directly involved in the progression and growth of seminomas, and our retrospective pilot study suggests that serum LHCGR may have some prognostic value in men with seminoma.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis

Lorenzen

Nielsen

Andreassen

et al. 2020

Cancers

View full text Add to dashboard Cite

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“…Other laboratories had shown that the expression of soluble LHCGR (sLHCGR, N-terminal 336 residues of the extracellular domain) as a thioredoxin fusion protein in E . coli carrying mutations in both thioredoxin reductase ( TrxB ) and glutathione reductase ( gor ) genes [14], had a similar specificity and affinity for hCG as the intact native LHCGR [15]. Therefore, this protocol was followed in order to produce the sLHCGR standard calibrator for ELISA assays.…”

Section: Methodsmentioning

confidence: 99%

Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia

Chambers

Griffin

Naif

et al. 2012

Reprod Biol Endocrinol

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BackgroundSoluble LH/hCG receptor (sLHCGR) released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex.MethodsAnti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy.ResultsTwo ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down’s syndrome (DS), preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL), and high (equal to or greater than 170 pmol/mL) concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21%) which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth) exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL) compared to controls (median 16.15 pmol/mL, n = 390). The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL) in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR.ConclusionsSerum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy.

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“…In fact, hCG has been shown to specifically upregulate MMP-2 and MMP-9 [ 11 , 12 ] and several studies have shown post-transcriptional regulation of LHCGR [ 13 , 14 ]. Soluble LHCGR (sLHCGR) has been measured by an ELISA platform in both serum and follicular fluid from women [ 15 , 16 ]. The specificity of the antibodies used in the ELISA assay were validated by expressing different LHCGR fragments in CHO cells for epitope mapping and by examining expression in the human placenta [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Possible Relevance of Soluble Luteinizing Hormone Receptor during Development and Adulthood in Boys and Men

Mortensen

Lorenzen

Jørgensen

et al. 2021

Cancers

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Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are agonists for the luteinizing hormone receptor (LHCGR) which regulates male reproductive function. LHCGR may be released into body fluids. We wish to determine whether soluble LHCGR is a marker for gonadal function. Cross-sectional, longitudinal, and intervention studies on 195 healthy boys and men and 396 men with infertility, anorchia, or Klinefelter Syndrome (KS) were used to correlate LHCGR measured in serum, seminal fluid, urine, and hepatic/renal artery and vein with gonadal function. LHCGR was determined in fluids from in vitro and in vivo models of human testicular tissue and cell lines, xenograft mouse models, and human fetal kidney and adrenal glands. Western blot showed LHCGR fragments in serum and gonadal tissue of similar size using three different antibodies. The LHCGR-ELISA had no species cross-reactivity or unspecific reaction in mouse serum even after human xenografting. Instead, sLHCGR was released into the media after the culture of a human fetal kidney and adrenal glands. Serum sLHCGR decreased markedly during puberty in healthy boys (p = 0.0001). In healthy men, serum sLHCGR was inversely associated with the Inhibin B/FSH ratio (β −0.004, p = 0.027). In infertile men, seminal fluid sLHCGR was inversely associated with serum FSH (β 0.006, p = 0.009), sperm concentration (β −3.5, p = 0.003) and total sperm count (β −3.2, p = 0.007). The injection of hCG lowered sLHCGR in serum and urine of healthy men (p < 0.01). In conclusion, sLHCGR is released into body-fluids and linked with pubertal development and gonadal function. Circulating sLHCGR in anorchid men suggests that sLHCGR in serum may originate from and possibly exert actions in non-gonadal tissues. (ClinicalTrials: NTC01411527, NCT01304927, NCT03418896).

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Circulating LH/hCG receptor (LHCGR) may identify pre-treatment IVF patients at risk of OHSS and poor implantation

Cited by 13 publications

References 46 publications

Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis

Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis

Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia

Possible Relevance of Soluble Luteinizing Hormone Receptor during Development and Adulthood in Boys and Men

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