Cross-Reaction with Luteinizing Hormone β-Core Is Responsible for the Age-dependent Increase of Immunoreactive β-Core Fragment of Human Chorionic Gonadotropin in Women with Nonmalignant Conditions

Abstract

AbstractBackground: The β-core fragment of human chorionic gonadotropin (hCGβcf), also termed “β-core” and urinary gonadotropin peptide (UGP), has been reported to be present in the urine of healthy women and to increase in concentration after menopause. This could reflect cross-reaction with the equivalent metabolite of luteinizing hormone (LH), the β-LH-core.Methods: We measured immunoreactive LH, hCG, free α-subunit, and free β-subunit hCG (hCGβ), as well as β-core, using the S504 RIA and Triton UGP enzyme immunoassay in 274 urine samples from women with nonmalignant gynecological conditions. The molar cross-reaction of each assay with purified β-LH-core was determined.Results: Cross-reaction with β-LH-core was 100% in the LH and the S504 β-core assay, 5% in the Triton UGP assay, and <0.1% in the hCG, free α-subunit, and free hCGβ assays. Median urine concentrations of all analytes showed an age-dependent increase. LH and free α-subunit concentrations were ∼103 pmol/mol creatinine; hCG and S504 β-core were ∼102 pmol/mol creatinine; free hCGβ and Triton UGP β-core were in the tens of pmol/mol creatinine. The S504 β-core concentrations were 10% of those of LH. S504 β-core was strongly correlated with LH, but not with hCG or with free hCGβ (LH, r2 = 0.45; hCG, r2 = 0.26; free hCGβ, r2 = 0.03). The concentrations of β-core detected by the Triton UGP assay, which has a 5% cross-reaction with β-LH-core, were 2% of LH and 5% of the S504 β-core concentrations. Triton UGP values correlated strongly with LH concentrations, but less well with S504 β-core, intact hCG, and free hCGβ (LH, r2 = 0.44; S504 β-core, r2 = 0.33; hCG, r2 = 0.32; free hCGβ, r2 = 0.19).Conclusions: Immunoreactive β-core in women free of malignancies reflects cross-reaction with concentrations of the metabolite of LH, β-LH-core, within the health-related reference interval.