Immunoassay of human chorionic gonadotropin, its free subunits, and metabolites.

Multiple hCG-related molecules are present in pregnancy serum and urine samples. These include non-nicked hCG (the hormone), nicked hCG, hyper- and hypoglycosylated hCG, hCG missing the C-terminal extension, free alpha-subunit, large free alpha-subunit, free beta-subunit, nicked free beta-subunit, and beta-core fragment. Over 100 immunoassays are sold for quantifying hCG-related molecules in serum or urine. Each measures nonnicked hCG and one of seven combinations of the other hCG-related molecules. This is the source of interassay discordance in hCG determinations. Whereas minor variations are noted in different kit results in normal pregnancy samples (more than twofold variation), much larger variations may be found in two immunoassay results in irregular gestations (spontaneous abortion, aneuploidy, preeclampsia, cancers, and trophoblast disease). Care is needed in choosing an immunoassay. What the assay measures may be more important than its cost or speed. This article reviews the structure of hCG and related molecules. It examines the stability and degradation of hCG, and recognition of hCG-related molecules by different types of immunoassay. Also reviewed are new assays for specifically detecting these other hCG-related molecules.

[1]  N. Javadpour.  Current status of tumor markers in testicular cancer. A practical review. , 1992, European urology.

[2]  R. Berkowitz,et al.  Human Chorionic Gonadotropin and Free Subunits' Serum Levels in Patients With Partial and Complete Hydatidiform Moles , 1989, Obstetrics and gynecology.

[3]  R. Moncayo,et al.  Evidence for the presence of human chorionic gonadotropin (hCG) and free beta-subunit of hCG in the human pituitary. , 1990, The Journal of clinical endocrinology and metabolism.

[4]  M. Hazama,et al.  [Urinary hCG beta-core fragment as a tumor marker for bladder cancer]. , 1993, Nihon Hinyokika Gakkai zasshi. The japanese journal of urology.

[5]  U. Stenman,et al.  Pregnancy Serum Contains the β-Core Fragment of Human Choriogonadotropin , 1990 .

[6]  M. Okamura,et al.  [Assessment of urinary beta-core fragment of hCG as a tumor marker of cervical cancer]. , 1992, Nihon Sanka Fujinka Gakkai zasshi.

[7]  L. Cole,et al.  The heterogeneity of human chorionic gonadotropin (hCG). II. Characteristics and origins of nicks in hCG reference standards. , 1991, Endocrinology.

[8]  D. Bahner,et al.  The effect of thermal instability of intact human chorionic gonadotropin (ihcg) on the application of its free β‐subunit (free βhcg) as a serum marker in down syndrome screening , 1995, Prenatal diagnosis.

[9]  U. Stenman,et al.  Pregnancy serum contains the beta-core fragment of human choriogonadotropin. , 1990, The Journal of clinical endocrinology and metabolism.

[10]  S. Goto,et al.  Radioimmunoassay of the serum free beta-subunit of human chorionic gonadotropin in trophoblastic disease. , 1987, The Journal of clinical endocrinology and metabolism.

[11]  L. Cole,et al.  Selecting human chorionic gonadotropin immunoassays: consideration of cross-reacting molecules in first-trimester pregnancy serum and urine. , 1993, American journal of obstetrics and gynecology.

[12]  B. Nisula,et al.  Distribution, Metabolism, and Excretion of Human Chorionic Gonadotropin and Its Subunits in Man , 1980 .

[13]  L. Cole,et al.  The heterogeneity of human chorionic gonadotropin (hCG). III. The occurrence and biological and immunological activities of nicked hCG. , 1991, Endocrinology.

[14]  D. Krantz,et al.  Maternal serum Down syndrome screening: free beta-protein is a more effective marker than human chorionic gonadotropin. , 1990, American journal of obstetrics and gynecology.

[15]  L. Cole,et al.  Structure of the human chorionic gonadotropin beta-subunit fragment from pregnancy urine. , 1988, Endocrinology.

[16]  D. Bangham,et al.  International Reference Preparation of Human Chorionic Gonadotrophin for Immunoassay: potency estimates in various bioassay and protein binding assay systems; and International Reference Preparations of the alpha and beta subunits of human chorionic gonadotrophin for immunoassay. , 1980, The Journal of endocrinology.

[17]  L. Cole.  Stability of hCG free β‐subunit and β‐core fragment in urine , 1997 .

[18]  U. Stenman,et al.  Serum levels of human chorionic gonadotropin in nonpregnant women and men are modulated by gonadotropin-releasing hormone and sex steroids. , 1987, The Journal of clinical endocrinology and metabolism.

[19]  B. Nisula,et al.  Renal Metabolism of the β-Subunit of Human Choriogonadotropin in the Rat , 1986 .

[20]  L. Cole,et al.  Detecting and monitoring trophoblastic disease. New perspectives on measuring human chorionic gonadotropin levels. , 1994, The Journal of reproductive medicine.

[21]  L. Cole,et al.  β-Core Fragment (β-Core/UGF/UGP), a Tumor Marker: A 7-Year Report , 1996 .

[22]  J. Canick,et al.  Detection of β-core fragment in second trimester Down's syndrome pregnancies , 1996 .

[23]  D. Blithe,et al.  Variations in the oligosaccharides on free and combined alpha-subunits of human choriogonadotropin in pregnancy. , 1985, Endocrinology.

[24]  S. Birken,et al.  Isolation and characterization of human pituitary chorionic gonadotropin. , 1996, Endocrinology.

[25]  H. Cuckle,et al.  Urinary β‐core human chorionic gonadotrophin: A new approach to Down's syndrome screening , 1994, Prenatal diagnosis.

[26]  L. Cole,et al.  THE STABILITY OF hCG AND FREE β‐SUBUNIT IN SERUM SAMPLES , 1997 .

[27]  L. Cole,et al.  Human chorionic gonadotropin beta-subunit nicking enzymes in pregnancy and cancer patient serum. , 1994, The Journal of clinical endocrinology and metabolism.

[28]  K. Spencer,et al.  Dual Analyte Immunoassay in Neural Tube Defect and Down's Syndrome Screening: Results of a Multicentre Clinical Trial , 1993, Annals of clinical biochemistry.

[29]  J. Hobbins,et al.  Peptide heterogeneity of human chorionic gonadotropin hcg and its beta subunit in down syndrome pregnancies , 1992 .

[30]  L. Cole,et al.  The heterogeneity of human chorionic gonadotropin (hCG). I. Characterization of peptide heterogeneity in 13 individual preparations of hCG. , 1991, Endocrinology.

[31]  J. Bidart,et al.  Characterization of a cleavage product in the human choriogonadotropin β-subunit , 1988 .

[32]  D. Puett,et al.  The kinetic and equilibrium parameters of subunit association and gonadotropin dissociation. , 1982, The Journal of biological chemistry.

[33]  B. Nisula,et al.  Renal metabolism of the beta-subunit of human choriogonadotropin in the rat. , 1986, Endocrinology.

[34]  L. Cole,et al.  The deactivation of hCG by nicking and dissociation. , 1993, The Journal of clinical endocrinology and metabolism.

[35]  B. Malassagne,et al.  Free Human Chorionic Gonadotropin β Subunit in Gonadal and Nongonadal Neoplasms , 1992 .

[36]  W. Fitch,et al.  Primary structure of cholera toxin beta-chain: a glycoprotein hormone analog? , 1977, Science.

[37]  D. Seligson,et al.  Clinical Chemistry , 1965, Bulletin de la Societe de chimie biologique.

[38]  D. C. Harris,et al.  Crystal structure of human chorionic gonadotropin , 1994, Nature.

[39]  R. Osathanondh,et al.  Second‐trimester levels of maternal urinary gonadotropin peptide in down syndrome pregnancy , 1995, Prenatal diagnosis.

[40]  T. Maruo,et al.  Studies on the apparent human chorionic gonadotropin-like factor in the crab Ovalipes ocellatus. , 1979, Endocrinology.

[41]  R. Canfield,et al.  The amino acid sequence of human chorionic gonadotropin. The alpha subunit and beta subunit. , 1975, The Journal of biological chemistry.