Development of an assay for a biomarker of pregnancy and early fetal loss
Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodies that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with kinetic advantages derived from the concentration factors by use of the sandwich assay technique (immunoradiometric assay, IRMA), have enabled development of extremely sensitive and specific measurement protocols for urinary hCG. The assay described herein permits the detection of pregnancy on an average 25.4 days after the first day of the preceding menses, as opposed to 29.5 days for conventional radioimmunoassay techniques. In addition, the greater sensitivity and specificity of this assay method has permitted the detection of episodes of fetal loss not detected by radioimmunoassay of urine specimens. A large scale epidemiological study is in progress using this assay technique as a way to identify pregnancies that are lost before becoming clinically apparent.
- Research Organization:
- Columbia Univ., New York, NY (United States)
- OSTI ID:
- 5512817
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 74
- Country of Publication:
- United States
- Language:
- English
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HCG
AMINO ACID SEQUENCE
RADIOIMMUNOASSAY
PREGNANCY
BIOLOGICAL MARKERS
BIOCHEMISTRY
EPIDEMIOLOGY
FETUSES
IMMUNOLOGY
MONOCLONAL ANTIBODIES
ANTIBODIES
CHEMISTRY
GONADOTROPINS
HORMONES
IMMUNOASSAY
ISOTOPE APPLICATIONS
MOLECULAR STRUCTURE
PEPTIDE HORMONES
PITUITARY HORMONES
RADIOASSAY
RADIOIMMUNOLOGY
TRACER TECHNIQUES
550601* - Medicine- Unsealed Radionuclides in Diagnostics