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Use of polyclonal and monoclonal antibodies to study hCG-receptor interactions

Thesis/Dissertation ·
OSTI ID:6655599
Although the glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) bind to different receptors, each contains an identical alpha subunit. Specificity is somehow endowed by theta subunits which are distinct for each hormone. Human choriogonadotropin (hCG) is a natural LH analog that contains a beta subunit nearly identical to that of LH. The roles of these subunits in the recognition and high affinity binding of hCG to receptor was examined. Polyclonal and monoclonal antibodies specific for the individual subunits of hCG were used to probe the hormone-receptor interaction. Conformation-specific and sequence-specific antibodies were examined for their abilities to bind Triton X-100-solubilized /sup 125/I-hCG-receptor complex and to inhibit hormone binding to crude rat ovarian membranes containing receptor. Even though the immunoreactive sites are not located on the receptor binding surface of the beta subunit, most, but not all, of these polyclonal and monoclonal antibodies were able to inhibit /sup 125/I-hCG binding to receptor. Although the inhibition of binding may be due to steric interference due to the size of the antibody molecules, a two-step model for hCG binding to receptor is presented that also explains these results. In this model, the beta subunit initially binds with the receptor with a highly specific but low affinity interaction. This activates a site for the high affinity binding of the alpha subunit and stabilization of the complex. This is an attractive model as it may be applied to other glycoprotein hormones sharing an alpha subunit.
Research Organization:
Michigan Univ., Ann Arbor (USA)
OSTI ID:
6655599
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CELL CONSTITUENTS
CELL MEMBRANES
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
FEMALE GENITALS
FSH
GLUCOPROTEINS
GONADOTROPINS
GONADS
HCG
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LH
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MOLECULAR STRUCTURE
MONOCLONAL ANTIBODIES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
OVARIES
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RATS
RECEPTORS
RODENTS
SACCHARIDES
TRACER TECHNIQUES
TSH
VERTEBRATES