The antibodies causing thyroid stimulating hormone-binding inhibition (TSH-BI) are not responsible for the specific inhibition of gonadal steroidogenesis by Graves' sera.
Graves' disease is attributed to the presence of autoantibodies with agonist activity which interact with the TSH receptor causing thyroid hyperstimulation and hyperthyroidism. The degree of TSH-binding inhibition (TSH-BI) caused by a Graves' serum in a TSH radioligand receptor assay is considered to be an index of the prevalence of anti-TSH receptor autoantibodies in that serum. We have previously shown that the specific inhibition by Graves' serum of hCG-stimulated steroidogenesis by Leydig cells was at a site distal to receptor binding and second messenger activation. In this report, we have investigated whether the effect of Graves' serum upon Leydig cells is a property of the constitutive antibodies. Immunoglobulin-enriched fractions were obtained from Graves' and normal sera using three increasingly rigorous procedures; ammonium sulphate precipitation, caprylic acid treatment and Protein A or G-affinity purification. The TSH-BI was determined for untreated and extracted sera in two radioreceptor assays developed for use with serum, one using human thyroid membranes and the other using HeLa cells transfected with the human TSH receptor, and the results were compared with effects in the Leydig cell steroidogenesis bioassay. The specific inhibition of hCG-stimulated Leydig cell steroidogenesis by Graves' sera was not retained in the antibody fraction causing TSH-BI. Thus, the inhibitory factor appears not to be an antibody and we are now attempting to purify and identify the responsible factor from Graves' serum.
Castel
M A
MA
Institute for Hormone and Fertility Research at the University of Hamburg, Germany.
Willey
K P
KP
Hunt
N
N
Leidenberger
F
F
D000645:Ammonium Sulfate / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000494:pharmacology*; D002210:Caprylates / Q000494:pharmacology; D006111:Graves Disease / Q000097:blood* / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D012685:Sepharose; D013205:Staphylococcal Protein A / Q000494:pharmacology; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000166:cytology; D013972:Thyrotropin / Q000037:antagonists & inhibitors* / Q000276:immunology*
D001323:Autoantibodies; D002210:Caprylates; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D013739:Testosterone; D013972:Thyrotropin; D012685:Sepharose; C031492:octanoic acid; D000645:Ammonium Sulfate