THE ANTIBODIES CAUSING THYROID-STIMULATING HORMONE-BINDING INHIBITION(TSH-BI) ARE NOT RESPONSIBLE FOR THE SPECIFIC-INHIBITION OF GONADAL STEROIDOGENESIS BY GRAVES SERA
Ma. Castel et al., THE ANTIBODIES CAUSING THYROID-STIMULATING HORMONE-BINDING INHIBITION(TSH-BI) ARE NOT RESPONSIBLE FOR THE SPECIFIC-INHIBITION OF GONADAL STEROIDOGENESIS BY GRAVES SERA, Journal of reproductive immunology, 30(1), 1996, pp. 1-15
Graves' disease is attributed to the presence of autoantibodies with a
gonist activity which interact with the TSH receptor causing thyroid h
yperstimulation and hyperthyroidism. The degree of TSH-binding inhibit
ion (TSH-BI) caused by a Graves' serum in a TSH radioligand receptor a
ssay is considered to be an index of the prevalence of anti-TSH recept
or autoantibodies in that serum. We have previously shown that the spe
cific inhibition by Graves' serum of hCG-stimulated steroidogenesis by
Leydig cells was at a site distal to receptor binding and second mess
enger activation. In this report, we have investigated whether the eff
ect of Graves' serum upon Leydig cells is a property of the constituti
ve antibodies. Immunoglobulin-enriched fractions were obtained from Gr
aves' and normal sera using three increasingly rigorous procedures; am
monium sulphate precipitation, caprylic acid treatment and Protein A o
r G-affinity purification. The TSH-BI was determined for untreated and
extracted sera in two radioreceptor assays developed for use with ser
um, one using human thyroid membranes and the other using HeLa cells t
ransfected 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' s
era was not retained in the antibody fraction causing TSH-BI. Thus, th
e inhibitory factor appears not to be an antibody and we are now attem
pting to purify and identify the responsible factor from Graves' serum
.