Inhibition of follicle-stimulating hormone receptor binding by circulating immunoglobulins

We have characterized a circulating inhibitor of FSH receptor binding found in two patients with hypergonadotropic amenorrhea and myasthenia gravis. The inhibitor behaves as an immunoglobulin according to several criteria, including precipitation by 30% ammonium sulfate, migration on DEAE-cellulose chromatography, specific binding to protein A-Sepharose, characterization as a 7S protein in sucrose density gradients, and immunoprecipitation with specific antihuman immunoglobulin G. Evidence suggests that these antibodies are directed at determinants on or near the FSH receptor, and they may be responsible for the observed clinical FSH resistance.