Studies on the mode of action of TSBAb

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The thyroid stimulation blocking antibody (TSBAb) which block the stimulatory effect of TSH on thyroid has been suggested as the causal factor of hypothyroidism.There are two types of TSBAb, one type has a blocking action on TSH by its direct binding to the TSH receptor [TSH binding inhibitory immunoblobulin (TBII) positive blocking antibody] and the other type has a blocking action without affecting TSH binding to its receptor (TBII negative blocking antibody). The study on mode of action of TSBAb was performed.1. The action of TSBAb on thyroid cell membraneThe TSBAb with high TBII activities significantly blocked TSH-stimulated cAMP production in porcine thyroid cells (PTC). However, there was no blocking action of TSBAb on the cAMP increase stimulated by forskolin, GTP gamma S,or NaF in isolated porcine thyroid membrane (PTM). The TSBAb activity was absorbed with PTM,but was not absorbed with guinea-pig epididymal fat membrane in some cases in spite of the absorption of the TBII activity in TSBAb-IgG by these two membranes. This suggests that TSBAb may block TSH action either via the TSH receptor or via a non-TSH receptor component of the thyroid membrane and not at a post receptor level.2. Production of TSBAb in experimental rabbitsThe produced antibody in rabbits against PTM showed the TSBAb activity in spite of negative TBII activity. The fact suggests that this type of TSBAb may be produced against any antigen of thyroid membrane origin except the TSH receptor.3.Appearence of thyroid stimulating activity from TSBAb-IgG by protease digestionThe innocent action (without thyroid stimulating activity) of TSBAb-IgG was converted to the thyroid stimulating activity by protease digestion. The thyroid stimulating activity located in Fab and the much smaller component fraction.