Inhibitory effect of thyroid blocking antibody (TBAb) on the thyroid stimulatory effect of human chorionic gonadotropin (HCG) and equine chorionic gonadotropin (ECG).
We examined the inhibitory effect of thyroid blocking antibody (TBAb) on the thyroid stimulating activity of human chorionic gonadotropin (HCG) and equine CG (ECG). Five TBAb positive sera obtained from patients who had been hypothyroid but were currently on T4 treatment. The TSH binding inhibitory immunoglobulin (TBII) activities of the sera were 60-160 IU/L. Inhibition of TSH binding to the TSH receptor (TSHR) [TSH binding inhibition (TBI) activity] of HCG or ECG, and inhibition of TBAb on HCG or ECG-stimulated cAMP production were examined. Both HCG and ECG preparations showed weak TBI activity in the presence of small amounts of protein [bovine serum albumin (BSA)] but were negative in the presence of large amounts of protein [normal human serum (NHS) or BSA]. Four thousand IU/mL of HCG and ECG preparation caused cAMP production similar to 100 microU/mL of bovine (b) TSH. The inhibitory effect of TBAb on cAMP production by this amount of HCG or ECG was then examined. The inhibitory effect of TBAb on cAMP production by HCG and ECG was similar to bTSH, and TBAb positive sera with more than 40 IU/L TBII activity completely blocked cAMP production by HCG, ECG and bTSH. This suggests that common alpha -subunit of both HCG and TSH are involved in the inhibitory effect of TBAb. Previous reports demonstrated that the thyroid stimulating activity of thyroid stimulating antibody (TSAb) was blocked by deglycosylated HCG (competitive antagonist of TSH binding to TSHR). The fact and our present study suggest that TSH, HCG ECG, TSAb and TBAb have a similar binding site (alpha-subunit-mimicking binding site) on the TSH receptor.
Ochi
Yukio
Y
Research Institute for Production Development, Kyoto, Japan. k-y-ochi@blue.plala.or.jp
Hamazu
Masanari
M
Kajita
Yoshihiro
Y
Hachiya
Takashi
T
Hamaoki
Masaru
M
D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000494:pharmacology; D002417:Cattle; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006064:Gonadotropins, Equine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000276:immunology; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood / Q000494:pharmacology*; D011989:Receptors, Thyrotropin / Q000737:chemistry / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology; D013974:Thyroxine / Q000627:therapeutic use
D001798:Blood Proteins; D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; C094372:thyrotropin-binding inhibitory immunoglobulin; D012710:Serum Albumin, Bovine; D013972:Thyrotropin; D000242:Cyclic AMP; D013974:Thyroxine