TSH binding correlates with TSH-stimulated thyroid adenylate cyclase activity in human thyroid tissues.
Thyroid-stimulating hormone (TSH) stimulates adenylate cyclase (AC) activity and the growth and differentiation of thyroid cancers of follicular cell origin. Thyroid neoplasms generally have higher TSH-stimulated AC activity than normal thyroid tissue from the same patients. To determine whether differences in TSH receptors could account for the differences in AC activity, we studied the 8000 g membrane particulate fraction from 28 thyroid tissues (10 papillary carcinomas, 6 multinodular goiters, 4 follicular adenomas, 3 follicular carcinomas, 2 Graves, 1 normal, 1 Hürthle cell adenoma, and 1 thyroiditis). TSH receptors were measured by competitive inhibition using radioactive iodine-labeled bovine TSH (125I-bTSH). Maximal binding capacity (Bmax) and dissociation constant (Kd) were calculated by Scatchard analysis. AC activity was measured by the conversion of alpha-[32P]-ATP to [32P]-cAMP in the maximally (300 mU/ml) TSH-stimulated state. The basal and forskolin-stimulated (100 mmol/L) AC activity were also measured, and the ratios to TSH-stimulated AC activity were calculated (TSH/Basal ratio and TSH/Forskolin ratio). We found a strong correlation between the percent specific binding (%SB) of 125I-bTSH and TSH/Basal ratio (r = 0.70, p = 0.0001), between Bmax and the TSH/Basal ratio (r = 0.71, p = 0.001), between %SB and TSH/Forskolin ratio (r = 0.44, p = 0.02), and between Bmax and TSH/Forskolin ratio (r = 0.65, p = 0.0002). This strong correlation between TSH binding and the TSH-stimulated AC activity suggests that in some thyroid neoplasms the higher AC response to TSH may be due to an increased number of TSH receptors.
Duh
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QY
Surgical Service, Veterans Administration Medical Center, San Francisco, CA 94121.
Siperstein
A E
AE
Miller
R A
RA
Smeds
S
S
Clark
O H
OH
D000262:Adenylyl Cyclases / Q000378:metabolism*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D013959:Thyroid Diseases / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology
D011989:Receptors, Thyrotropin; D005576:Colforsin; D013972:Thyrotropin; D000262:Adenylyl Cyclases