Epidermal growth factor receptors and adenylate cyclase activity in human thyroid tissues.
Thyroid stimulating hormone (TSH) and epidermal growth factor (EGF) are growth factors for some thyroid cells in cultures. We have previously found more EGF receptors in neoplastic human thyroid tissues than in normal thyroid tissues. We have also found a higher TSH-stimulated adenylate cyclase (AC) activity in neoplastic human thyroid tissues than in normal thyroid tissues. To clarify the relationship between the effect of EGF and TSH on thyroid tissue, we measured the binding of EGF and TSH and the basal, TSH-stimulated and forskolin-stimulated adenylate cyclase activity in 49 normal, hyperplastic and neoplastic human thyroid tissues (5 normal, 2 Hashimoto thyroiditis, 5 Graves' disease, 14 multinodular goiters, 9 follicular adenomas, 5 follicular carcinomas, 8 papillary carcinomas, and 1 undifferentiated carcinoma). Specific binding of EGF and TSH were measured by radioreceptor assays using competitive inhibition of radio-labeled ligand by unlabeled ligand. Basal, maximally (300 mU/ml) TSH-stimulated, and maximally (100 mM) forskolin-stimulated adenylate cyclase activities were also measured in the same membrane particulate fractions from the thyroid tissues. We found: neoplastic thyroid tissues bind more labeled EGF than nonneoplastic thyroid tissues; follicular adenomas and carcinomas have higher EGF binding than other thyroid tissues; a weak but significant correlation between specific EGF binding and specific TSH binding, and between specific EGF binding and TSH-stimulated adenylate cyclase activity of the thyroid membrane preparations. These findings are consistent with the hypothesis that TSH stimulates an increase in thyroid EGF receptors by increasing intracellular cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Duh
Q Y
QY
Surgical Service, Veterans Administration Medical Center, San Francisco, California 94121.
Siperstein
A E
AE
Miller
R A
RA
Sancho
J J
JJ
Demeure
M J
MJ
Clark
O H
OH
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*
D011989:Receptors, Thyrotropin; D066246:ErbB Receptors; D000262:Adenylyl Cyclases