thyroid adenoma （甲状腺瘤） Unlike normal thyroid cells that secrete thyroid hormone only in response to stimulation by the pituitary( 垂体的 ) hormone TSH （ 促甲状腺激素 ）, the cell of these thyroid adenomas secrete large quantities of thyroid hormone without having to be stimulated by TSH (the receptor is said to act constitutively). How Does This Happen?
The TSH receptor in these cells contains an amino acid substitution that affects the structure of the third intracellular loop of the protein (mutations at sites 5 or 6).
As a result of the mutation, the TSH receptor constitutively activates a G protein on its inner surface, sending a continual signal through the pathway that leads not only to excessive thyroid hormone secretion but to the excessive cell proliferation that causes the tumor.
This conclusion was verified by introducing the mutant gene into cultured cells that normally lack this receptor and demonstrating that the synthesis of the mutant protein and its incorporation into the plasma membrane led to the continuous production of cAMP in the genetically engineered cells.