Modification of the amounts of G proteins and of the activity of adenylyl cyclase in human benign thyroid tumours.
The possibility that a TSH post-receptor-binding defect is responsible for the pathogenesis of benign thyroid tumours was studied. Thus, we attempted to determine in hyperfunctioning (hot) nodules and non-functioning (cold) nodules whether the functional activity or the amount of G proteins were modified in comparison with surrounding normal tissues. The adenylyl cyclase response to agonists that bypass the TSH-receptor complex (forskolin, guanosine 5'- (beta.gamma-imido)triphosphate (Gpp(NH)p) or [AIF4]-) was studied on membranes from tumorous and adjacent normal thyroid tissues. We also examined the ability of G proteins to be ADP-ribosylated by cholera toxin (CT) or pertussis toxin (PT), and quantified G proteins by Western blot analysis with specific antisera directed against Gs alpha and Gi alpha subunits. Basal adenylyl cyclase activity was unchanged in hot tumours compared with normal tissue whereas the stimulation of adenylyl cyclase by Gpp(NH)p or [A1F4]- (which act directly on Gs) as well as by forskolin (which acts on the catalyst) was significantly (P less than 0.05) decreased in five of seven nodules studied. Two types of response were found in cold nodules, depending upon whether they were microfollicular or macrofollicular tumours. Basal as well as stimulated adenylyl cyclase activity was increased (0.02 less than P less than 0.05) in microfollicular tumours. In contrast, in macrofollicular tumours basal adenylyl cyclase was unchanged whereas stimulated adenylyl cyclase activity was decreased (0.02 less than P less than 0.05). The ability of Gs or Gi to be ADP-ribosylated by CT or PT respectively was maintained in tumorous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Delemer
B
B
U 96 INSERM, Le Kremlin-Bicêtre, France.
Dib
K
K
Patey
M
M
Jacquemin
C
C
Corrèze
C
C
D000236:Adenoma / Q000737:chemistry / Q000201:enzymology*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000737:chemistry / Q000201:enzymology*; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000201:enzymology*
D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases