The biochemistry of autonomous thyroid nodules: clues on the pathogenesis.
The "in vitro" characteristics of H2O2 generation, iodide, cAMP and PI metabolism, have been compared in tissues from autonomously functioning thyroid nodules and their quiescent counterpart to test the hypothesis that autonomy may result from constitutive activation of the tissue's TSH-IP's, or TSH-cAMP regulatory pathway. The enhanced iodide uptake is entirely due to increased transport capacity, the affinity of iodide transport and the fractional binding of iodide to protein remaining unchanged. The basal IP's accumulation is slightly higher in seven cases where it was studied but the response to TSH was markedly decreased. The cAMP-protein phosphorylation regulatory axis is not constitutively activated. Under TSH and forskolin stimulation, a 20K protein is not phosphorylated in nodular tissue as it is in its quiescent counterpart. The others, possible points of deviation in the cAMP cascade, studied in these tissues, i.e. basal cyclic AMP, desensitization to TSH, iodide inhibition, responses to other hormones or neurotransmitters were not systematically different in nodular tissue. The 20K protein, not phosphorylated in response to TSH in the nodules, could represent an absent negative controlling element. The absence of a 20K protein substrate of cAMP dependent protein kinases remains the most interesting clue about the mechanism of autonomy. We are now trying to purify and clone this protein.
Van Sande
J
J
Institute of Interdisciplinary Research, School of medicine, Free University of Brussels, Belgium.
Corvilain
B
B
Laurent
E
E
Lejeune
C
C
Rocmans
P
P
Mockel
J
J
Dumont
J E
JE
D000262:Adenylyl Cyclases / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006980:Hyperthyroidism / Q000000981:diagnostic imaging*; D007455:Iodine / Q000378:metabolism; D007457:Iodine Radioisotopes; D011494:Protein Kinases / Q000502:physiology; D011877:Radionuclide Imaging; D013959:Thyroid Diseases / Q000000981:diagnostic imaging*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging*
D007457:Iodine Radioisotopes; D007455:Iodine; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D011494:Protein Kinases; D000262:Adenylyl Cyclases