Early changes during goiter production and involution in rats

RANDI, ANDREA SILVANA; THOMASZ, LISA; CABRINI, RÓMULO; BRANDIZZI, DANIEL; JUVENAL, GUILLERMO JUAN; KLEIMAN DE PISAREV, DIANA LEONOR; PISAREV, MARIO ALBERTO

Buenos Aires, Argentina

Congreso; 13th International Thyroid Congress; 2005

Latin American Thyroid Society, European Thyroid Association, American Thyroid Association and Asia & Oceania Thyroid Association

Iodine would inhibit thyroid proliferation via an organic intermediate (autoregulation).  5-iodo-delta lactone of arachidonic acid (IL) mimics the effects of excess iodine.  Although TGF-b1 shares some of the actions of iodine, there is still controversy about its participation in thyroid autoregulation.  These studies were performed to learn about the changes which occur in the early phases of goitrogenesis and during involution of goiter caused by KI or IL. Methods: rats were treated i.p. during 3 days: a-controls; b-MMI 10 mg/day; c- KI 10 ug/day; d- IL 10 ug/day; e- MMI+KI; f- MMI+IL. Thyroid weight/b.wt.x100 was determined. Expression of c-Myc, c-Fos, TGF-b1 and TGF-b3 were analyzed by Western blot.  DNA content was determined on Feulgen-stained sections with a microspectrophotometer.  Ploydi histogram, asymmetry and index of deviation from the diploid value (2cDi) were determined. Results: Thyroid weight was slightly increased (40%) by MMI, and IL but not KI partially reversed it.  Histometric parameters showed a 200% increase in cell proliferation under MMI (p<0.05) which was partially inhibited by IL but not by KI.  MMI increased c-Fos (160%) but not by KI or IL. c-Myc was increased (45%) by IL+MMI but not by MMI. TGF- b1was increased 54% by MMI and 110% by KI (p<0.05), but not by IL, and MMI partially inhibited the action of KI.  TGF-b3 was increased by KI (78%, p<0.05) and MMI did not alter this action. Conclusion: a) IL impaired goiter growth induced by MMI; b) c-Fos is related to goiter growth; c) c-Myc is related to the antiproliferative action of KI and IL; d) TGF-b1 increased during the early stages of goiter; e) since TGF-b1 was increased by KI but not by IL, and MMI only partially reversed this effect, it migth be concluded that KI acts via an autoregulatory-independent pathway. Asuuming that the autoregulatory mechanism follows the sequence iodine- IL- actions, it may be concluded that TGF-b1 does not participate in this process; f) TGF-b3 expression was also stimulated by KI, and this action was not modified by MMI, indicating autoregulatory independent mechanism.