PMID- 20825298
OWN - NLM
STAT- MEDLINE
DCOM- 20110103
LR  - 20131121
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Linking)
VI  - 20
IP  - 9
DP  - 2010 Sep
TI  - Biochemical changes during goiter induction by methylmercaptoimidazol and 
      inhibition by delta-iodolactone in rat.
PG  - 1003-13
LID - 10.1089/thy.2009.0257 [doi]
AB  - BACKGROUND: We have demonstrated that the administration of delta-iodolactone 
      (i.e., 5-iodo-delta lactone) of arachidonic acid (IL-delta), a mediator in 
      thyroid autoregulation, prevents goiter induction by methylmercaptoimidazol (MMI) 
      in rats. Other studies have shown that transforming growth factor beta-1 
      (TGF-beta1) mimics some of the actions of excess iodide, but its participation in 
      autoregulation is disputed. The present studies were performed to test the 
      hypotheses that IL-delta decreases thyroid growth by inhibition of cell 
      proliferation and/or by stimulation of apoptosis due to oxidative stress, that 
      TGF-beta is stimulated by an excess of iodide and by IL-delta, and that c-Myc and 
      c-Fos expression are upregulated during goiter induction and downregulated during 
      goiter inhibition. METHODS: Rats were treated with MMI alone or together with 
      iodide or IL-delta. Thyroid weight, cell number, cell proliferation, apoptosis, 
      and oxidative stress were determined. Proliferating cell nuclear antigen (PCNA), 
      TGF-beta1, TGF-beta3, c-Myc, and c-Fos were measured by Western blot. RESULTS: 
      MMI caused a progressive increase in thyroid weight accompanied by an increase in 
      cell number, asymmetry of the ploidy histograms, and PCNA, c-Fos, and c-Myc 
      expression. In addition, an early increase of apoptosis was observed. Peroxides 
      as well as glutathione peroxidase and catalase activities were also increased in 
      goitrous animals. The inhibitory action of IL-delta on goiter formation was 
      accompanied by the inhibition of cell proliferation evidenced by a significant 
      decrease in cell number, PCNA expression, and asymmetry of the ploidy histograms. 
      A transient stimulation of apoptosis after 7 days of treatment was also observed. 
      MMI administration stimulated TGF-beta1 but not TGF-beta3 synthesis. IL-delta 
      alone caused a slight increase of TGF-beta3 but not TGF-beta1, whereas potassium 
      iodide (KI) stimulated both isoforms and MMI reversed KI effect on TGF-beta1 
      expression but not on TGF-beta3. CONCLUSIONS: The goiter inhibitory action of 
      IL-delta is due to the inhibition of cell proliferation and the transient 
      stimulation of apoptosis. This latter action does not involve oxidative stress. 
      TGF-beta1 does not play a role in the autoregulatory pathway mediated by 
      IL-delta. Iodide stimulates TGF-beta3 without the need of being organified. These 
      results suggest that there may be more than one pathway involved in the 
      autoregulatory mechanism.
FAU - Thomasz, Lisa
AU  - Thomasz L
AD  - Nuclear Biochemistry Division, Department of Radiobiology, National Atomic Energy 
      Commission, Buenos Aires, Argentina.
FAU - Oglio, Romina
AU  - Oglio R
FAU - Randi, Andrea S
AU  - Randi AS
FAU - Fernandez, Marina
AU  - Fernandez M
FAU - Dagrosa, Maria A
AU  - Dagrosa MA
FAU - Cabrini, Romulo L
AU  - Cabrini RL
FAU - Juvenal, Guillermo J
AU  - Juvenal GJ
FAU - Pisarev, Mario A
AU  - Pisarev MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (6-iodo-5-hydroxy-eicosatrienoic acid, delta-lactone)
RN  - 0 (Arachidonic Acids)
RN  - 0 (Peroxides)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Transforming Growth Factor beta3)
RN  - 554Z48XN5E (Methimazole)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Arachidonic Acids/*therapeutic use
MH  - Catalase/analysis
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Glutathione Peroxidase/analysis
MH  - Goiter/chemically induced/*prevention & control
MH  - Methimazole/toxicity
MH  - Oxidative Stress/drug effects
MH  - Peroxides/analysis
MH  - Proliferating Cell Nuclear Antigen/analysis
MH  - Proto-Oncogene Proteins c-fos/analysis
MH  - Proto-Oncogene Proteins c-myc/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Thyroid Gland/drug effects/metabolism
MH  - Transforming Growth Factor beta1/analysis
MH  - Transforming Growth Factor beta3/analysis
EDAT- 2010/09/10 06:00
MHDA- 2011/01/05 06:00
CRDT- 2010/09/10 06:00
PHST- 2010/09/10 06:00 [entrez]
PHST- 2010/09/10 06:00 [pubmed]
PHST- 2011/01/05 06:00 [medline]
AID - 10.1089/thy.2009.0257 [doi]
PST - ppublish
SO  - Thyroid. 2010 Sep;20(9):1003-13. doi: 10.1089/thy.2009.0257.