Inhibition of goiter growth and of cyclic AMP formation in rat thyroid by 2-iodohexadecanal.
BACKGROUND
Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompound. The thyroid is capable of producing different iodolipids such as 6-iodo-deltalactone (ILdelta) and 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that these iodolipids inhibit several thyroid parameters. ILdelta has an antigoitrogenic action but no data about the action of 2-IHDA on this parameter has been published.


OBJECTIVE
to study the action of 2-IHDA on methimazole (MMI)-induced goiter and analyze if this compound can cause the involution of preformed goiter.


RESULTS
Administration of MMI to rats during 10 days increased thyroid weight by 112%. This effect was significantly inhibited by the simultaneous injection of 20mug/day of 2-IHDA (51% vs. MMI) while iodine or non iodinated hexadecanal were without action. Thyroidal proliferating cell nuclear antigen (PCNA) content was increased by MMI while 2-IHDA decreased this value (control: 100%; MMI: 190+/-11; MMI+2-IHDA: 134+/-10). Serum TSH was increased after MMI administration and 2-IHDA did not modify this parameter (control: 1.89+/-0.10; MMI: 8.19+/-0.93ng/ml; MMI+2-IHDA: 7.38+/-0.72). Treatment with MMI increased thyroidal cAMP content (control: 16.1+/-0.82, MMI: 42.4+/-4.6 fmol/mg protein) while injection of 2-IHDA significantly decreased this value (22.3+/-2.0). Goiter prevention by 2-IHDA was also observed at 30 days of treatment reducing total number of cells (51% inhibition) and epithelial height (81% inhibition). Goiter involution was induced after withdrawal of MMI and injection with 2-IHDA, KI or saline. 2-IHDA led to a reduction of 74.5% in thyroid weight after 3 days while spontaneous involution (saline) was only of 32%. KI failed to alter this value. This significant involution was accompanied by a reduction in the number of cells (66%). Administration of the iodolipids did not produce significant changes in several serum parameters such as total T(3) and T(4), cholesterol, transaminases, urea and creatinine.


CONCLUSIONS
2-Iodohexadecanal, as 6-iodo-deltalactone, prevents goiter growth in rats and opens a potential therapeutic application of iodolipids.
Thomasz
L
L
Div. Bioquímica Nuclear, CNEA, Av. Del Libertador 8250, Buenos Aires 1429, Argentina.
Oglio
R
R
Rivandeira
D Toro
DT
Dagrosa
M A
MA
Jahn
G
G
Pignataro
O P
OP
Piganataro
O P
OP
Sartorio
G
G
Pisarev
M A
MA
Juvenal
G J
GJ
D000447:Aldehydes / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006042:Goiter / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D008713:Methimazole; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000447:Aldehydes; D018809:Proliferating Cell Nuclear Antigen; D014284:Triiodothyronine; C065952:2-iodohexadecanal; D008713:Methimazole; D013972:Thyrotropin; D000242:Cyclic AMP; D013974:Thyroxine