Div. Bioquímica Nuclear, CNEA, Av. Del Libertador 8250, Buenos Aires 1429, Argentina.
Mol Cell Endocrinol. 2010 Apr 12;317(1-2):141-7. doi: 10.1016/j.mce.2009.12.026. Epub 2009 Dec 29.
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.
to study the action of 2-IHDA on methimazole (MMI)-induced goiter and analyze if this compound can cause the involution of preformed goiter.
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.
2-Iodohexadecanal, as 6-iodo-deltalactone, prevents goiter growth in rats and opens a potential therapeutic application of iodolipids.
甲状腺的自身调节与一种未知的假定碘化合物的腺内含量有关。甲状腺能够产生不同的碘脂,如 6-碘-delta-内脂(ILdelta)和 2-碘十六烷醛(2-IHDA)。来自不同实验室的数据表明,这些碘脂抑制了几种甲状腺参数。ILdelta 具有抗甲状腺肿作用,但尚无关于 2-IHDA 对该参数作用的报道。
研究 2-IHDA 对甲巯咪唑(MMI)诱导的甲状腺肿的作用,并分析该化合物是否能导致预先形成的甲状腺肿的退化。
MMI 连续 10 天给药可使大鼠甲状腺重量增加 112%。同时注射 20μg/天的 2-IHDA(51%与 MMI 相比)可显著抑制此作用,而碘或非碘代十六烷醛则无此作用。甲状腺增殖细胞核抗原(PCNA)含量在 MMI 给药后增加,而 2-IHDA 降低了该值(对照:100%;MMI:190+/-11;MMI+2-IHDA:134+/-10)。MMI 给药后血清 TSH 增加,而 2-IHDA 未改变该参数(对照:1.89+/-0.10;MMI:8.19+/-0.93ng/ml;MMI+2-IHDA:7.38+/-0.72)。MMI 治疗增加了甲状腺 cAMP 含量(对照:16.1+/-0.82,MMI:42.4+/-4.6fmol/mg 蛋白),而 2-IHDA 则显著降低了该值(22.3+/-2.0)。2-IHDA 还可预防 30 天治疗时的甲状腺肿,减少总细胞数(51%抑制)和上皮高度(81%抑制)。在停用 MMI 并注射 2-IHDA、KI 或生理盐水后,诱导甲状腺肿消退。2-IHDA 在 3 天后使甲状腺重量减少 74.5%,而自发消退(生理盐水)仅为 32%。KI 未能改变该值。这种显著的消退伴随着细胞数量的减少(66%)。碘脂给药未引起总 T(3)和 T(4)、胆固醇、转氨酶、尿素和肌酐等血清参数的显著变化。
2-碘十六烷醛与 6-碘-delta-内脂一样,可预防大鼠甲状腺肿的生长,并为碘脂的潜在治疗应用开辟了道路。