Pisarev M A, Chazenbalk G D, Valsecchi R M, Burton G, Krawiec L, Monteagudo E, Juvenal G J, Boado R J, Chester H A
Depto. Aplicaciones Biologicas, Comision Nacional de Energia Atomica, Buenos Aires, Argentina.
J Endocrinol Invest. 1988 Oct;11(9):669-74. doi: 10.1007/BF03350212.
Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompund. Data from different laboratories have shown that the thyroid is capable of producing different iodolipids, including iodinated derivatives of arachidonic acid; such as 5-hydroxy-6-iodo-8, 11, 14-eicosatrienoic-delta-lactone (IL-delta). Previous results from our laboratory showed that a semi-purified preparation of iodinated arachidonic acid exerts an inhibitory action in vitro on calf thyroid. In the present studies three purified iodinated derivatives of arachidonic acid were synthesized: IL-delta; 14-iodo-15-hydroxy-5, 8, 11-eicosatrienoic acid (I-OH-A) and its corresponding omega-lactone (IL-omega). Their action on MMI-induced goiter was studied in rats. Administration of MMI to rats during 10 days increased thyroid weight by 124%. This effect was significantly inhibited by the simultaneous injection of 5 micrograms/day of I-OH-A (57% inhibition of MMI action), IL-W (39%), IL-delta (33%) and T3 (95%), while arachidonic acid was without action. No inhibition was found with 1.25 micrograms/day Kl, a dose equivalent to that which could be originated from total dehalogenation of the iodocompounds. These results support the idea that these iodocompounds have an intrinsic biologic activity and that there is a correlation between action and chemical structure. Serum TSH was increased around 15-20 fold after MMI administration. Chronic or acute injection of I-OH-A failed to alter TSH levels, indicating that this iodocompound exerts its action directly on the gland, without altering TSH concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
甲状腺自身调节与一种未知假定碘化合物的腺体内含量有关。来自不同实验室的数据表明，甲状腺能够产生不同的碘脂质，包括花生四烯酸的碘化衍生物，如5-羟基-6-碘-8,11,14-二十碳三烯酸-δ-内酯（IL-δ）。我们实验室之前的结果表明，一种半纯化的碘化花生四烯酸制剂在体外对小牛甲状腺有抑制作用。在本研究中，合成了三种纯化的花生四烯酸碘化衍生物：IL-δ、14-碘-15-羟基-5,8,11-二十碳三烯酸（I-OH-A）及其相应的ω-内酯（IL-ω）。研究了它们对甲巯咪唑（MMI）诱导的大鼠甲状腺肿的作用。给大鼠连续10天给予MMI可使甲状腺重量增加124%。同时注射5微克/天的I-OH-A（对MMI作用的抑制率为57%）、IL-ω（39%）、IL-δ（33%）和T3（95%）可显著抑制这种作用，而花生四烯酸则无作用。1.25微克/天的碘化钾（KI）没有抑制作用，该剂量相当于碘化合物完全脱卤可能产生的剂量。这些结果支持了这些碘化合物具有内在生物活性的观点，并且作用与化学结构之间存在相关性。给予MMI后，血清促甲状腺激素（TSH）升高约15至20倍。慢性或急性注射I-OH-A未能改变TSH水平，表明这种碘化合物直接作用于腺体，而不改变TSH浓度。（摘要截断于250字）
