Ritchie J W, Peter G J, Shi Y B, Taylor P M
Department of Anatomy, University of Dundee, Dundee, DD1 4HN, Scotland UK.
J Endocrinol. 1999 Nov;163(2):R5-9. doi: 10.1677/joe.0.163r005.
Thyroid hormone (TH) action and metabolism require hormone transport across cell membranes. We have investigated the possibility that TH are substrates of amino acid transport (System L) mediated by heterodimers of 4F2 heavy-chain (hc) and the light-chain (lc) permease IU12. Co-expression of 4F2hc and IU12 cDNAs injected into Xenopus oocytes induces saturable, Na(+) -independent transport of tri-iodothyronine (T(3)), thyroxine (T(4)) (K(m) of 1.8 and 6.3 microM respectively), tryptophan and phenylalanine. Induced TH and tryptophan uptakes are inhibited by excess BCH (synthetic System L substrate). Induced TH uptake is also inhibited by excess reverse tri-iodothyronine (rT(3)), but not by triodothyroacetic acid (TRIAC) (TH analogue lacking anamino acid moiety). T(3) and tryptophan exhibit reciprocal inhibition of their 4F2hc-IU12 induced uptake. Transport pathways produced by 4F2hc-lc permease complexes may therefore be important routes for movement and exchange of TH (as well as amino acids) across vertebrate cell membranes, with a potential role in modulating TH action.
甲状腺激素(TH)的作用和代谢需要激素跨细胞膜转运。我们研究了TH是否是由4F2重链(hc)和轻链(lc)通透酶IU12的异二聚体介导的氨基酸转运(L系统)的底物。将4F2hc和IU12的cDNA共注射到非洲爪蟾卵母细胞中,可诱导三碘甲状腺原氨酸(T3)、甲状腺素(T4)(Km分别为1.8和6.3微摩尔)、色氨酸和苯丙氨酸的可饱和、不依赖Na+的转运。过量的BCH(合成的L系统底物)可抑制诱导的TH和色氨酸摄取。过量的反式三碘甲状腺原氨酸(rT3)也可抑制诱导的TH摄取,但三碘甲状腺乙酸(TRIAC)(缺乏氨基酸部分的TH类似物)则无此作用。T3和色氨酸对其由4F2hc-IU12诱导的摄取表现出相互抑制作用。因此,由4F2hc-lc通透酶复合物产生的转运途径可能是TH(以及氨基酸)在脊椎动物细胞膜上移动和交换的重要途径,在调节TH作用方面具有潜在作用。