Possible involvement of organic anion transporting polypeptide 1c1 in the photoperiodic response of gonads in birds

Possible involvement of organic anion transporting polypeptide 1c1 in the photoperiodic response of gonads in birds
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DOI:
10.1210/en.2005-1090
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发表时间:
2006-03-01
期刊:
影响因子:
4.8
通讯作者:
Yoshimura, T
Yoshimura, T
中科院分区:
医学2区
文献类型:
--
作者:
Nakao, N;Takagi, T;Yoshimura, T

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性腺的光周期反应需要T-3,T-4是由下丘脑中的2型碘甲状腺原氨酸脱碘酶在光周期中产生的。尽管甲状腺激素由于其亲脂性而被认为是通过被动扩散穿过质膜,但现在人们知道几种有机阴离子转运多肽(OATP)将甲状腺激素转运到靶细胞。在本研究中,我们使用数据库搜索的方法分离了编码鸡Oatp家族成员的DNA序列,并构建了分子系统发育树。原位杂交综合表达分析显示,cOatp1c1在下丘脑基底结节腹外侧壁表达较强,cOatp1b1表达较弱,而cOatp1a1、cOatp1b1、cOatp1c1和cOatp3a2基因在脉络丛有表达。在短日照和长日照条件下,所有这些基因在这两个区域的表达水平没有差别。COatp1c1在中国仓鼠卵巢细胞中的功能表达表明,cOatp1c1是一种高度特异的T-4转运蛋白,其表观Km值为6.8 nM,Vmax为1.50pmoL/毫克蛋白质/分钟。这些结果表明,cOatp1c1可能参与了鸟类性腺光周期反应所必需的甲状腺素运输。
The photoperiodic response of the gonads requires T-3, which is generated photoperiodically from T-4 by type 2 iodothyronine deiodinase in the hypothalamus. Although thyroid hormones were long thought to traverse the plasma membrane by passive diffusion due to their lipophilic nature, it is now known that several organic anion transporting polypeptides (Oatp) transport thyroid hormones into target cells. In this study, we have used database searches to isolate DNA sequences encoding members of the chicken Oatp family and constructed a molecular phylogenetic tree. Comprehensive expression analyses using in situ hybridization revealed strong expression of cOatp1c1 and weak expression of cOatp1b1 in the ventro-lateral walls of basal tuberal hypothalamus, whereas expression of four genes (cOatp1a1, cOatp1b1, cOatp1c1, and cOatp3a2) was observed in the choroid plexus. Expression levels of all these genes in both regions were not different between short-day and long-day conditions. Functional expression of cOatp1c1 in Chinese hamster ovary cells revealed that cOatp1c1 is a highly specific transporter for T-4 with an apparent Km of 6.8 nM and a Vmax of 1.50 pmol per milligram of protein per minute. These results suggest that cOatp1c1 could be involved in the thyroxine transport necessary for the avian photoperiodic response of the gonads.