Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats

Jeffrey S. Davies; Pia Kotokorpi; Ulrika Lindahl; Jan Oscarsson; Timothy Wells; Agneta Mode

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Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats

机译：合成肝X受体激动剂T0901317对雄性大鼠生长激素和甲状腺激素轴的影响

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Liver X receptors (LXRs), activated by oxysterols, play an important role in the regulation of lipid and glucose metabolism, which is also markedly dependent on thyroid hormone and growth hormone (GH) status. Here, we investigated how a 1-week exposure to the synthetic LXR agonist T0901317 affected GH secretion and thyroid hormone status in male rats. While the pulse frequency of GH secretion was marginally affected there was a highly significant decrease in the triiodo-l-thyronine/thyroxine (T3/T4) ratio in plasma. This effect was associated with decreased expression of deiodinase 1 (DIO1) and 2 (DIO2) mRNA in the liver and thyroid gland, respectively. Expression of sterol regulatory element binding protein-1c (SREBP-1c), the hallmark of stimulated lipogenesis, was markedly increased in both thyroid and pituitary implying that protracted pharmacological LXR activation may promote lipid accumulation in these endocrine tissues. These findings suggest that attention must be given to pituitary hormone dependent axes when developing therapeutic strategies based on agonism of the LXRs, e.g. for treatment of atherosclerosis.

机译：氧固醇激活的肝X受体（LXRs）在脂质和葡萄糖代谢的调节中起着重要作用，后者也明显依赖于甲状腺激素和生长激素（GH）的状态。在这里，我们调查了暴露于合成LXR激动剂T0901317 1周对雄性大鼠的GH分泌和甲状腺激素状态的影响。虽然GH分泌的脉冲频率受到轻微影响，但血浆中的三碘-1-甲状腺素/甲状腺素（T3 / T4）比率却大大降低。此作用分别与肝脏和甲状腺中去碘酶1（DIO1）和2（DIO2）mRNA的表达降低有关。固醇调节元件结合蛋白1c（SREBP-1c）的表达（受刺激的脂肪生成的标志）在甲状腺和垂体中均显着增加，这表明长期的药理学LXR活化可能促进这些内分泌组织中脂质的积累。这些发现表明，在开发基于LXRs的激动作用的治疗策略时，例如垂体激素依赖的垂体激素依赖性轴必须引起重视。用于治疗动脉粥样硬化。

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来源
《Endocrine》 |2008年第2期|196-204|共9页
作者
Jeffrey S. Davies; Pia Kotokorpi; Ulrika Lindahl; Jan Oscarsson; Timothy Wells; Agneta Mode;
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作者单位

School of Biosciences Cardiff University Museum Avenue Cardiff CF10 3US UK;

Department of Biosciences and Nutrition Karolinska Institutet Novum 141 57 Huddinge Sweden;

AstraZeneca RampampD 431 83 Molndal Sweden;

AstraZeneca RampampD 431 83 Molndal Sweden;

School of Biosciences Cardiff University Museum Avenue Cardiff CF10 3US UK;

Department of Biosciences and Nutrition Karolinska Institutet Novum 141 57 Huddinge Sweden;

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正文语种 eng
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关键词
LXR; Liver; Thyroid; Pituitary; GH; T3; T4; Rat;

机译：LXR;肝;甲状腺;垂体;GH;T3;T4;大鼠;

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专利

1. Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats. [J] . Davies JS, Kotokorpi P, Lindahl U, Endocrine. . 2008,第2期

机译：合成肝X受体激动剂T0901317对雄性大鼠生长激素和甲状腺激素轴的影响。
2. Effects of caloric restriction and growth hormone resistance on the expression level of peroxisome proliferator-activated receptors superfamily in liver of normal and long-lived growth hormone receptor/binding protein knockout mice. [J] . Masternak MM, Al-Regaiey KA, Del-Rosario-Lim MM, The journals of gerontology.Series A. Biological sciences and medical sciences . 2005,第11期

机译：热量限制和生长激素抵抗对正常和长寿生长激素受体/结合蛋白敲除小鼠肝脏中过氧化物酶体增殖物激活受体超家族表达水平的影响。
3. Ligand-dependent, Pit-1/growth hormone factor-1 (GHF-1)-independent transcriptional stimulation of rat growth hormone gene expression by thyroid hormone receptors in vitro. [J] . C S Suen, W W Chin Molecular and Cellular Biology . 1993,第3期

机译：配体依赖性，Pit-1 /生长激素因子-1（GHF-1）依赖性转录刺激大鼠甲状腺激素受体对大鼠生长激素基因表达的影响。
4. Expression of thyroid hormone receptor-alpha in the growth and development of the sea bream (sparus aurata) [C] . Lynda Llewellyn, Vimi P. Ramsurn, Trevor Wigham, International marine biotechnology conference . 1998

机译：甲状腺激素受体-α在鲷鱼（金头鲷）的生长和发育中的表达
5. Glycoprotein hormone receptors in sea lamprey (Petromyzon marinus): Identification, characterization and implications for the evolution of the vertebrate hypothalamic-pituitary-gonadal/thyroid axes [D] . Freamat, Mihael 2007

机译：海七rey（Petromyzon marinus）中的糖蛋白激素受体：脊椎动物下丘脑-垂体-性腺/甲状腺轴的进化，鉴定和表征
6. Ligand-dependent Pit-1/growth hormone factor-1 (GHF-1)-independent transcriptional stimulation of rat growth hormone gene expression by thyroid hormone receptors in vitro. [O] . C S Suen, W W Chin 1993

机译：甲状腺激素受体在体外对大鼠生长激素基因表达的配体依赖性Pit-1 /生长激素因子-1（GHF-1）独立的转录刺激。
7. Differential effects of triiodothyronine and the thyroid hormone receptor ß-Specific agonist GC-1 on thyroid hormone target genes in the brain [O] . Manzano, Jimena, Morte, Beatriz, Scanlan, Thomas S., 2003

机译：三碘甲状腺素和甲状腺激素受体β-特异性激动剂GC-1对脑中甲状腺激素靶基因的差异作用
8. Effects of Repeated Stress on Pituitary Cyclic AMP, and Plasma Prolactin, Corticosterone and Growth Hormone in Male Rats. [R] . Kant, G. J., Bunnell, B. N., Mougey, E. H., 1983

机译：重复应激对雄性大鼠垂体环amp，血浆催乳素，皮质酮和生长激素的影响。

Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats

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