Helbing Caren C, Crump Kate, Bailey Carmen M, Kohno Satomi, Veldhoen Nik, Bryan Teresa, Bermudez Dieldrich, Guillette Louis J
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Gen Comp Endocrinol. 2006 Nov;149(2):141-50. doi: 10.1016/j.ygcen.2006.05.019. Epub 2006 Aug 1.
Thyroid hormones (THs) play key regulatory roles in growth, development and metabolism in vertebrates. Modulation of the cellular hormonal response is largely through the activity of two nuclear TH receptors, TRalpha and TRbeta, which act as transcription factors and alter gene expression programs. Little information is available regarding their structure and regulation in reptiles. We have cloned the expressed sequences encoding these two receptors in the American alligator, Alligator mississippiensis. The encoded putative proteins share a high degree of amino acid sequence conservation with other vertebrates, however, both alligator TRs contain putative N-terminal truncations. This phenomenon is shared with the chicken for TRbeta, but not for TRalpha, making this the first demonstration of this type of TRalpha isoform. We measured the steady-state levels of TR transcripts in heart, lung, liver, thyroid, cliterophallus/phallus, and gonad of juvenile alligators 24 and 48 h after injection with thyroid stimulating hormone (TSH). TRalpha transcript levels were increased in the heart, decreased in the lung and cliterophallus/phallus, and unaffected in the liver, thyroid, and gonad. TRbeta transcript levels were increased in the heart, lung, and gonad whereas estrogen receptor alpha transcript levels were elevated by TSH treatment only in the gonad. Modulation of these transcripts in the gonad is consistent with TH playing an important role in this tissue's function since seasonal TH fluctuations coincide with reproductive events. These data demonstrate that alligator tissues are differentially responsive to TSH by regulation of TR expression and provide an important comparative framework among vertebrates.
甲状腺激素(THs)在脊椎动物的生长、发育和新陈代谢中发挥着关键的调节作用。细胞对激素的反应调节主要通过两种核甲状腺激素受体TRα和TRβ的活性来实现,这两种受体作为转录因子,可改变基因表达程序。关于它们在爬行动物中的结构和调节,目前所知甚少。我们已经克隆了美国短吻鳄(密西西比鳄)中编码这两种受体的表达序列。编码的假定蛋白质与其他脊椎动物具有高度的氨基酸序列保守性,然而,两种短吻鳄TRs都包含假定的N端截短。这种现象在鸡的TRβ中也存在,但TRα不存在,这是这种类型的TRα异构体的首次证明。我们测量了幼年短吻鳄在注射促甲状腺激素(TSH)后24小时和48小时,心脏、肺、肝脏、甲状腺、阴蒂/阴茎和性腺中TR转录本的稳态水平。TRα转录本水平在心脏中升高,在肺和阴蒂/阴茎中降低,在肝脏、甲状腺和性腺中不受影响。TRβ转录本水平在心脏、肺和性腺中升高,而雌激素受体α转录本水平仅在性腺中因TSH处理而升高。性腺中这些转录本的调节与TH在该组织功能中发挥重要作用一致,因为季节性TH波动与生殖事件相吻合。这些数据表明,短吻鳄组织通过TR表达的调节对TSH有不同的反应,并为脊椎动物提供了一个重要的比较框架。