Burgos Jonathan R, Iresjö Britt-Marie, Wärnåker Sara, Smedh Ulrika
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Brain Res. 2016 Jul 1;1642:278-286. doi: 10.1016/j.brainres.2016.04.007. Epub 2016 Apr 5.
Previous studies have shown that brain-derived thyroid-stimulating hormone (TSH) and its receptor (TSHr) are present in hypothalamic extracts. No studies investigating both the anatomical location and functional significance of putative TSHr proteins in specific central nervous system (CNS) nuclei involved in feeding controls have yet been conducted. The aim was thus to determine whether TSHr are present in nuclei associated with feeding behavior, and if such receptors may be functional.
Brain tissue from adult rats was analyzed for gene expression and receptor protein expression was investigated with immunohistochemistry and western blotting. To investigate whether putative TSHr may be functional, we evaluated food intake of rats given intraparenchymal nanoinjections of TSH into the nucleus of the solitary tract (NTS).
RT-qPCR confirmed previous reports that TSHr mRNA is expressed in CNS tissues of the adult rat. Immunohistochemistry showed TSHr-immunoreactivity in the arcuate, the ventromedial, the dorsomedial, and the paraventricular hypothalamic nuclei. We also found TSHr-ir in the dorsal hindbrain to be localized to the area postrema, NTS, dorsal motor nucleus of the vagus, and the hypoglossal motor nucleus. Further protein analysis with western blotting showed 120kDa TSHr-ir proteins present in the hypothalamus and brainstem. Injections of TSH into the NTS reduced food intake similar to the positive control, urocortin.
These data suggest that functional TSHr are present in the caudal brainstem and hypothalamic nuclei of relevance for feeding control as a possibly uncleaved holoreceptor, and highlights a hindbrain component to central TSH inhibition of food intake.
先前的研究表明，脑源性促甲状腺激素（TSH）及其受体（TSHr）存在于下丘脑提取物中。尚未有研究调查假定的TSHr蛋白在参与进食控制的特定中枢神经系统（CNS）核团中的解剖位置和功能意义。因此，本研究旨在确定TSHr是否存在于与进食行为相关的核团中，以及此类受体是否具有功能。
分析成年大鼠的脑组织基因表达，并通过免疫组织化学和蛋白质印迹法研究受体蛋白表达。为了研究假定的TSHr是否具有功能，我们评估了向孤束核（NTS）实质内纳米注射TSH的大鼠的食物摄入量。
RT-qPCR证实了先前的报道，即TSHr mRNA在成年大鼠的CNS组织中表达。免疫组织化学显示，在弓状核、腹内侧核、背内侧核和室旁下丘脑核中有TSHr免疫反应性。我们还发现，延髓背侧的TSHr免疫反应性定位于最后区、NTS、迷走神经背运动核和舌下运动核。进一步的蛋白质印迹分析显示，下丘脑和脑干中存在120kDa的TSHr免疫反应性蛋白。向NTS注射TSH可减少食物摄入量，类似于阳性对照尿皮质素。
这些数据表明，功能性TSHr作为一种可能未裂解的全受体存在于与进食控制相关的脑干尾部和下丘脑核团中，并突出了后脑成分在中枢TSH抑制食物摄入中的作用。
