Fischer J A, Tobler P H, Kaufmann M, Born W, Henke H, Cooper P E, Sagar S M, Martin J B
Proc Natl Acad Sci U S A. 1981 Dec;78(12):7801-5. doi: 10.1073/pnas.78.12.7801.
Immunoreactive calcitonin (CT), indistinguishable from human CT-(1-32) and its sulfoxide, has been identified in extracts of the hypothalamus, the pituitary, and the thyroid obtained from human subjects at autopsy. DCT concentrations were highest in a region encompassing the posterior hypothalamus, the median eminence, and the pituitary; intermediate in the substantia nigra, the anterior hypothalamus, the globus pallidus, and the inferior colliculus; and low in the caudate nucleus, the hippocampus, the amygdala, and the cerebral and cerebellar cortices. Specific CT binding measured with 125I-labeled salmon CT was highest in homogenates of the posterior hypothalamus and the median eminence, shown to contain the highest concentrations of endogenous CT in the brain; CT binding was less than 12% of hypothalamic binding in all of the other regions of the brain examined and was negligible in the pituitary. Half-maximal binding was achieved with 0.1 nM nonradioactive salmon CT-(1-32), and the binding was directed to structural or conformational sites, or both, in the COOH-terminal half of salmon CT. The rank order of the inhibition of the binding by CT from different species and analogues of the human hormone was the same as in receptors on a human lymphoid cell line (Moran, J., Hunziker, W. & Fischer, J. A. (1978) Proc. Natl. Acad. Sci. USA 75, 3984-3988). The functional role of CT and of its binding sites in the brain remains to be elucidated.
在尸检时从人类受试者获取的下丘脑、垂体和甲状腺提取物中,已鉴定出与人类CT-(1-32)及其亚砜无法区分的免疫反应性降钙素(CT)。降钙素基因相关肽(DCT)浓度在下丘脑后部、正中隆起和垂体周围区域最高;在黑质、下丘脑前部、苍白球和下丘脑中为中等水平;在尾状核、海马、杏仁核以及大脑和小脑皮质中较低。用125I标记的鲑鱼降钙素测量的特异性CT结合,在下丘脑后部和正中隆起的匀浆中最高,这些部位被证明是大脑中内源性CT浓度最高的地方;在所有其他检查的脑区中,CT结合量不到下丘脑结合量的12%,在垂体中可忽略不计。用0.1 nM非放射性鲑鱼CT-(1-32)可达到最大结合量的一半,且这种结合针对鲑鱼降钙素COOH末端一半中的结构或构象位点,或两者兼而有之。不同物种的CT和人类激素类似物对结合的抑制作用的排序与人类淋巴细胞系上的受体相同(莫兰,J.,洪齐克,W.和菲舍尔,J.A.(1978年)《美国国家科学院院刊》75,3984-3988)。CT及其在大脑中的结合位点的功能作用仍有待阐明。