THEHUMENPERSPECTIVE-首都师范大学网重点分析.pptVIP

THE HUMEN PERSPECTIVE Disorders Associated with G protein-Coupled Receptors 腺瘤 腺瘤（adenoma）起源于腺上皮，常见于甲状腺、乳腺、胃肠道、涎腺、卵巢等处，也可发生于肾上腺皮质、甲状旁腺等内分泌腺。 发生于腺器官的腺瘤多呈结节状，常有包膜，界限清楚。发生于粘膜面的腺瘤多呈息肉状。分化较好的腺瘤常具有相应的分泌功能，如 胃肠道腺瘤可分泌粘液；内分泌腺腺瘤可分泌相应的激素等。 腺瘤的常见类型有：①息肉状腺瘤：多发生于胃肠道粘膜，呈息肉状，借细蒂与粘膜相连，可单发或多发（图4-13），其中大肠绒毛状腺瘤和家族性多发性结肠息肉易癌变； ②纤维腺瘤：肿瘤多为单个，常见于女性乳腺，呈结节状或分叶状，境界清楚，切面呈灰白色、半透明状。镜下特点是乳腺导管上皮细胞和周围的结缔组织同时增生，两者共同构成肿瘤的实质 ③多形性腺瘤：起源于涎腺闰管上皮和肌上皮细胞，常见于腮腺、颌下腺和舌下腺等处，肿瘤呈结节状，有包膜。镜下,由腺管、鳞状上皮、粘液样和软骨样等多种成分构成。手术切除不彻底易复发，多次复发可恶变，是一种交界性肿瘤； ④囊腺瘤：常见于卵巢，也可发生于胰腺和甲状腺。由于瘤细胞分泌大量粘液或浆液，使腺腔逐渐扩大并融合成大小不等的囊腔，故肿瘤呈囊性。瘤细胞可向囊腔内呈乳头状增生，形成乳头状囊腺瘤，如卵巢的浆液性乳头状囊腺瘤，易发生癌变。 thyroid adenoma （甲状腺瘤） Mutations that lead to a gain of function. mutations have been found to cause a type of benign thyroid tumor, called an adenoma. CNDI是由于突变导致编码的受体丧失功能而产生的.但很多使信号转导蛋白结构发生改变的突变却可以产生一种相反的效应,导致一种被描述为“机能增益”的现象. thyroid adenoma （甲状腺瘤） Unlike normal thyroid cells that secrete thyroid hormone only in response to stimulation by the pituitary(垂体的) hormone TSH（促甲状腺激素）, the cell of these thyroid adenomas secrete large quantities of thyroid hormone without having to be stimulated by TSH (the receptor is said to act constitutively). How Does This Happen? The TSH receptor in these cells contains an amino acid substitution that affects the structure of the third intracellular loop of the protein (mutations at sites 5 or 6). thyroid adenoma （甲状腺瘤） 　As a result of the mutation, the TSH receptor constitutively activates a G protein on its inner surface, sending a continual signal through the pathway that leads not only to excessive thyroid hormone secretion but to the excessive cell proliferation that causes the tumor. This conclusion was verified by introducing the mutant gene into cultured cells that normally lack this receptor and demonstrating that the synthesis of the mutant protein and its incorporation into the plasma membrane led to the continuous production of cAMP in the genetically engineered cells. Adeno