高鑫－内分泌总论.ppt

1、1,内分泌系统疾病总 论Introduction to Endocrinology and Metabolic Diseases,复旦大学附属中山医院内分泌科 高鑫,2,History and development of Endocrinology (1),Roughly a hundred years ago, Starling coined the term hormone to describe secretin, a substance secreted by the small intestine into the blood stream to stimulate pancrea

2、tic secretion. In his Croonian Lectures, Starling considered the endo- crine and nervous systems as two distinct mechanisms for coordination and control of organ function. Thus, endocrinology found its first home in the discipline of mammalian physiology.,3,Work over the next several decades by bioc

3、hemists, physiologists, and clinical investigators led to the characterization of many hormones secreted into the blood stream from discrete glands or other organs. These investigators showed for the first time that diseases such as hypothyroidism and diabetes could be treated successfully by replac

4、ing specific hormones. These initial triumphs formed the foundation of the clinical specialty of endocrinology.,History and development of Endocrinology (2),4,Advances in cell biology, molecular biology, and genetics over the ensuing years began to help explain the mechanisms of endocrine diseases a

5、nd of hormone secretion and action. Although these advances have embedded endocrinology into the framework of molecular cell biology, they have not changed the essential subject of endocrinology _the signaling that coordinates and controls the functions of multiple organs and processes.,History and

6、development of Endocrinology (2),5,Hormone formation may occur either in localized collections of specific cells, in the endocrine glands, or in cells that have additional roles. Many protein hormones: growth hormone? parathyroid hormone? prolactin? insulin? glucagon? Leptin? Formation of small horm

7、one molecules initiates with commonly found Precursors: Such as: adrenals, gonads, or thyroid. In the case of the steroid hormones, the precursor is cholesterol, which is modified by various hydroxylations, methylations, and demethylations to form the glucocorticoids, androgens, and estrogens. In co

8、ntrast, the precursor of vitamin D, 7-dehydrocholesterol, is produced in skin keratinocytes, again from cholesterol, by a photochemical reaction.,ENDOCRINE GLANDS,6,内分泌系统,内分泌腺,脏器内分泌组织,激素 体液调节系统（包括旁分泌、自分泌）,代谢过程,脏器功能,生长发育,生殖衰老,Endocrine System,7,内分泌学发展三阶段,腺体内分泌学 Organic Endocrinology 组织内分泌学 Histologic

9、al Endocrinology 分子内分泌学 Moleculer Endocrinology,8,激素的种类 Hormones,肽类/蛋白类激素 （Protein or peptide) : ACTH,LH, FSH, PHT, TSH, Insulun ,Glucagon, IGFs 氨基酸衍生物（Amino Acid derivatives)： 儿茶酚胺类（肾上腺素、去甲肾上腺素） 脂肪酸衍生物(Fatty acid derivatives ): 前列腺素类、视黄酸 胆固醇衍生物（Cholesterol derivatives )： 考的松， 醛固酮、1,25(OH)2 D3性激素,9,

10、激素的作用机制（1）,与膜受体结合 G蛋白偶联 发挥生物效应,（肽类激素、生物胺、前列腺素）,与膜受体结合 受体自身磷酸化 发挥生物学效应 （酪氨酸激酶） （生长因子家族、Insulin , IGFs),与核受体结合 与DNA特异序列结合 功能蛋白转录 （甾体类激素）,10,11,G-protein-coupled 7-membrane spanning receptor,12,G-protein-coupled 7-membrane spanning receptor,13,14,15,16,激素的作用机制（2）,激素信息在细胞内的信号传导,Coris: 发现了磷酸化酶的可逆磷酸化 （无活性

11、的磷酸化酶b/有活性的磷酸化酶a之间的互变） 获得1951年诺贝尔奖。 Sutherland: 成功分离和确定的腺苷酸环化酶和磷酸二酯酶 （cAMP合成与分解的两个关键酶） 提出了激素作用的第二信使学说 获得1971年诺贝尔生理医学奖。 Krebs a high blood glucose level discovered in a shopping mall kiosk. The very absence of symptoms lends an unreality to the moment and should become an explicit topic of the patien

12、t-doctor interaction. In this circumstance, it is worth emphasizing the value of early discovery and prevention of greater morbidity.,SPECIAL FEATURES OF ENDOCRINE ILLNESS,32,The symptoms of endocrine disorders overlap a great range of normal characteristics, including: body contour, facial configur

13、ations, weight distributions, skin and hair coloring, and muscular capacity. They also overlap with other conditions that are far more common, including: depression and normal aging. The added adipose tissue of hyperadrenocorticism is more difficult to recognize in a person who is already obese. The

14、 nervousness associated with hyperthyroidism is less apparent in a thin, hyperkinetic man than in a person of moderate body weight. The effects of an androgen-producing adrenal tumor are less likely to be noticed in a family of swarthy, hirsute individuals.,Overlap with Other Diseases (1),33,Overlap

15、 with Other Diseases (2),Finally, most endocrine disorders evolve gradually over months to years instead of appearing suddenly,. This combination of varied host background and slow evolution of disease leads to considerable delay in diagnosis: both the patient and primary care physician adapt to the

16、 changes as part of the person, and definitive evaluation, now relatively easy for most disorders, is not undertaken. Hypothyroidism and acromegaly are good examples of this phenomenon. All series show a remarkable delay in diagnosis despite sometimes disabling symptoms.,34,Overlap with Other Diseas

17、es (3),Hormones have more distant effects than local effects. This, of course, reflects their messenger status. Unlike an abscess, a myocardial infarction, or an esophageal cancer, endocrine disorders seldom produce symptoms near the gland of origin. (Subacute thyroiditis and large pituitary tumors,

18、 of course, are exceptions.) But because in most endocrinopathies the excess or missing hormone works on several or many systems, the resulting syndrome can be enigmatic.,35,Overlap with Other Diseases (4),Several endocrine disorders are important not because of their incidence but because of their curability: Cus