1、1,內(nèi)分泌系統(tǒng)疾病總 論Introduction to Endocrinology and Metabolic Diseases,復(fù)旦大學(xué)附屬中山醫(yī)院內(nèi)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,內(nèi)分泌系統(tǒng),內(nèi)分泌腺,臟器內(nèi)分泌組織,激素 體液調(diào)節(jié)系統(tǒng)（包括旁分泌、自分泌）,代謝過程,臟器功能,生長(zhǎng)發(fā)育,生殖衰老,Endocrine System,7,內(nèi)分泌學(xué)發(fā)展三階段,腺體內(nèi)分泌學(xué) Organic Endocrinology 組織內(nèi)分泌學(xué) Histologic

9、al Endocrinology 分子內(nèi)分泌學(xué) Moleculer Endocrinology,8,激素的種類 Hormones,肽類/蛋白類激素 （Protein or peptide) : ACTH,LH, FSH, PHT, TSH, Insulun ,Glucagon, IGFs 氨基酸衍生物（Amino Acid derivatives)： 兒茶酚胺類（腎上腺素、去甲腎上腺素） 脂肪酸衍生物(Fatty acid derivatives ): 前列腺素類、視黃酸 膽固醇衍生物（Cholesterol derivatives )： 考的松， 醛固酮、1,25(OH)2 D3性激素,9,

10、激素的作用機(jī)制（1）,與膜受體結(jié)合 G蛋白偶聯(lián) 發(fā)揮生物效應(yīng),（肽類激素、生物胺、前列腺素）,與膜受體結(jié)合 受體自身磷酸化 發(fā)揮生物學(xué)效應(yīng) （酪氨酸激酶） （生長(zhǎng)因子家族、Insulin , IGFs),與核受體結(jié)合 與DNA特異序列結(jié)合 功能蛋白轉(zhuǎn)錄 （甾體類激素）,10,11,G-protein-coupled 7-membrane spanning receptor,12,G-protein-coupled 7-membrane spanning receptor,13,14,15,16,激素的作用機(jī)制（2）,激素信息在細(xì)胞內(nèi)的信號(hào)傳導(dǎo),Coris: 發(fā)現(xiàn)了磷酸化酶的可逆磷酸化 （無(wú)活性

11、的磷酸化酶b/有活性的磷酸化酶a之間的互變） 獲得1951年諾貝爾獎(jiǎng)。 Sutherland: 成功分離和確定的腺苷酸環(huán)化酶和磷酸二酯酶 （cAMP合成與分解的兩個(gè)關(guān)鍵酶） 提出了激素作用的第二信使學(xué)說 獲得1971年諾貝爾生理醫(yī)學(xué)獎(jiǎng)。 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