Endocrine System - PDF 免费下载

Nervous & Endocrine Systems 4

Physiological Properties of Hormones Small amounts (pg~μg) The secretion rate is determined by the need No effect on the source Act on soma or target organs As trigger substances May have many effects e.g. oxytocin 5

Circulating & Local Hormones 6

Categories of Hormones 7

依化學組成 : Categories of Hormones 1. Amine Hormones: Adrenal medulla -NE EP (CAs) Thyroid gland -Thyroxine (T 4 ) 2. Peptide hormones -Prolactin Growth hormone. 3. Steroid hormones: Adrenal cortex -Cortisol Aldosterone Sex hormones -Estrogens Progesterone Androgens 9

Polypepetide & Glycoproteins Hormones 激素結構腺體主要的效果抗利尿激素 (Antidiuretic hormone) 8 個胺基酸腦下腺後葉水份保留和血管收縮催產素 (Oxytocin) 8 個胺基酸腦下腺後葉子宮和乳腺的收縮胰島素 (Insulin) 昇糖激素 (Glucagon) 腎上腺皮促素 (ACTH) 副甲狀腺素 (Parathyroid hormone) 濾泡刺激素 (FSH) 黃體刺激素 (LH) 甲狀腺刺激素 (TSH) 21 和 30 個胺基酸 ( 雙鍵 ) 蘭氏小島的 β 細胞 29 個胺基酸蘭氏小島的 α 細胞細胞的葡萄糖吸收脂肪合成作用和肝糖合成作用水解所儲存的肝糖和脂肪 39 個胺基酸腦下腺前葉刺激腎上腺皮質 84 個胺基酸副甲狀腺增加血鈣的濃度醣蛋白腦下腺前葉刺激目標腺體的成長發育和分泌 10

Biosynthesis and Secretion of Pepetide Hormones pre-pro-insulin pro-insulin insulin 11

Preprohormones & Prohormones 活化型激素的先趨物 - 稱為前激素 (prohormones) 前原激素 (preprohormones) 前激素在內分泌細胞中是不活化的先趨分子前原激素是內分泌腺體平常分泌的分子, 為了使其成為活化態, 必須在標的細胞中轉換成其它的衍生物 12

Biosynthesis of Steroid Hormones 13

Biosynthesis of Steroid Hormones 14

Categories of Hormones 依接受器所在位置 : Types Major From in Plasma Location of Receptors Signal Transduction Mechanisms Rate of Excretion/ Metabolism Peptides and catecholamines (Water-Soluble Hormones) Free Plasma membrane 1. Second messenger 2. Enz activation by receptor (JAK kinase): 3. Intrinsic enz activity of receptor (tyrosine kinase) Fast (minutes) Steroids and thyroid hormones Proteinbound Cell interior Intracellular receptors directly alter gene transcription Slow (hours to days) (Lipid-Soluble Hormones) 15

Action of Water- Soluble Hormones 16

Tyrosine kinase 18

Action of Lipid- Soluble Hormones 19

Nuclear Receptors 1. Steroid hormones: Adrenal cortex -Cortisol Aldosterone Sex hormones -Estrogens Progesterone Androgens 2. Sterols -vitamin D 3. Thyroid hormone 4. Retinoic acid( 視網酸 ) 20

General Mechanisms of Hormone Action Hormone binds to cell surface or receptor inside target cell Cell may then --synthesize new molecules --change permeability of membrane --alter rates of reactions Each target cell responds to hormone differently --At liver cells---insulin stimulates glycogen synthesis --At adipocytes---insulin stimulates triglyceride synthesis Synthetic drugs may block receptors for naturally occurring hormones --Normally, progesterone levels drop once/month leading to menstruation. Progesterone levels are maintained when a woman becomes pregnant. --RU486 (mifepristone) binds to the receptors for progesterone preventing progesterone from sustaining the endometrium in a pregnant woman brings on menstrual cycle used to induce abortion Misoprostol (Cytotec) 22

Hormone Metabolism and Excretion 23

Control of Hormones Secretion Negative Feedback Control 1. Ions or Nutrients 2. NTs of neurons 3. Other hormones: tropic hormones 24

Hypothalamus 位於腦部的 pituitary gland 上方,hypothalamus 與 pituitary gland 以垂體門脈系統的血管聯繫 :hypothalamus 與 pituitary gland 的前葉聯繫, 前葉又稱腺垂體 (anterior lobe;adenohypophysis), 是靠血管來聯繫 ; 若是在後葉又稱神經垂體 (posterior lobe;neurohypophysis), 則是靠神經來聯繫下視丘是由許多神經核, 也就是許多神經細胞所組成在神經末梢中突 (median eminence) 停止, 當神經末梢釋放出激素 ( 下視丘所分泌 ), 也就是 releasing factor 則釋放出來後會被微血管吸收, 則這地方稱為門脈系統, 會透過血液循環跑到 pituitary gland 前葉, 而其前葉有許多細胞, 而細胞上有許多接受器, 一結合, 就會分泌出激素 2 (trophic hormones ) 是由 pituitary gland 所分泌下視丘 hormones 分泌呈現脈動型 (pulsatile pattern) 且受到許多因素影響如日照四季變化情緒等下視丘所分泌釋放的激素是以其所調控的腦下腺激素來命名如甲釋素 (thyrotropin-releasing hormone;trh) 去刺激腦下腺甲狀腺刺激素 (thyrotropin 或 thyroid-stimulating hormone,tsh) 的合成及分泌 25

Pituitary Gland 位於腦部底層的蝶鞍 (sella turcia) 中, 以腦下垂体柄 (pituitary stalk) 或漏斗 (infundibulum) 懸起來, 所以下視丘與腦下垂体靠 pituitary stalk 來相連接起來在 pituitary stalk 中有垂体門脈系統, 因此下視丘藉著血管系統將其激素送到 pituitary stalk 產生作用而去分泌胚胎再發育時, 由咽喉向腦部形成一個突起稱為雷氏曩 (Rathke s pouch) 而腦中第三腦室的部分組織也向咽喉部延伸與雷氏曩合併而形成腦下垂体, 其中由雷氏曩所形成的部分稱之為腺垂體 (adenohypohysis) 由第三腦室所形成的部分稱之神經垂体 (neurohypophysis) 腦下垂体可分為三部份 :1. 腦下腺前葉 (anterior lobe) 由雷氏曩形成, 又稱 adenohypohysis 2. 中葉是前葉與後葉接合部份 3. 腦下腺後葉 (posterior lobe) 由第三腦室形成, 又稱 neurohypophysis 26

Hypothalamus & Pituitary Gland Hypothalamo-Hypophyseal Portal System Hypothalamo-Hypophyseal Tract 27

A typical 3-hormone sequence of hormone control 28

Hypothalamic Hormones 29

Anterior Pituitary Hormones 30

下視丘激素腦下腺前葉影響腦下腺前葉激素作用皮釋素 (CRH;corticotropin releasing hormone) 性釋素 (GnRH;gonadotropin releasing hormone) 泌乳激素抑制激素 (PIH;prolactin inhibiting hormone ; PIF:dopamine ) 體制素 (SS;somatostatin) 甲釋素 (TRH;thyrotropin releasing hormone) 生長素釋素 (GHRH;growth hormone releasing hormone) 刺激腎上腺皮促素 (ACTH) 的分泌刺激濾泡刺激素 (FSH) 和黃體刺激素 (LH) 的分泌抑制泌乳激素 (PRL) 的分泌抑制生長激素 (GH) 和甲狀腺激素 (TSH) 的分泌刺激 TSH 的分泌刺激生長激素 (GH) 的分泌刺激腎上腺皮質的分泌刺激性腺產生配子和性類固醇的分泌刺激乳腺產生乳汁刺激許多器官的同化代謝和成長刺激甲狀腺素的分泌刺激許多器官的同化代謝和成長 32

Anterior Pituitary Gland (Adenohypophysis) The blood supply to the anterior pituitary is from the superior hypophyseal arteries. Hormones of the anterior pituitary and the cells that produce the: Human growth hormone (hgh) is secreted by somatotrophs. Thyroid-stimulating hormone (TSH) is secreted by thyrotrophs. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by gonadotrophs. Prolactin (PRL) is secreted by lactrotrophs. Adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating hormone (MSH) are secreted by corticotrophs. 33

腦下腺前葉激素作用地方激素刺激調節方法腎上腺皮促素 [ACTH] 腎上腺皮質分泌糖皮質激素被 CRH 刺激 ; 被 (adrenocorticotropic hormone) (adrenal cortex) (glucocorticoids) glucocoticoids 抑制甲狀腺激素 [TSH] (thyroid stimulating hormone) 甲狀腺 (thyroid gland) 分泌甲狀腺素 (thyroid hormones) 被 TRH 刺激及 thyroid hor. 所抑制生長激素 [GH] 大多數組織脂肪分解會增加被 SS 所抑制 ; 被 (growth hormone; somatotropic hormone ) ( 沒有專一性 ) 增加血糖 protein 合成增加 GHRH 所刺激濾泡刺激素 [FSH] (follicle stimulating hormone) 性腺 (gonads) 配子 (gametes) 精子和卵子產生性類固醇分泌被 GnRH 所刺激 ; 被性類固醇抑制黃体刺激素 [LH] 性腺性激素分泌排卵被 GnRH 所刺激 (luteinizing hormone) 黃体形成泌乳激素 [PRL] (prolactin) 乳腺乳汁的產生被 PIH=PIF 抑制 34

Pro-opio-melanocortin (POMC): MSH ACTH endophrine 36

Posterior Pituitary Gland (Neurohypophysis) Although the posterior pituitary gland does not synthesize hormones, it does store and release two hormones. Hormones made by the hypothalamus and stored in the posterior pituitary are oxytocin (OT) and antidiuretic hormone (ADH). The neural connection between the hypothalamus and the neurohypophysis is via the hypothalamo-hypophyseal tract. 37

腦下腺後葉激素作用地方生理作用調節方法抗利尿激素 [ADH ; AVP ] (antidiuretic hormone ; vasopressin) 腎小管及血管排尿血壓受滲透度增加而刺激催產素 [OX] (oxytocin) 子宮及乳腺促使子宮肌肉收縮具有催產或引產的作用乳腺分泌乳汁生產時子宮被興奮, 會引起催產素分泌會增加陰道刺激時, 會引起催產素分泌會增加哺乳時刺激乳頭, 會引起催產素分泌會增加 38

Types of Endocrine Disorders I. Endocrine disorders may be classified as hyposecretion, hypersecretion, and target-cell hyporesponsiveness or hyperresponsiveness. a. Primary disorders are those in which the defect is in the cells that secrete the hormone. b. Secondary disorders are those in which there is too much or too little tropic hormone. c. Hyporesponsiveness is due to an alteration in the receptors for the hormone, to disordered postreceptor events, or to failure of normal metabolic activation of the hormone in those cases requiring such activation. II. These disorders can be distinguished by measurements of the hormone and any tropic hormones under both basal conditions and during experimental stimulation of the hormone s secretion. 42

hgh & IGF Insulin-like Growth Factors 43

Regulation of hgh Low blood sugar stimulates release of GHRH from hypothalamus --anterior pituitary releases more hgh, more glycogen broken down into glucose by liver cells (diabetogenic effect) High blood sugar stimulates release of GHIH (SS) from hypothalamus --less hgh from anterior pituitary, glycogen does not breakdown into glucose 44

GH Laron Dwarf [GH] normal GH-R defects 45

紅孩症 ( 紅嬰症惡性營養不良症 ) 誇希奧科病 somatomedin 46

GH 47

ACTH 48

osmolality 49

ADH 50

Thyroid Gland 52

Histology of Thyroid Gland Follicle = sac of stored hormone (colloid) surrounded by follicle cells that produced it--t3 & T4 Inactive cells are short In between cells called parafollicular cells--produce calcitonin 53

Thyroid Hormone 特性 T4 T3 I 的數目 ( 位置 ) 4 個 (3,5,3,5 ) 3 個 (3,5,3 ) 生合成 DIT+DIT MIT (monoiodide tyrosine; 一個碘的酪胺酸 ) +DIT( 兩個碘的酪胺酸 ) 生物活性 1 倍 4~5 倍 Half-life( 半衰期 ) A week A day 血中濃度 99.6% 0.35% Free form 0.1 1 Binding affinity with TBG 10 倍 1 倍 TBG (thyroxine-binding globulin) T4 > T3 TBPA (thyroxine-binding prealbumin) T4 > T3 Albumin T4 < T3 54

Thyroid Hormone 55

Synthesis of Thyroid Hormone TGB (tyrosine residue) + Iodide 56

Synthesis of Thyroid Hormone (Iodide trapping) 57

Synthesis of Thyroid Hormone 58

Secretion of Thyroid Hormone 59

Secretion of Thyroid Hormone Thyroid 4 2 80 T3 31 μg (3,5,3 ) Active T4 27 36 5 -deiodinase 80 μg 17 5-deiodinase RT3 38 μg (3,3,5 ) Inactive Conjugates, etc 60

Function of Thyroid Hormone 生熱作用 (calorigenesis) 其身體 Metabolic rate, 且加速醣類的分解作用以及葡萄糖的新生 ( 利用 glucose 來產生能量 ) 營養的代謝可增加腸胃道對醣類的吸收速率肌肉功能的影響其可增加心肌及骨骼肌的收縮能力, 所以當 T 4 and T 3 濃度, 會產生肌肉顫抖神經系統的影響可提高思考速率及敏感度, 但過多會造成神經質焦慮或妄想等精神異常現象 ; 若不足則會造成思想過慢及警覺性降低等症狀呼吸系統的影響可增加呼吸頻率 ( 換氣 ) 及深度, 這是因為 Metabolic rate 造成 O 2 consumption 及 CO 2 的生成增加所引起其他一般而言, 過多的 thyroid hormone 會造成體重下降 ; 過少則體重會增加血流及心輸出量也因代謝速率提高而增加 64

Endemic Goiter Disorders T3/T4 TSH TRH Thyroid gland Anterior pituitary Hypothalamus 65

甲狀腺機能低下症 (hypothyroidism) ( 黏液水腫 ) ( 呆小症 ) 66

甲狀腺機能亢進症 (Hyperthyroidism) 葛瑞夫氏症 (Grave s disease) 凸眼症 (exophthalmos) 67

Parathyroid Gland (Chief cells) 68

Histology of Parathyroid Gland The parathyroid glands are embedded on the posterior surfaces of the lateral lobes of the thyroid principal cells produce parathyroid hormone oxyphil cells function is unknown. Parathyroid hormone (PTH) regulates the homeostasis of calcium and phosphate increase blood calcium level decrease blood phosphate level increases the number and activity of osteoclasts increases the rate of Ca+2 and Mg+2 from reabsorption from urine and inhibits the reabsorption of HPO4-2 so more is secreted in the urine promotes formation of calcitriol(vitd3), which increases the absorption of Ca+2, Mg+2,and HPO4-2 from the GI tract 69

Parathyroid Hormone 70

Parathyroid Hormone 71

Synthesis of 1,25-(OH) 2 Vit D 3 軟骨症佝僂病 PTH 72

(Ergocalciferol) (Cholecalciferol) 1,25-(OH) 2 D 73

Calcitonin 74

Calcium Balance 75

Regulation of Calcium Blood Levels 77

Regulation of Calcium Blood Levels 78

Regulation of Calcium Blood Levels 79

副甲狀腺機能症 (hypoparathyroidism) 80

副甲狀腺機能亢進症 (hyperparathyroidism) 81

Adrenal Gland The adrenal glands are located superior to the kidneys 3 x 3 x 1 cm in size and weighs 5 grams consists of an outer cortex and an inner medulla. Cortex produces 3 different types of hormones from 3 zones of cortex Medulla produces epinephrine & norepinephrine 82

Adrenal Cortex 83

Adrenal Gland Hormones 名稱腎上腺皮質 (adrenal cortex) 腎上腺髓質 (adrenal medulla) 特性 1. 分泌 corticosteroid( 皮質類固醇 ), 來自胚胎的中胚層, 佔 adrenal gland 的 80~90 % 2. 分為三層 : 絲 ( 球 ) 狀帶 (zona glomerulosa):aldosterone 分泌 mineralcorticoids ( 礦物質皮質類固醇 ) 佔 15 % 束狀帶 (zona fasciculata):cortisol 分泌 glucocorticoids ( 糖質皮質類固醇 ) 佔 25 % 網狀帶 (zona reticularis):androgens & estrogens 分泌性類固醇 (sex steroids) 佔 60 % 分泌 catecholamine, EP:NE 分泌比例 4:1, 來自胚胎的外胚層, 佔 adrenal gland 的 10~20 % 84

Adrenal Gland Hormones ( 嗜鉻細胞 ) 85

Synthesis of Adrenal Gland Hormones 86

Functions of Adrenal Cortex Hormones 激素名稱 Aldosterone Cortisol Androgens & estrogens 功能 1. 增加腎臟對 Na + 及水的再吸收 2. 增加腎臟對 K + 及 H + 的排出 3. 血管收縮 1. 糖質新生作用 (blood sugar ) 2. 抑制骨骼合成, 抑制 Vit D 的生成及作用 3. 增加腎臟血流量, 同時抑制 ADH 的作用 ( 多尿 ) 4. 抗發炎及抗過敏作用 5. 抑制免疫反應.. 增加第二性徵發育.. 87

Functions of Cortisol increase rate of protein catabolism & lipolysis conversion of amino acids to glucose stimulate lipolysis provide resistance to stress by making nutrients available for ATP production raise BP by vasoconstriction anti-inflammatory effects reduced (skin cream) reduce release of histamine from mast cells decrease capillary permeability depress phagocytosis 88

Regulation of Aldosterone Renin-Angiotensin-Aldosterone system (RAA system) 89

Stimuli Blood pressure Blood flow to kidney Juxtaglomerular apparatus in kidney Angiotensinogen Renin Angiotensin II Angiotensin I Converting enzyme Hypothalamus Aldosterone Thirst Salt and water retention by kidney Vasoconstriction of arterioles Negative feedback Blood volume response Blood pressure 90

(Primary Adrenal Insufficiency) 91

General Adaptation Syndrome 94

Pheochromocytoma 腎上腺髓質的腫瘤是指嗜鉻性細胞瘤 (Pheochromocytoma) 這腫瘤造成腎上腺素和正腎上腺素過量的分泌, 其產生的結果類似交感神經系統連續的刺激這症狀包括代謝率升高高血糖尿糖神經質消化系統問題和出汗在這情況下, 並不會花太久的時間就變成全身性疲勞, 造成病人易感染其他疾病 95

Anatomy of Pancreas Cells (99%) in acini produce digestive enzymes Endocrine cells in pancreatic islets produce hormones 96

Pancreatic Islet (Islet of Langerhans ) Cell types 特性 A cell (αcell ) 分泌 Glucagon (29 aa); 約佔 20~25 % B cell (βcell ) 分泌 Insulin (51 aa); 約佔 60~70 % D cell (δcell ) 分泌 SS; 約佔 10 % F cell 分泌 pancreatic polypeptide 97

Pancreatic Islet Hormones 98

Pancreatic Islet Hormones 99

Taget-cell Responses of Insulin Insulin presence (storage) Insulin absence (mobilization) 酮体 (ketone body ):Acetone,Acetoacetate,β-hydroxybutyrate 100

101

Insulin Action (GLUT-4) muscle cells and adipose tissue cells 102

Regulation of Insulin Secretion 禁食 (65-105 mg/dl) 進食 (140-150 mg/dl) Sulfonylurea therapy K ATP channel 103

Regulation of Insulin Secretion 104

Insulin/Glucagon Secretion: Blood Glucose 105

Insulin/Glucagon Secretion: Fasting 106

Regulation of Insulin/Glucagon Secretion 107

Metabolic Effects of Hormones 108

Metabolic Effects of Hormones 109

Metabolic Effects of Cortisol 110

Metabolic Effects of EP/Sym Nerves G pt/ac/camp 111

特性 Diabetes Mellitus 依賴型 ( 第一型 ) IDDM 非依賴型 ( 第二型 ) NIDDM 發生年紀 <20 歲 ( 幼發型 DM) >40 歲 ( 成年型 DM) 症狀發生快慢發生酮酸症經常很少小島的 β 細胞 ( 疾病初期 ) 受損健全對抗小島細胞的自身免疫抗體治療 Syphon 有注射胰島素 Honey 所佔比率 10% 90% 和肥胖有關很少經常胰島素分泌減少正常或增加無飲食運動口服降血糖藥 (sulfonylureas) 112

IDDM NIDDM 113

Diabetic Ketoacidosis IDDM Excessive urine production (polyuria) Excessive thirst (polydipsia) Excessive eating (polyphagia) 114

Pineal Gland Small gland attached to 3rd ventricle of brain Consists of pinealocytes & neuroglia Melatonin responsible for setting of biological clock Jet lag & Seasonal Affective Disorder (SAD) treatment is bright light 115

Effect of Light on Pineal Gland Melatonin secretion producing sleepiness occurs during darkness due to sti. of SCN activity 116

生活可以很多角度有位老師進了教室, 在白板上點了一個黑點他問班上的學生說這是什麼? 大家都異口同聲說一個黑點老師故作驚訝的說只有一個黑點嗎? 這麼大的白板大家都沒有看見? 試想你看到的是什麼? 每個人身上都有一些缺點, 但是你看到的是那些呢? 是否只有看到別人身上的 " 黑點 " 卻忽略了他擁有了一大片的白板 ( 優點 )? 其實每個人必定都有許多的優點, 換一個角度去看吧!! 你會有更多新的發現 117