The Pituitary Gland( 垂体 )

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1 The Pituitary Gland( 垂体 )

2 Pituitary Gland Adenohypophysis (anterior pituitary, 腺垂体 ) Neurohypophysis(posterior pituitary, 神经垂体 )

3 Structure of the Pituitary Gland Two distinct lobes Anterior pituitary (Adenohypophysis) true endocrine tissue secretes classic hormones Posterior pituitary (Neurohypophysis) neural tissue secretes neurohormones( 神经激素 )

4 Adenohypophysis( 腺垂体 ) Hormones:7 Growth hormone(gh, 生长激素 ) Prolactin(PRL, 催乳素 ) Thyroid-stimulating hormone(tsh, 促甲状腺激素 ) Adrenocorticotropic hormone(acth, 促肾上腺皮质激素 ) Gonadotropin( 促性腺激素 ) Follicle-stimulating hormone(fsh, 促卵泡激素 ) Luteinizing hormone(lh, 黄体生成素 ) Melanocyte-stimulating hormone(msh, 促黑激素 )

5 Targets and major functions of the 6 classical anterior pituitary hormones

7 Growth Hormone (GH) Human growth hormone (hgh) Somatotropin( 躯体刺激素 ) Protein 191 amino acids About 22,000 (22k)

8 Growth Hormone Homologous with prolactin and human placenta lactogen (hpl, 催乳激素 )

Diurnal rhythm GH secretion occurs in episodic bursts and exhibits diurnal rhythm( 日周期节律 ) During most of the day, little or no GH is secreted, although bursts can be elicited

9 Diurnal rhythm GH secretion occurs in episodic bursts and exhibits diurnal rhythm( 日周期节律 ) During most of the day, little or no GH is secreted, although bursts can be elicited by certain stimuli such as stress( 应激 ), hypoglycaemia( 低血糖 ), and exercise In 1 to 2 hours after a person falls asleep, one or larger, prolonged bursts of secretion may occur

Growth Hormone Net effect is: GH secretion is highest during adolescence, next highest in children and lowest in adults The decreased GH secretion associated with

10 Growth Hormone Net effect is: GH secretion is highest during adolescence, next highest in children and lowest in adults The decreased GH secretion associated with aging is responsible, in part, for the decrease in lean body and bone mass, the expansion of adipose tissue, and the thinning of the skin that occur as people age

11 Growth Hormone Physiologic functions The most striking and specific effect: growth Stimulates cartilage( 软骨 ) and bone growth Most important for postnatal growth e.g. promote bone lengthening by stimulating maturation and cell division of the chondrocytes( 软骨细胞 ) in the epiphyseal plate Stimulates growth of visceral organs ( 内脏器官 ) Epiphyseal- a part of a long bone where bone growth occurs from

12 Growth Hormone Physiologic functions GH needs a mediator for its growth-promoting action

13 Growth rate in boys and girls During pubertal development, GH collaborates with thyroid hormones, insulin, gonadal hormones and cortisol (permissive effect) to maximize growth potential

Ketogenic increase lipolysis( 脂肪分解 ) increase fatty acid oxidation ketones( 酮 )

14 Growth Hormone Physiologic functions Metabolic Effects Anabolic increase amino acid uptake, protein, RNA/DNA synthesis decrease amino acid/protein degradation Ketogenic increase lipolysis( 脂肪分解 ) increase fatty acid oxidation ketones( 酮 ) Diabetogenic increase plasma glucose ( uptake & gluconeogenesis, 糖异生 ) increase insulin secretion

15 Information GH supplement for children or adults with normal growth may result in the development of Diabetes( 糖尿病 ) Abnormal growth of bones and internal organs (heart, kidneys, and liver) Atherosclerosis( 动脉硬化 ) Hypertension( 高血压 )

16 Growth Hormone Regulation of GH secretion Hypothalamus GHRH and somatostatin (SS) Negative feedback control GH and IGF-I

17 In addition to the hypothalamus, a number of hormones (sex hormones, insulin and TH) influence the secretion of GH Growth Hormone

Growth Hormone Abnormalities of GH secretion Dwarfism( 侏儒症 ) Deficiency of GH during childhood A hereditary inability to form IGF-1 Gigantism( 巨人症

19 Growth Hormone Abnormalities of GH secretion Dwarfism( 侏儒症 ) Deficiency of GH during childhood A hereditary inability to form IGF-1 Gigantism( 巨人症 pituitary giant ) Over-production of GH by the pituitary gland in a child Excessive long bone growth Usually caused by tumors in the ant. Pituitary gland

20 Growth Hormone Abnormalities of GH secretion Acromegaly( 肢端肥大症 ) caused by tumors in the ant. Pituitary gland after puberty GH results in thickening of many bones in the body, most noticeably in the hands, feet and head and metabolic derangement Many internal organs notably the heart also become enlarged and this can interfere with their ability to function normally

21 Growth Hormone Abnormalities of GH secretion Acromegaly The jaw enlarges to give the characteristic facial appearance (prognathism, 凸颌 ) acromegaly is also associated with elevated plasma levels of glucose and fatty acids, similar to the level of diabetes

22 Growth Hormone Abnormalities of GH secretion Treatment of gigantism and acromegaly surgical removal of the pituitary tumor long-acting analogs of somatostatin

23 Prolactin( 催乳素 ) Protein 207 AA Function

24 Prolactin Regulation: Prolactin-releasing factor(prf) Prolactin-release inhibiting hormone (PIF)

25 Melanocyte-stimulating hormone (MSH) Types α-,β-and γ-msh Synthesis Precursor: POMC ( 阿黑皮素原 )

26 Melanocyte-stimulating hormone (MSH) Primary effect Disperse the melanin( 黑色素 ) granules in melanophores( 黑色素细胞 ) Regulation MIF: (-)MSH MRF : (+)MSH

29 Posterior Pituitary Hormones Synthesized by cell bodies in hypothalamus Transported to posterior pituitary in axoplasm( 轴浆 ) of the neuron s fibers Hormones: ADH or vasopressin (supraoptic nuclei, 视上核 ) Oxytocin (paraventricular nuclei, 室旁核 )

30 Posterior Pituitary Hormones Antidiuretic hormone (ADH, 抗利尿激素 ) or Vasopressin(VP, 血管升压素 ) Oxytocin (OXT, 催产素 )

Actions of Antidiuretic Hormone (ADH) Water retention Target organ: ADH-sensitive cells in distal tubules & collecting ducts of renal medulla ADH binds to V2 receptors Enhances permeability of

31 Actions of Antidiuretic Hormone (ADH) Water retention Target organ: ADH-sensitive cells in distal tubules & collecting ducts of renal medulla ADH binds to V2 receptors Enhances permeability of cell membrane to water Increase vascular tone Target organ: arteriolar( 小动脉 ) smooth muscle cells ADH binds to V1 receptors Vasoconstriction Therefore ADH is also named Arginine Vasopressin (AVP)

32 Antidiuretic hormone (ADH) -Vasopressin(VP) Regulation osmolality ADH blood volume ADH (atrial receptors)

33 Oxytocin (OXT) Secretion Parturition, lactation and coition OXT Action of OXT Contraction of the uterus induces labor contraction reduces postpartum bleeding( 产后出血 ) Contraction of myoepithelial cells in the breast stimulates milk let-down

34 Oxytocin

35 Thyroid Gland( 甲状腺 ) Thyroid gland becomes functional early in fetal life as it plays a role in the development of brain cells (forming nerve terminals/ synapse/ dendrites/ myelin)

36 Thyroid Gland Thyroid follicles( 腺泡 ) are sacs lined with follicular cells and containing thyroglobulin ( 甲状腺球蛋白 )called colloid. The follicular cells take part in almost all stages of TH synthesis and Secretion

37 Thyroid Hormones( 甲状腺激素 ) Types 90% of metabolically active hormones secreted by thyroid is thyroxine (T4, 四碘甲腺原氨酸 ), 10% is triiodothyronine (T3, 三碘甲腺原氨酸 ), and less than 1% is rt3 Iodide is required (1mg/week) for thyroid hormone synthesis

38 Thyroid Hormones Thyroxine (T 4, 甲状腺素 ) Major hormone released from thyroid follicles Contains 4 iodine atoms More abundant than T 3 Synthesis occurs in follicular cell colloid via the combination of DIT + DIT

potent than T 4 (T 3 = 5 T 4 ) Contains 3 iodine atoms Synthesis

39 Thyroid Hormones Triiodothyronine (T 3 ) Generally formed from T4 by cleaving an iodine molecule (deiodinase ( 脱碘酶 )in target cells) More potent than T 4 (T 3 = 5 T 4 ) Contains 3 iodine atoms Synthesis occurs in the follicular cell colloid via the combination of DIT + MIT

40 Thyroid Hormones Synthesis Materials Iodine (in the form of iodide I - ) 50mg/year Iodized table salt (1 sodium iodide/100,000 NaCl) Tyrosine Thyroglobulin (TG) 70 tyrosines

41 Thyroid Hormones Biosynthesis Iodine/iodide trapping( 聚碘 ) Iodide pump( 碘泵 ) Oxidation of iodide Peroxidase( 过氧化酶 ): I - I 0 or I 3 -

42 Thyroid Hormones Biosynthesis Iodination of tyrosine Peroxidase MIT and DIT Formation of T3, T4 by coupling

43 Thyroid Hormones

44 Thyroid Hormones Storage In the follicles In the form of TG For 2 ~3 months Release TSH Proteinase(lysosome)

Thyroid Hormones Transport Most T 4 and T 3 bound to plasma proteins synthesized by liver(99%) Thyroxine-binding globulin(tbg, 甲状腺素结合球蛋白 ): mainly Thyroxine-binding prealbumin Albumin Slowly

45 Thyroid Hormones Transport Most T 4 and T 3 bound to plasma proteins synthesized by liver(99%) Thyroxine-binding globulin(tbg, 甲状腺素结合球蛋白 ): mainly Thyroxine-binding prealbumin Albumin Slowly released to the tissue cells, slower for T 4 due to its higher affinity Slow onset and long duration of action Free(1%): T3 Concentration in plasma T 3 : 1.2 ~3.4 nmol/l T 4 : 85 ~142 nmol/l

46 Thyroid Hormones Physiological functions Effect on Growth Metabolism Nervous System Cardiovascular System GI Muscles, sexual function

47 Effects of TH on Growth Is essential for growth in children Promote bone formation and maturation Promote growth and development of brain (fetus and baby) Have synergistic effect with GH, IGF-1, insulin and other growth factors Tadpole frog

48 Effects of TH on Growth Cretinism( 呆小症或克汀病 ): deficiency of thyroid hormone during the period of fetal and early neonatal development short, stocky stature & mental retardation

+ -ATPase and active transport of ions (Na, K) heat

49 Metabolic Effects of TH Increase cellular metabolic activity number & activity of mitochondria ATP Na +, K + -ATPase and active transport of ions (Na, K) heat production O 2 consumption & BMR; CO 2 production ventilation

FFA + glycerol) Oxidation of free fatty acid serum cholesterol Protein metabolism Protein

50 Metabolic Effects of TH Carbohydrate metabolism glucose oxidation gluconeogenesis and glycogenolysis Too much blood glucose (Diabetes) Fat metabolism lipolysis (Triglyceride FFA + glycerol) Oxidation of free fatty acid serum cholesterol Protein metabolism Protein synthesis (normal) Protein catabolism (hyperthyroidism, 甲亢 ) Hypothyroidism( 甲低 ): myxedema( 粘液水肿 )

51 Effects of TH on Nervous System Important for maturation of CNS in perinatal period( 围产期 ) Enhance wakefulness, alertness, responsiveness to various stimuli Normal emotional tone also depend on proper thyroid hormone Increase the speed and amplitude of peripheral nerve reflexes Hyperthyroidism: hyperexcitability, insomnia, loss of concentration Hypothyroidism: mental retardation, sleepiness

52 Effects of TH on Cardiovascular System Increase blood flow and cardiac output metabolism utilization of O 2 & metabolic end products from tissue vasodilatation cardiac output ensures sufficient O 2 delivery to the tissues Increase heart rate (easy to detect!) increase adrenergic activity( response to adrenaline/noradrenaline) increase enzymatic activity Affect heart strength slightly increase of thyroid hormone increases heart strength marked increase of thyroid hormone decreases heart strength stroke volume + peripheral resistance pulse pressure

53 Effects of TH on GI Increase appetite and food intake Increase secretion of digestive juices Increase mobility of GI Diarrhea( 腹泻 ) often results from hyperthyroidism

54 Effects of TH On muscles hyperthyroidism muscle weakening (catabolic effect) fine muscle tremor is a characteristic sign for hyperthyroidism hypothyroidism muscles sluggish( 行动迟缓 ) On other endocrine glands secretion of insulin and cortisol On sexual function loss of libido( 性欲 ) Impotency( 性无能 ) abnormal menstruation( 月经 )

55 Thyroid Hormones Mechanisms of action Transcription of large numbers of genes Synthesis of great numbers of proteins

56 Regulation of TH secretion Hypothalmus-pituitary-thyroid axis TRH TSH T 3 /T 4 Negative feed-back of T 3 /T 4 Environmental factors cold, stress TRH Wolff-Chaikoff Effect autoregulation by I

57 Hypothalmus-pituitary-thyroid axis Hypothalamus TRH Tripeptide TSH secretion Cold: TRH release

58 Hypothalmus-pituitary-thyroid axis Pituitary TSH Glycoprotein T 3, T 4 synthesis and release Size of the thyroid cells camp mediated mechanism Hyperthyroidism thyroid stimulating immunoglobulin (TSI, 甲状腺刺激免疫球蛋白 )

59 Hypothalmus-pituitary-thyroid axis Thyroid Feedback effect of thyroid hormone T4 is converted into T3 in pituitary and T3 acts as the final effector to turn off TSH

60 Iodine-Deficient Goiter( 甲状腺肿 ) TSH is a trophic hormone, it stimulates not only T 3 /T 4 secretion but also protein synthesis in follicular cells. Therefore, exposure in thyroid size

61 Wolff-Charkoff effect Autoregulation by I low I intake stimulates synthesis of iodide trap high I intake (>2 mg/day) inhibits trap function and synthesis

62 Thyroid disorders Hyperthyroidism Hypothyroidism

63 Hyperthyroidism The most common cause B lymphocytes synthesize immune globulins (Ab called thyroid stimulating immunoglobulin, TSI) that bind to and active the TSH receptor, producing all the actions of TSH on thyroid (Graves disease).

64 Hyperthyroidism Clinical features enlarged thyroid (goitre) tachycardia ( HR, >100/ min, 心动过速 ) & palpitation (subjective, 心悸 ), cardiac output excessive sweating ( metabolism) weight loss ( protein) nervousness, irritability, tremour (CNS) exophthalmos ( 眼球突出,eye signs)

65 Graves Eye Disease An abnormal protrusion of the eyeball in the orbit when observed from the side. Swelling within the orbital cavities and enlargement of the periorbital muscles behind the eyes Note the proptosis, lid retraction and stare

66 Hyperthyroidism Diagnoses Assessment of thyroid function increased serum T4 and T3 decreased serum TSH Treatments anti-thyroid drugs(inhibition of thyroid hormone synthesis by inhibiting thyroid peroxidase) partial thyroidectomy radioactive iodine (to radiate the gland with high energy gamma rays, 3 months max. effect)

67 Hypothyroidism Causes Primary (thyroid; autoimmune disease, partial thyroidectomy), secondary (pituitary gland) or tertiary (hypothalamus) Common cause an autoimmune disorder called Hashimoto s thyroiditis ( 桥本氏甲状腺炎 ). Antibodies against the thyroid are not stimulatory, but are part of an immune process that blocks and destroys thyroid function

68 Hypothyroidism Common Symptoms Decreased BMR Mental slowness Cold intolerance( metabolism) Dry cold skin( protein) Weight gain ( metabolism) Acroparesthesia ( 感觉异常,numbness/tingling of hands)

69 Hypothyroidism Common Symptoms Thick tongue Myxedema Goiter Slow speech Amenorrhea( 无月经 ) Constipation( 便秘, GI motility) Low sex drive Arteriosclerosis cardiac output (remember permissive effect of TH to epinephrine/norepinephrine).

70 Hypothyroidism Assessment of thyroid function low serum free T4 greatly elevated serum TSH Treatment thyroxine (T4) replacement

71 To be continued

Thyroid Gland 甲状腺. Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C541, Block C, Research Building, School of Medicine Tel:

Thyroid Gland 甲状腺. Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C541, Block C, Research Building, School of Medicine Tel: Thyroid Gland 甲状腺 Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C541, Block C, Research Building, School of Medicine Tel: 88208292 Outline Thyroid Hormones Types Biosynthesis Storage and Release