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

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

2 Outline Thyroid Hormones Types Biosynthesis Storage and Release Transport Physiological Functions Mechanisms of TH action Regulation of thyroid hormone secretion Thyroid disorders

The Thyroid Gland Located at anterior part of neck on either side

Rich in blood supply Thyroid gland becomes functional early in

3 The Thyroid Gland Located at anterior part of neck on either side of trachea The thyroid gland straddles the trachea, just below the larynx, in the neck. One of the largest endocrine glands Comprised of 2 lobes; 20 g wt Rich in blood supply 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)

4 The Thyroid Gland Thyroid follicular cell T 4 and T 3 increase metabolic rate 4 3 Parafollicular cell (C cell) Calcitonin regulates calcium metabolism

5 Thyroid Gland Follicle The thyroid gland is composed of many follicles Each follicle contains colloid (thyroglobulin, TG +hormones) Colloid is absorbed back into the follicle epithelial cells upon stimulation Follicular cells take part in almost all stages of TH synthesis and secretion

6 Types of Thyroid Hormones 90% of metabolically active hormones secreted by thyroid is thyroxine (T 4 ), 10% is triiodothyronine (T 3 ), and less than 1% is rt3 Iodide is required (1mg/week) for thyroid hormone synthesis

7 Thyroid Hormones Thyroxine (T 4 ) Major hormone released from thyroid follicles Contains 4 iodine atoms More abundant than T 3

8 Thyroid Hormones Triiodothyronine (T 3 ) Generally formed from T 4 by cleaving an iodine molecule (deiodinase in target cells) 4timesmore more potent than T 4 Contains 3 iodine atoms

9 Biosynthesis of Thyroid Hormones

10 Biosynthesis of Thyroid Hormones Materials Iodine (in the form of iodide-i - ) Iodide is a necessary factor for TH synthesis Iodide (1mg/week) is required for TH synthesis From circulation Iodized table salt (1 sodium iodide/100,000 NaCl)

11 Biosynthesis of Thyroid Hormones Materials Tyrosine Thyroglobulin (TG): a large glycoprotein Synthesized by thyroid follicular cells Secreted across the apical membrane The principal component of colloid A precursor of TH A storage form of TH

12 Biosynthesis of Thyroid Hormones Iodine/iodide trapping Sodium/iodide symporter Maintains thyroid/plasma ratio of 30:1 Oxidation of iodide TPO(at the apical border) 2I - + H 2 O 2 I 0 (iodine free radical) Iodination of tyrosine TPO (an apical membrane enzyme) MIT and DIT Formation of T3, T4 by coupling TPO MIT + DIT T 3 DIT + DIT T 4 MIT-monoiodotyrosine DIT-diiodotyrosine TPO-thyroid peroxidase

14 Storage and Release of Thyroid Hormones Storage In the follicles In the form of TG (30 T4) For 2 ~3 months Release Stimulated t by TSH Concentration in plasma T 3 : 1.2 ~3.4 nmol/l T 4 : 85 ~142 nmol/l

15 Transport of T 4 and T 3 to the Tissues Binding form:99% Most T 4 and T 3 bound to plasma proteins synthesized by liver: Thyroxine-binding globulin (TBG): mainly Thyroxine-binding prealbulmin (TBPA) albulmin l Slowly released to the tissue cells, slower for T 4 due to its higher affinity Slow onset and long duration of action Free form:1% ( T 3 )

16 Physiological Functions of TH TH exerts widespread and diverse effects throughout the body. Effect on Growth Metabolism Nervous System Cardiovascular System GI Muscles, sexual function

growth and development of brain (fetus and neonate) Have

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

18 Effects of TH on Growth Cretinism: -deficiency of thyroid hormone during the period of fetal and early neonatal development -short, stocky stature & mental retardation -reversed with iodine and TH administration shortly after birth

19 Metabolic Effects of TH Increase cellular metabolic activity Calorigenic action BMR number & activity of mitochondria ATP Na +, K + -ATPase heat production O 2 consumption & BMR; CO 2 production ventilation

20 Metabolic Effects of TH Carbohydrate metabolism glucose oxidation, effect of E, glucogon, cortisol and GH gluconeogenesis and glycogenolysis Too much blood glucose (Diabetes) Fat metabolism lipolysis (Triglyceride FFA + glycerol) Oxidation of free fatty acid serum cholesterol(excretion hl l( into GI) ) Protein metabolism Protein synthesis (normal) Protein catabolism (hyperthyroidism) -hyperthyroidism: weight loss - hypothyroidism:myxedema (glycosaminoglycans trapped with water accumulate in the interstitial space)

21 Effects of TH on Nervous System Important t for maturation ti of CNS in perinatal period Enhance wakefulness, alertness, responsiveness to various stimuli, auditory sense, awareness of hunger, memory and learning capacity 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

22 A baby suffering from congenital hypothyroidism

23 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 th slightly increase of thyroid hormone increases heart strength marked increase of thyroid hormone decreases heart strength stroke volume + peripheral resistance pulse pressure

24 Effects of TH on GI Increase appetite and food intake Increase secretion of digestive juices Increase mobility of GI Diarrhea often results from hyperthyroidism

25 Effects of TH On muscles hyperthyroidism muscle weakening (catabolic effect) fine muscle tremor is a characteristic sign for hyperthyroidism hypothyroidism muscles sluggish On other endocrine glands secretion of insulin and cortisol On sexual function loss of libido impotency abnormal menstruation

times the affinity for thyroid receptor as T 4 Transcription

26 Mechanisms of TH action T 3 and T 4 act by binding to nuclear receptors which are expressed in most tissues T 3 has 10 times the affinity for thyroid receptor as T 4 Transcription of large numbers of genes Synthesis y of great numbers of proteins

27 Overall Effects of Thyroid Hormones Mnemonic T 3 functions-4b s Brain maturation Bone growth Beta-adrenergic effects BMR increases

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

29 Hypothalmico-pituitary-thyroid pituitary thyroid axis Hypothalamus TRH Tripeptide TSH secretion Cold: TRH release

Size of the thyroid cells Hyperthyroidism thyroid

30 Hypothalmico-pituitary-thyroid pituitary thyroid axis Pituitary TSH Glycoprotein T 3, T 4 synthesis and release Size of the thyroid cells Hyperthyroidism thyroid stimulating immunoglobulin (TSI) Anti-TSH receptor antibody Stimulate TSH receptor

31 Hypothalmico-pituitary-thyroid pituitary thyroid axis Thyroid Feedback effect of thyroid hormone T 4 is converted into T 3 in pituitary and T 3 acts as the final effector to turn off TSH

32 Iodine-Deficiency

33 Iodine-Deficient Goiter TSH is a trophic hormone, it stimulates not only T 3 /T 4 secretion but also protein synthesis in follicular cells. Therefore, size

34 Changes in feedback relationships in several disorders

35 Wolff-Charkoff effect autoregulation by I low I intake stimulates synthesis and iodide trap high I intake (>2 mg/day) inhibits trap function and synthesis. (a protective downregulation of TH production)

36 Disorders of the thyroid Hyperthyroidism Hypothyroidism Symptoms Hyperactivity, irritability Mental sluggishness Heat intolerance, sweating Cold intolerance Palpitations Fatigue, weakness Diarrhea Hair loss, oily skin Oligomenorrhea, loss of libido Weight loss, robust appetite polyuria Dyspnea Fatigue, weakness Constipation Hair loss, dry skin Menorrhagia, loss of libido Weight gain, poor appetite paresthesias

37 Disorders of the thyroid Hyperthyroidism Signs Tachycardia Bradycardia Tremor Goiter Warm, moist skin Proximal muscle weakness Exophthalmos Lid retraction, lid lag Hypothyroidism Delayed deep tendon reflex relaxation phase Goiter Dry, doughy skin Carpal tunnel syndrome Periorbital edema Puffy face, hands, and feet (myxedema) Peripheral edema

38 QUIZ An absence of thyroid hormones during fetal development leads to a. Acromegaly. b. Cushing's Syndrome. c. Cretinism. d. Grave's disease. e. Addison'ss disease.

39 QUIZ An absence of thyroid hormones during fetal development leads to a. Acromegaly. b. Cushing's Syndrome. c. Cretinism. d. Grave's disease. e. Addison's disease.

40 QUIZ A subject consuming a diet deficient i in iodine is likelyl to have a. a low plasma concentration of thyroxine due to reduced secretion of TSH by the pituitary gland. b. a low plasma concentration of thyroxine and an enlarged thyroid gland. c. a high plasma concentration of TSH. d. a low plasma concentration of thyroxine due to reduced secretion of TSH by the pituitary gland and a low plasma concentration of thyroxine and an enlarged thyroid gland. e. a low plasma concentration of thyroxine and an enlarged thyroid gland and a high plasma concentration of TSH.

41 QUIZ A subject consuming a diet deficient i in iodine is likelyl to have a. a low plasma concentration of thyroxine due to reduced secretion of TSH by the pituitary gland. b. a low plasma concentration of thyroxine and an enlarged thyroid gland. c. a high plasma concentration of TSH. d. a low plasma concentration of thyroxine due to reduced secretion of TSH by the pituitary gland and a low plasma concentration of thyroxine and an enlarged thyroid gland. e. a low plasma concentration of thyroxine and an enlarged thyroid gland and a high plasma concentration of TSH.

42 Summary Types of Thyroid Hormones thyroxine (T4) triiodothyronine (T3) Biosynthesis of Thyroid Hormones Iodine/iodide trapping Oxidation of iodide Iodination of tyrosine Formation of T3, T4 by coupling Storage and Release of Thyroid Hormones Transport of T4 and T3

43 Summary Physiological Functions of TH Effect on Growth, Metabolism, Nervous System, Cardiovascular System, GI Mechanisms of TH action Regulation of thyroid hormone secretion Hypothalmico-pituitary-thyroid axis Wolff-Chaikoff Effect Thyroid disorders Hyperthyroidism y Hypothyroidism

44 Then End.

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