The Thyroid Gland The Thyroid Gland Largest

The Thyroid Gland

The Thyroid Gland Largest endocrine glands in the body, Weighing ~ 20 -25 g. Functions early in life for the development of brain cells (forming nerve terminals/ synapse/ dendrites/ myelin) Figure 18. 11 a

The Thyroid Gland---Structure

Figure 18. 11 b, c

Figure 18. 12 b

The Thyroid Gland - Function 酪氨酸

Biosynthesis of Thyroid Hormones Iodine: - Distribution: the sea - Source: food (and drink), in the form of I-. The international recommended intake of iodine： 150 mg/day (1/3 is absorbed in the thyroid) The total iodine in the thyroid: 8 -10 mg (90% of the total iodine in body) Thyroglobulin (TG): - Homodimer glycoprotein - Carrier of iodotyrosine - The storage form of thyroid hormones

Biosynthesis of Thyroid Hormones

The Thyroid Gland - Production of T 3 and T 4

Figure 18. 12 a

Iodide trap – active transport: The sodium/iodide symporter ( 同向转运体，NIS) is an intrinsic membrane protein that mediates the active transport of iodide into the thyroid and other tissues thyroid peroxidase, TPO

The activation of the iodine is the precondition of tyrosine iodination:

Condensation of iodinated tyrosine:

The storage and release of thyroid hormones Storage –In the follicles –In the form of TG –For 2 ~3 months Release –Stimulated by TSH T 3 = 1. 8 ~2. 9 nmol/L T 4 = 65 ~156 nmol/L r. T 3 = 0. 2 ~0. 8 nmol/L

Transport of thyroid hormones Binding form: 99% Thyroid hormones attached to thyroid binding globulins (TBG) – Some are attached to transthyretin（甲状腺素运载蛋白）, Thyroxine -binding prealbulmin (TBPA，甲状腺素结合前白蛋白) or albumin –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)

Metabolism of thyroid hormones Deiodination Deiodinase T 4 → T 3 (45%), in coldness T 4→ r. T 3 (55%), in pregnancy, hungry, stress, kidney failure Locations: liver, kidney, skeletal muscle

The Thyroid Gland - Regulation of Secretion

Effects of T 3 and T 4 on the Body Proper development of the nervous system in the fetus; Maintain a person's alertness, responsiveness, and emotional state.

Essential for growth in children - Promote bone formation and maturation, and the development of brain (fetus and baby) Synergistic effect（协同效应）with GH, IGF-1, insulin and other growth factors Cretinism: deficiency of thyroid hormone during the period of fetal and early neonatal development; short, stocky stature & mental retardation

Permissive Effects on catecholamines – Up-regulate beta-adrenergic receptors in many tissues (heart and nervous system) – Potentiate (↑the effect of, being synergistic) actions of catecholamines (i. e. hyperthyroidism resembles symptoms of hypersecretion of epinephrine/norepinephrine)

Effects of T 3 and T 4 on the Body: Calorigenic effect

Carbohydrate metabolism –↑glucose oxidation, ↑effect of glucagon, cortisol and GH –↑glucogenesis and glycogenolysis Too much TH →↑blood glucose (Diabetes) Fat metabolism –↑lipolysis (Triglyceride → FFA + glycerol) –↑oxidation of FFA –↓serum cholesterol (excretion into GI) Protein metabolism –↑Protein synthesis (normal) –↑Protein catabolism (hyperthyroidism)

Effects on Nervous System A key role on the CNS-maturation during perinatal period ↑ wakefulness, alertness, responsiveness to various stimuli, auditory sense, awareness of hunger, memory and learning capacity Normal emotional tone also depends on proper thyroid hormone ↑ the speed and amplitude of peripheral nerve reflexes Hyperthyroidism: hyperexcitability, insomnia, loss of concentration Hypothyroidism: mental retardation, sleepiness myxedema

Effects on cardiovascular system ↑ 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 ↑ heart rate –↑adrenergic activity (↑response to adrenaline/noradrenaline） –↑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 ↑

Effects on gastrointestinal system Increase appetite and food intake Increase secretion of digestive juices Increase mobility of GI tract – hyperthyroidism: diarrhea Effects on muscles hyperthyroidism →muscle weakening (catabolic effect), fine muscle tremor (characteristic sign) hypothyroidism →muscles sluggish Effects on other endocrine glands ↑secretion of insulin and cortisol Effects on sexual function – loss of libido – impotency – abnormal menstruation

Working mechanism of thyroid hormones – T 3 and T 4 act by binding to nuclear receptors – T 3 has 10 times the affinity for thyroid receptor as T 4 – ↑ Transcription of large numbers of genes – ↑ Synthesis of great numbers of proteins

The HPT axis T 4 is converted into T 3 in pituitary and T 3 acts as the final effector to turn off TSH Wolff - Chaikoff Effect (autoregulation by Iodine) – low Iodine intake stimulates ‘iodide trap’ – high Iodine intake (>2 mg/day) inhibits ‘iodine trap’ and TH synthesis

– TRH Tripeptide; ↑ TSH secretion; Cold TRH release ↑ PLC-DAG-PKC途径调节靶基因 转录，促进TSH合成 IP 3 -Ca 2+途径促进TSH爆发性 释放

– TSH • Glycoprotein • ↑ T 3, T 4 synthesis and release • ↑ thyroid cell size • c. AMP mediated mechanism

The Thyroid Gland- Diseases: Goiter