The Thyroid Gland

The Thyroid Gland

The Thyroid Gland

Figure 18.11a

Largest endocrine glands in the body,

Weighing ~ 20-25g.

Functions early in life for the development of brain cells (forming nerve terminals/ synapse/ dendrites/ myelin)

The Thyroid Gland---Structure

Figure 18.11b, c

Figure 18.12b

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 T3 and T4

Figure 18.12a

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

Iodide trap – active transport:

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

T3 = 1.8 ~2.9 nmol/L

T4 = 65 ~156 nmol/L

rT3 = 0.2 ~0.8 nmol/L

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 T4 due to its higher affinity

–Slow onset and long duration of action

Free form: 1% ( T3)

Transport of thyroid hormones

Metabolism of thyroid hormones

DeiodinationDeiodinase

T4 → T3 (45%), in coldnessT4→ rT3 (55%), in pregnancy, hungry, stress, kidney failure

Locations: liver, kidney, skeletal muscle

The Thyroid Gland - Regulation of Secretion

Effects of T3 and T4 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 T3 and T4 on the Body: Calorigenic effect

Carbohydrate metabolism

–↑glucose oxidation,↑effect of glucagon, cortisol and GH–↑glucogenesis and glycogenolysisToo 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 O2 & ↑metabolic end products from tissue →vasodilatation–↑cardiac output ensures sufficient O2 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 intakeIncrease secretion of digestive juicesIncrease mobility of GI tract – hyperthyroidism: diarrhea

Effects on muscleshyperthyroidism →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

– T3 and T4 act by binding to nuclear receptors– T3 has 10 times the affinity for thyroid receptor as T4– ↑ Transcription of large numbers of genes– ↑ Synthesis of great numbers of proteins

The HPT axis

Wolff - Chaikoff Effect(autoregulation by Iodine)– low Iodine intake stimulates ‘iodide trap’– high Iodine intake (>2 mg/day) inhibits ‘iodine trap’ and TH synthesis

T4 is converted into T3 in pituitary and T3 acts as the final effector to turn off TSH

– TRH

Tripeptide;↑ TSH secretion; Cold TRH release ↑

PLC-DAG-PKC途径调节靶基因转录，促进 TSH合成

IP3-Ca2+途径促进 TSH爆发性释放

– TSH

• Glycoprotein

• ↑ T3, T4 synthesis and release

• ↑ thyroid cell size

• cAMP mediated mechanism

The Thyroid Gland- Diseases: Goiter