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
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