The Thyroid Gland
The Thyroid Gland
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)
Figure 18.11a
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
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
T3 = 1.8 ~2.9
nmol/L
T4 = 65 ~156
nmol/L
rT3 = 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 T4 due to its higher affinity
–Slow onset and long duration of action
Free form: 1% ( T3)
Metabolism of thyroid hormones
Deiodination
Deiodinase
T4 → T3 (45%), in coldness
T4→ 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 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 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 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
– 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
T4 is converted into T3 in
pituitary and T3 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
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