Chapter 20. Endocrine System
Recommended Article : 【Biology】 Biology Table of Contents
1. Endocrine System
⑴ Endocrine : Transmission of signals without ducts
⑵ Types of endocrine signaling
① Autocrine : Cell-secreted molecules influencing themselves
○ Example : Tumor cells and growth factors, activated T cells’ IL-2, gastric cells’ growth factors
② Paracrine : Signaling to neighboring cells
○ Example : Growth factors, interleukins, prostaglandins, histamine
○ Insulin-like growth factor (IGF) : Secreted by the liver
○ Prostaglandin : Stimulation of mucus secretion, immune activation, uterine contractions; locally regulated due to unstable molecular structure
○ Histamine : Stomach acid secretion, bronchial smooth muscle contraction, mucus secretion, mental alertness, vasodilation during inflammation, uterine contractions, smooth muscle relaxation
③ Neurotransmitter : Electric signals, released at synapses
○ Example : Acetylcholine
④ Endocrine : Secreted into the bloodstream
○ Example : Hormones
⑤ Exocrine : Secreted into external body cavities
○ Example : Digestive enzymes, pheromones
Figure 1. Types of endocrine signaling [Footnote:1]
⑶ Characteristics of hormones
① Chemical substances regulating body responses even in small amounts : 10^-8 ~ 10^-12 M
② Transported through the blood
③ Specific actions : Target cells of hormone responses possess receptors
○ Sex hormones act on nearly all cells
④ Homeostasis maintenance : Feedback regulation, negative feedback
○ Sweating is controlled only by sympathetic nerves, no negative feedback occurs
○ Hormone half-lives are generally shorter than 3 minutes to maintain homeostasis
⑤ Lack of species specificity : Hormones are crucial for homeostasis, thus evolutionarily conserved
⑷ Classification of hormones
① Receptor-mediated hormones
○ Pathway : Cell membrane receptors → Signal transduction cascade → Enzyme activation ⇢ Gene expression and protein synthesis
○ Pre-synthesized and stored
○ Except for thyroxine, amine hormones, peptide hormones
○ Act much faster than lipid-soluble hormones
② Lipid-soluble hormones
○ Pathway : Bound to plasma carrier proteins, transported to tissues → Receptor inside the cytoplasm → Gene expression
○ Synthesized and secreted as needed
○ Steroid hormones, thyroid hormones, nitric oxide (NO), adrenal cortex hormones
③ Peptide hormones
○ Pre-synthesized and stored
○ Preprohormone: Synthesized in ribosomes but not yet processed peptide hormone
○ Prohormone: Peptide hormone with N-signal cleaved in the Golgi apparatus
○ When prohormone is processed in the Golgi apparatus, it becomes the final active form
○ Example : FSH, LH, insulin, etc.
④ Amine hormones
○ Insulin, histamine, catecholamines, calcitonin, melatonin, serotonin
○ Catecholamines: A group of hormones derived from tyrosine (e.g., dopamine, tyrosine, epinephrine, norepinephrine); pre-synthesized and stored
○ Thyroxine: Lipid-soluble, pre-synthesized and stored, bound to plasma carrier proteins and delivered to target tissues
⑤ Steroid hormones
○ Derived from cholesterol
○ Synthesized on demand by secretory vesicles
○ Bound to plasma carrier proteins and delivered to target tissues
○ Named with endings like -rone, -sol, -gen
Figure 2. Pathways of receptor-mediated and lipid-soluble hormones [Footnote:2]
**2. Types of Hormones **
⑴ Hypothalamus : Central regulation (body temperature, appetite, thirst, and reproduction)
① Hypothalamic-pituitary axis
○ Hypothalamic neurosecretory cells release/inhibit hormone secretion at median eminence → Regulation of hormone secretion in the anterior pituitary
○ Portal system
○ Different origin capillary junctions (e.g., median eminence)
○ Does not mix with general circulation
○ Type 1. CRH (Corticotropin-Releasing Hormone) ―⊕→ ACTH (Adrenocorticotropic Hormone)
○ Type 2. TRH (Thyrotropin-Releasing Hormone) ―⊕ → TSH (Thyroid-Stimulating Hormone)
○ TSH : Promotes thyroid development, regulates expression of thyroid hormones, calcitonin, PTH
○ TSH receptors are located on cell membranes
○ Type 3. GnRH (Gonadotropin-Releasing Hormone) ―⊕ → FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone)
○ Type 4. GHRH (Growth Hormone-Releasing Hormone) ―⊕ → GH (Growth Hormone) → Bone growth, protein synthesis, cell division
○ Comparison of GH and insulin
○ GH : Increases blood glucose and fatty acids
○ Insulin : Decreases blood glucose and fatty acids
○ Other functions of GH and insulin are similar
○ Insulin-like Growth Factor (IGF)
○ Can stimulate IGF secretion in the liver
○ IGF exhibits response in bones and cartilage
○ Vascular Endothelial Growth Factor (VEGF)
○ Protein secreted by oxygen-deprived cells like cancer cells
○ Promotes angiogenesis, vascular binding, etc.
○ Type 5. GHRIH (Growth Hormone-Releasing Inhibiting Hormone) ―⊝ → GH
○ Type 6. PRH (Prolactin-Releasing Hormone) ―⊕ → PRL (Prolactin) → Milk production in breasts
○ Promotes mammary development and lactation in females
○ Secreted in non-lactating females and males
○ Additional functions: Immunomodulation, angiogenesis
○ Type 7. PRIH (Prolactin-Releasing Inhibiting Hormone) ―⊝ → PRL
○ Type 8. MSHRH (Melanocyte-Stimulating Hormone-Releasing Hormone) ―⊕ → MSH (Melanocyte-Stimulating Hormone)
○ MSH is also called intermedin or melanotropin
○ MSH is secreted from the intermediate lobe of the pituitary gland
○ α-MSH is a polypeptide with 13 amino acids and a molecular weight of 1823 (3%)
○ β-MSH is a polypeptide with 22 amino acids and a molecular weight of 2734 (97%)
○ Type 9. MSHRIH (Melanocyte-Stimulating Hormone-Releasing Inhibiting Hormone) ―⊝ → MSH
② Posterior pituitary : Hormone-secreting nerve cells in the posterior pituitary controlled by nuclei (cell bodies) of hypothalamic neurosecretory cells
○ Type 1. Neuroendocrine signaling
○ Type 2. Oxytocin
○ Induces contraction of uterine smooth muscle, promoting labor
○ Secretion of milk from breasts during lactation
○ Also involved in bonding and maternal behavior
○ Type 3. Antidiuretic Hormone (ADH)
○ Also called vasopressin
○ Involved in reabsorption of water in kidneys
○ Drinking alcohol inhibits ADH secretion, leading to increased urination
Figure 3. Hypothalamic Hormones [Footnote:3]
⑵ Autonomic Nervous System and Endocrine System
① Autonomic nervous system : Peripheral nerves not under the control of the brain
② Medulla : Central region of the autonomic nervous system
③ Acetylcholine (Ach) receptors
○ Found at terminal synapses of all postganglionic sympathetic fibers
○ Also found in the brain, heart, and smooth muscles
○ G-protein coupled receptor (GPCR), not present in the sinoatrial node but in cardiac muscle fibers
○ Responsive to muscarine
○ Found in autonomic ganglia, neuromuscular junctions, and central nervous system
○ Not present in the sinoatrial node or cardiac muscle fibers
○ Enables fast nerve transmission as an excitatory receptor
○ When acetylcholine binds, both Na+ and K+ ions can pass through, but Na+ permeability is higher, leading to depolarization
○ Named as a nicotinic receptor due to its response to nicotine
④ Structure of the Sympathetic Nervous System
○ Length of preganglionic nerve ↓, length of postganglionic nerve ↑
○ Ach secretion in preganglionic nerve : Nicotinic receptor
○ Epinephrine and norepinephrine secretion in postganglionic nerve
○ Ach secretion in sweat glands from postganglionic nerve
⑤ Structure of the Parasympathetic Nervous System
○ Length of preganglionic nerve ↑, length of postganglionic nerve ↓
○ Ach secretion in preganglionic nerve : Nicotinic receptor
○ Ach secretion in postganglionic nerve : Muscarinic receptor
⑥ Functions of the Autonomic Nervous System
○ Antagonistic actions of the sympathetic and parasympathetic nervous systems
Table. 1. Antagonistic Actions of the Sympathetic and Parasympathetic Nervous Systems
○ Sympathetic nervous system : Associated with the fight-or-flight response
○ Smooth muscles : Relaxation of visceral muscles, vasoconstriction
○ Acts on the sinoatrial node to increase heart rate, acts on cardiac muscle cells to increase stroke volume
○ Contraction of the arrector pili muscle leads to thinning of the hair
○ Skeletal muscles are controlled by somatic motor neurons, not affected by autonomic nervous system
○ Stimulates glucagon secretion and inhibits insulin secretion
○ Sympathetic nervous system inhibitor : Taurine
○ Parasympathetic nervous system : Associated with rest and relaxation
○ Smooth muscles : Contraction of visceral muscles, vasodilation
○ Acts on the sinoatrial node to decrease heart rate, doesn’t act on cardiac muscle cells
○ Contraction of the arrector pili muscle relaxes, causing thickening of the hair
○ Nicotinic receptors act on both sympathetic and parasympathetic nervous systems, with one system dominant depending on the tissue
Figure. 4. Types and Components of Peripheral Nervous System Neurons [Footnote:4]
⑶ Thyroid Gland
① Type 1. T3, T4 : Lipophilic hormones
○ T4 (Thyroxine) : Prohormone with 4 iodine atoms, primarily secreted by mammals
○ T3 (Triiodothyronine) : Active form with 3 iodine atoms, more reactive compared to T4, acts as T3 in almost all tissues
○ Functions : Increases metabolic rate, important for bone and neural development in mammals, involved in metamorphosis in amphibians
○ TSH ―⊕ → Secretion of T3, T4
② Type 2. Calcitonin (CT)
○ Parathyroid gland senses blood calcium ion concentration and secretes calcitonin
○ Functions **: Reduces blood Ca2+, PO42- **
○ Stimulates osteoblasts
○ Reduces Ca2+ reabsorption in the proximal convoluted tubule of nephrons
③ Hyperthyroidism
○ Excess secretion of T3, T4 leading to thyroid gland enlargement (similar to hypothyroidism)
○ Cause: ↑ TSH → Result: ↓ TRH, ↑ thyroxine
○ Cause: ↑ TRH → Result: ↑ TSH, ↑ thyroxine
○ Cause: ↑ thyroxine → Result: ↓ TRH, ↓ TSH
○ Example 1. Graves’ disease: Low TSH levels, high thyroxine levels
○ Autoimmune disorder generating autoantibodies that act as receptor agonists, stimulating TSH receptors
○ Despite increased thyroid hormone levels, hormone secretion continues due to TSH receptor stimulation
○ Autoantibodies of the type IgG
○ Infants born to mothers with Graves’ disease lack functional TSH receptors due to transplacental transfer of autoantibodies
○ This leads to high plasma TSH levels in infants due to compensatory response
○ Symptoms: Increased heart rate, bulging eyes, increased speech rate, severe tremors of hands and arms when extended
○ Also known as Basedow’s disease
○ Example 2. Goiter (Thyroid Enlargement): Reduced iodine intake → ↑ hypothalamic stimulation → Enlarged thyroid gland
○ Iodine is abundant in iodized salt or seaweed but deficient in endemic areas
④ Hypothyroidism
○ Very low secretion of T3, T4 leading to thyroid gland enlargement (similar to hyperthyroidism)
○ Example 1. Cretinism
○ Babies born to mothers with hypothyroidism during pregnancy show cretinism
○ Resulting in impaired intellectual development
⑷ Parathyroid Gland
① Type 1. Parathyroid hormone (PTH)
○ Parathyroid gland senses blood calcium ion concentration and secretes PTH
○ Functions : Increases blood Ca2+, decreases PO42-
○ Decreased phosphate levels due to local increase, lack of reabsorption in the kidney leading to increased excretion
○ Stimulates osteoclasts
○ Increases Ca2+ reabsorption and inhibits phosphate reabsorption in the proximal convoluted tubule of nephrons
○ Activates Vitamin D
○ Functions : Increases blood Ca2+, increases PO42- (compensatory effect)
○ 1st. Skin: 7-dehydroxycholesterol from UV light becomes cholecalciferol (vitamin D3)
○ 2nd. Liver: Cholecalciferol becomes 25-OH vitamin D3 through 25-hydroxylase
○ 3rd. Kidney: 25-OH vitamin D3 becomes calcitriol (1,25-(OH)2 vitamin D3) through 1α-hydroxylase
○ 4th. Small intestine: Calcitriol, as active vitamin D, promotes calcium absorption
○ Active vitamin D promotes the creation of calcium-binding proteins, increasing calcium absorption and concentration in the blood
○ Calcium absorption is associated with phosphate, so increased calcium concentration leads to increased phosphate concentration
② Hyperparathyroidism
○ Example: Hypercalciuria
③ Hypoparathyroidism
○ Example: Tetany, excessive Na+ channel activation
Figure. 5. Thyroid (A) and Parathyroid (B) Glands [Footnote:5]
⑸ Islets (Pancreas): Regulated by the Autonomic Nervous System
① Type 1. Glucagon: Increases blood glucose concentration
○ Secreted by pancreatic islet α cells (A cells)
○ Released via autocrine secretion or sympathetic nervous system regulation
○ Gluconeogenesis : Glucose → Glycogen (Liver, muscle)
○ Gluconeogenesis
② Type 2. Insulin: Decreases blood glucose concentration
○ Secreted by pancreatic islet β cells (B cells)
○ Released via autocrine secretion or sympathetic nervous system regulation
○ Structure : Comprises 51 amino acids forming a disulfide-bonded quaternary structure
○ Consists of a 21-amino acid chain and a 30-amino acid chain linked together
○ Mechanism
○ 1st. Glucose enters β cells via GLUT2 on the cell membrane
○ 2nd. Glucose produces ATP within β cells
○ 3rd. Increased ATP concentration leads to closure of ATP-gated K+ channels on the cell membrane
○ 4th. Depolarization of the cell membrane opens voltage-gated Ca2+ channels
○ 5th. Increased intracellular Ca2+ leads to fusion of insulin granules with the cell membrane
○ 6th. Insulin is released from β cells into the bloodstream
○ Function 1. Conversion of glucose to glycogen : Glucose → Glycogen (Liver, muscle)
○ Function 2. Conversion of glucose to protein, fat
○ Function 3. Increased glucose metabolism
○ Function 4. Degradation of residual amino acids in the blood (exception: tryptophan)
③ Type 3. Somatostatin (STT)
○ Secreted in the nervous system (hypothalamus), digestive system, endocrine system; in the digestive system, secreted by pancreatic islet δ cells (D cells)
○ Structure [Footnote:10]
○ 1 to 14 : Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys
○ Disulfide bond between Cys3 and Cys14
○ Phe7 to Thr10 forms a binding site
○ Function 1. Inhibits growth hormone (GH), TSH
○ Function 2. Inhibits exocrine, endocrine, paracrine, and autocrine functions
○ Reduces secretion of glucagon and insulin
○ Inhibits digestive actions, including reducing gastric secretion in response to increased blood glucose and amino acids, via D cells
○ Two active forms: SST14, SST28
○ Somatostatin receptors are GPCRs; five types exist: SSTR1 to SSTR5
○ SSTR2 is the most abundant receptor in tumors.
○ There are reports that SSTRs can form homodimers or heterodimers to initiate new signal transduction.
○ SRIF-14: Somatostatin Release Inhibitory Factor
○ Related Cancer Conditions: NET (Neuroendocrine Tumor)
○ GEP (Gastroenteropancreatic) NET accounts for about 80-100% of all NETs.
○ SST2 > SST1, SST5 > SST3 » SST4
○ SST2 is found in 70-90% of NETs.
○ Pharmaceutical Applications of Somatostatin
Table 2. Pharmaceutical Applications of Somatostatin [Footnote: 6]
④ Diabetes Mellitus
○ Definition: Postprandial over 200 mg/dL or fasting over 126 mg/dL
○ Common Symptoms
○ Oxygen deficiency due to increased blood viscosity, leading to necrosis, is the biggest issue: Eventually, amputation of the legs is necessary.
○ Increased urine secretion
○ Type I Diabetes Mellitus (Insulin-Dependent)
○ Autoimmune disorder where white blood cells destroy one’s own β-cells
○ Observed from teenage years
○ 80% of Type 1 diabetes patients have antibodies against the islet β-cells of Langerhans
○ Symptoms: Insulin deficiency, increased blood fatty acids, increased urine output
○ Symptoms: Increased gluconeogenesis → oxaloacetate (OAA) is directed towards glucose synthesis → acetyl coA is directed towards ketone synthesis → ketosis → constant fainting
○ Treatment: Resolved through insulin prescription
○ Type II Diabetes Mellitus (Insulin-Independent)
○ Definition: Genetic or acquired adult disease caused by insulin receptor gene abnormalities
○ Observed from the 40s
○ Cause: Habitual
○ Symptoms: Increased insulin secretion, increased blood fatty acids, increased urine output, obesity
⑹ Adrenal Gland
① Structure: Adrenal Capsule - Zona Glomerulosa - Zona Fasciculata - Zona Reticularis - Adrenal Medulla
○ Zona Glomerulosa: Mineralocorticoids
○ Zona Fasciculata: Cortisol
○ Zona Reticularis: Androgens
② Adrenal Cortex Hormones
○ Activated by ACTH and RAAS (Renin-Angiotensin-Aldosterone System)
○ ACTH stimulates cortisol and aldosterone secretion
○ RAAS stimulates aldosterone secretion
○ Type 1. Glucocorticoids (e.g., Cortisol): Long half-life
○ Function 1: Long-term stress response: Increased blood glucose, glycogen, protein breakdown (amino acid deamination), fat → glucose
○ Function 2: Immune system suppression (e.g., inhibition of inflammatory response)
○ Dexamethasone, similar to corticoids, is actually being used as an anti-inflammatory treatment
○ Function 3: Secretion varies with circadian rhythm (circadian clock)
○ Addison’s Disease: Cortisol deficiency
○ Dexamethasone:
○ Similar to cortisol but more effective
○ Methyl group in cortisol is replaced by a hydrogen in dexamethasone, and double bonds are added
○ Dexamethasone Suppression Test: Test to check for the presence (low dose) and location (high dose) of disease by injecting dexamethasone
○ Cushing’s Syndrome: More comprehensive term than Cushing’s Disease
○ Causes: Steroid intake, etc.
○ Symptoms: Increased cortisol, central obesity, buffalo hump, moon face
○ Cushing’s Syndrome = ACTH-dependent + ACTH-independent
○ ACTH-dependent = pituitary cushing syndrome + prostate gland cancer
○ ACTH-independent = adrenal Cushing’s syndrome + iatrogenic
○ Cushing’s Disease: Excessive cortisol secretion due to pituitary tumor
○ Low dose (2 mg) dexamethasone: No change in ACTH, no change in cortisol. Not normalized
○ High dose (8 mg) dexamethasone: Decreased ACTH, decreased cortisol. Suppression of adrenal through alternative pathway leads to recovery.
○ Primary Adrenal Cushing’s Syndrome: Excessive cortisol secretion due to adrenal tumor
○ Cortisol-secreting adrenal is not suppressed, so there is no recovery
○ Low dose (2 mg) dexamethasone: No change in ACTH, decreased cortisol. Not normalized
○ High dose (8 mg) dexamethasone: No change in ACTH, no change or decrease in cortisol. Strong negative feedback prevents recovery.
○ Ectopic ACTH Syndrome
○ Low dose (2 mg) dexamethasone: No change in ACTH, no change or increase in cortisol. Not normalized
○ High dose (8 mg) dexamethasone: No change in ACTH, no change or increase in cortisol.
○ Normal
○ Low dose dexamethasone: Decreased ACTH, decreased cortisol. Normalized
○ High dose dexamethasone: Decreased ACTH, decreased cortisol.
○ Type 2. Mineralocorticoids (e.g., Aldosterone)
○ Acts on the kidney’s Na+/K+ pump to promote reabsorption of water and Na+ → increase in blood pressure
○ Aldosterone is synthesized from cholesterol
○ ACTH ―⊕ → Corticoid Secretion
Figure 6. Steroid Hormone Biosynthesis Pathway in the Adrenal Cortex [Footnote: 8]
③ Adrenal Medulla Hormones
○ Overview
○ Type 1: Epinephrine (Adrenaline)
○ Type 2: Norepinephrine
○ Activated by the sympathetic nervous system
○ Adrenal medulla responds faster to stress compared to the adrenal cortex
○ Adrenal medulla neurons after ganglia change in the sympathetic nervous system
○ Function 1: Short-term stress response: Blood glucose ↑, blood pressure ↑ (vascular constriction), respiration ↑, heart rate ↑, metabolism rate ↑, digestive activity and kidney activity ↓
○ Dilates bronchioles in relation to increased respiration
○ Increased alertness
○ Short half-life
○ Function 2: Glycogen → Glucose (in liver, muscles): Not the primary response compared to Function 1
○ Epinephrine response varies depending on tissue type
○ Liver cells: Epinephrine β receptors → increased blood glucose levels
○ Skeletal muscle blood vessels: Epinephrine β receptors → vasodilation
○ Intestinal blood vessels: Epinephrine α receptors → vasoconstriction
○ Cardiac muscle and other smooth muscle arterioles: Epinephrine β receptors → arteriole dilation → increased blood flow → contraction of cardiac and other smooth muscles
○ Internal organ smooth muscle arterioles: Epinephrine α receptors → arteriole constriction → reduced blood flow to internal organs → relaxation of internal organ smooth muscles
○ Regulation: Increased sympathetic nervous system activity ―⊕→ Epinephrine and norepinephrine secretion
④ Small amounts of sex hormones (testosterone, estrogen) secreted from the adrenal cortex: Promotes and maintains sexual characteristics
⑤ Adrenal Glands and Aging
○ Adrenal glands are among the organs with the highest vitamin C content in the body
○ When stressed, adrenal hormones are secreted heavily, potentially depleting vitamin C in the body
○ Depletion of vitamin C leads to decreased antioxidant activity, promoting aging due to reactive oxygen species
⑻ Thymus Gland: Secretes thymosin and thymopoietin → Matures immature lymphocytes into T lymphocytes
⑼ Pineal Gland
① Light −⊕ → Photoreceptor ipRGC ―⊝ → Melatonin
② Melatonin ―⊕→ Suprachiasmatic Nucleus (SCN) ―⊕ → Sleep response
③ Melatonin
○ Circadian Rhythm Mechanism
○ Melatonin rhythm: Melatonin secretion increases at night and is used as a weak sleep aid
Figure 7. Melatonin Rhythm [Footnote: 9]
○ Melatonin secretion levels are higher in winter
⑽ Other Endocrine Organs
① Stomach: Regulates hydrochloric acid secretion through gastrin secretion
② Kidney: Secretes erythropoietin (EPO) → Stimulates red blood cell production in bone marrow
Input: 2015.07.26 22:11