Korean, Edit

Chapter 20. Endocrine System

Recommended Article: 【Biology】 Biology Table of Contents

1. Endocrine System

2. Types of Hormones

1. Endocrine System

⑴ Endocrine: Transmission of signals without ducts

⑵ Types of endocrine signaling

① Autocrine: When a cell secretes an endocrine substance that acts on itself.

○ Examples: Tumor cells and growth factors, IL-2 from activated helper T cells, Growth factors from gastric cells.

② Paracrine: Signaling to neighboring cells

○ Example: Growth factors, interleukins, prostaglandins, histamine

○ Insulin-like growth factor (IGF): Secreted by the liver

○ Prostaglandin: promotes gastric mucin secretion, platelet release reaction, immune activity, and uterine contraction. Due to its unstable molecular structure, it functions as a local regulator.

○ Histamine: stimulates gastric acid secretion; induces bronchial smooth muscle contraction and mucus secretion; promotes mental alertness; causes vasodilation during inflammatory responses; induces uterine contraction; and relaxes smooth muscle.

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

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, antagonism

○ Sweating is controlled only by sympathetic nerves; no antagonism 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 hormones

○ Pathway: Cell membrane receptors → Signal transduction cascade → Enzyme activation ⇢ Gene expression and protein synthesis

○ Pre-synthesized and stored

○ Amine hormones (excluding thyroxine) and 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: a peptide hormone synthesized in the ribosome but not yet processed.

○ Prohormone: a peptide hormone in which the N-signal has been cleaved in the rough endoplasmic reticulum.

○ 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, thyroxine, 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 in the smooth endoplasmic reticulum as needed.

○ 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

**2. Types of Hormones **

⑴ Hypothalamus: The control center for homeostasis (body temperature, appetite, thirst, and reproduction)

① Anterior pituitary

○ Neurosecretory cells of the hypothalamus secrete releasing/inhibiting hormones into the median eminence (autocrine) → regulate the secretion of glandular hormones from the anterior pituitary.

○ Portal system

○ A capillary junction of different origins (e.g., anterior pituitary)

○ Does not mix with the general circulation blood.

○ Type 1. CRH (Adrenocorticotropic Hormone Releasing Hormone) ―⊕→ ACTH (Adrenocorticotropic Hormone)

○ Type 2. TRH (Thyroid Stimulating Hormone Releasing Hormone) ―⊕→ TSH (Thyroid Stimulating Hormone)

○ TSH: Promotes thyroid development, regulates expression of thyroid hormones, calcitonin, PTH, etc.

○ TSH receptors are located on cell membranes

○ Type 3. GnRH (Gonadotropin Stimulating Hormone 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: Neurosecretory cells, whose nuclei (cell bodies) are located in the hypothalamus, secrete neurohormones into the posterior pituitary.

○ Type 1. Neuroendocrine signaling

○ Type 2. Oxytocin

○ Stimulates uterine smooth muscle contraction to promote parturition

○ Secretion of milk from breasts during lactation

○ Also involved in love 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

⑵ Autonomic Nervous System and Endocrine System

① Autonomic nerves: Peripheral nerves independent of cerebral control

② Medulla Oblongata: Center of the autonomic nervous system

③ Acetylcholine (Ach) receptors

○ Muscarinic cholinergic receptor

○ Found at the terminal synapses of all parasympathetic postganglionic nerve fibers

○ Also found in the brain, heart, and smooth muscles

○ Present in the sinoatrial (SA) node, G-protein coupled receptor (GPCR) but not in cardiac muscle fibers of the heart

○ Responsive to muscarine

○ Nicotinic Cholinergic Receptor

○ Found in autonomic ganglia, neuromuscular junctions, and the central nervous system

○ Not present in the sinoatrial (SA) node or cardiac muscle fibers

○ Excitatory receptors that enable rapid neurotransmission

○ When acetylcholine binds, both Na⁺ and K⁺ can pass through, but Na⁺ permeability is greater, leading to depolarization

○ Named “nicotinic receptors” because they respond 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 (SA) node to increase heart rate, and acts on cardiac muscle cells to increase stroke volume

○ The ciliary muscle contracts, causing the lens to become thinner.

○ 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, and doesn’t act on cardiac muscle cells

○ The ciliary muscle relaxes, causing the lens to become thicker.

○ Nicotinic receptors act on both sympathetic and parasympathetic nervous systems, with one system dominant depending on the tissue

Figure 4. Types and composition of efferent neurons in the peripheral nervous system

⑶ Thyroid Gland

① Type 1. T₃, T₄: Lipophilic hormones

○ T₄ (thyroxine): Precursor; contains four iodine atoms; primarily secreted in 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)

○ The thyroid gland senses the blood calcium ion concentration on its own and secretes calcitonin.

○ Functions **: Reduces blood Ca²⁺, PO₄^2-

○ Stimulates osteoblasts

○ Reduces Ca²⁺ reabsorption in the distal tubules of the renal nephron.

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 (toxic diffuse goiter): Low TSH levels, high thyroxine levels

○ An autoimmune disease that produces anti-TSH receptor antibodies acting as receptor agonists.

○ Thyroid hormones continue to be secreted from the thyroid gland even when their levels increase.

○ The type of anti-TSH receptor antibody is IgG.

○ Newborns of mothers with Graves’ disease receive anti-TSH receptor antibodies from the mother, causing impaired TSH receptor function.

○ This leads to high plasma TSH levels in newborns due to compensatory response

○ Symptoms: Increased heart palpitations, protrusion of the eyeballs, rapid speech, and severe tremors when extending the hands and arms.

○ Also known as Basedow’s disease

○ Example 2. Goiter (Thyroid Enlargement): Reduced iodine intake → ↑ hypothalamic stimulation → Enlarged thyroid gland

○ Iodine is abundant in sea salt and seaweed but deficient in rock salt.

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 PO₄^2-

○ Reason for decreased phosphate: Although it increases locally, its reabsorption in the kidneys does not occur and its excretion is promoted.

○ Stimulates osteoclasts

○ Promotes Ca²⁺ reabsorption and inhibits phosphate reabsorption in the distal tubules of the renal nephron.

○ Activates Vitamin D

○ Functions: Increases blood Ca²⁺ and PO₄^2- (compensatory effect).

○ 1^st. Skin: 7-dehydroxycholesterol becomes cholecalciferol (vitamin D₃) by UV light

○ 2^nd. Liver: Cholecalciferol becomes 25-OH vitamin D₃ through 25-hydroxylase

○ 3^rd. Kidney: 25-OH vitamin D₃ becomes calcitriol (1,25-(OH)2 vitamin D₃) through 1α-hydroxylase

○ 4^th. Small intestine: Calcitriol, as active vitamin D, promotes calcium absorption

○ Active vitamin D promotes the creation of calcium-binding proteins, increasing calcium absorption in intestine and calcium concentration in the blood.

○ During calcium absorption, phosphate is co-transported, so when calcium concentration increases, phosphate concentration also increases.

② Hyperparathyroidism

○ Example: Calcium phosphate stones

③ Hypoparathyroidism

○ Example: Tetany disease, excessive Na+ channel activation

Figure 5. Thyroid (㉠) and Parathyroid (㉡) Glands

⑸ Islets (Pancreas): Regulated by the Autonomic Nervous System

① Type 1. Glucagon: Increases blood glucose concentration

○ Secreted by pancreatic islet α cells.

○ Released via autocrine secretion or regulated by sympathetic nervous system.

○ Gluconeogenesis: Glycogen → Glucose (Liver, muscle)

○ Inhibits glycolysis.

② Type 2. Insulin: Decreases blood glucose concentration

○ Secreted by pancreatic islet β cells.

○ Released via autocrine secretion or regulated by sympathetic nervous system.

○ Structure: Composed of 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

○ 1^st. Glucose enters β cells via GLUT2 on the cell membrane

○ 2^nd. Glucose produces ATP within β cells

○ 3^rd. Increased ATP concentration leads to closure of ATP-gated K+ channels on the cell membrane

○ 4^th. Depolarization of the cell membrane opens voltage-gated Ca2+ channels

○ 5^th. Increased intracellular Ca2+ leads to fusion of insulin granules with the cell membrane

○ 6^th. 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

○ Number 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 δ cells

○ Two active forms in nature: 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 Disease: 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

④ Diabetes Mellitus

○ Definition: Postprandial blood glucose ≥ 200 mg/dL or fasting blood glucose ≥ 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) used for gluconeogenesis → acetyl-CoA used for ketoacid synthesis → ketoacidosis → frequent 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 medulla – Zona reticularis – Zona fasciculata – Zona glomerulosa – Adrenal cortex

○ Zona reticularis: Sex hormones

○ Zona fasciculata: Cortisol

○ Zona glomerulosa: Aldosterone

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; conversion of glycogen, protein (amino acid deamination), and fat to glucose.

○ Function 2: Immune system suppression (e.g., inhibition of inflammatory response)

○ Dexamethasone, similar to corticol, 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

○ A methyl group is added to cortisol, hydrogen is replaced by fluorine, and a double bond is introduced.

○ 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, striae

○ 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 recovered

○ High dose (8 mg) dexamethasone: Decreased ACTH, decreased cortisol. Negative feedback 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 negative feedback recovery

○ Low dose (2 mg) dexamethasone: No change in ACTH, decreased cortisol. Not recovered.

○ High dose (8 mg) dexamethasone: No change in ACTH, no change or decrease in cortisol. Even strong negative feedback does not lead to recovery.

○ Ectopic ACTH Syndrome

○ Low dose (2 mg) dexamethasone: No change in ACTH, no change or increase in cortisol. Not recovered.

○ High dose (8 mg) dexamethasone: No change in ACTH, no change or increase in cortisol.

○ Normal

○ Low dose (2 mg) dexamethasone: Decreased ACTH, decreased cortisol. Normalized

○ High dose (8 mg) 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

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

○ The adrenal medulla is a modified postganglionic neuron of 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

○ Visceral small artery: Epinephrine α receptor → small artery constriction → decreased blood flow to visceral muscle → visceral muscle relaxation

○ 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 the development of 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

⑺ Sex Hormones

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

○ 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