Human body hormones and their functions | the endocrine system

Human Body Hormones and Their Functions | The Endocrine System

Human Body Hormones and Their Functions | The Endocrine System

Human Body Hormones and Their Functions | The Endocrine System

Overview

The Body’s Long-Distance Regulators 

  • Hormone definition: 
  • Hormones may reach all parts of the body But only certain types of cells (target cells) are equipped to respond 

Hormone (from the Greek Hormone (from the Greek horman, to excite), to excite) is a chemical signal secreted into the circulatory system and communicates regulatory messages within the body.

Two systems act individually and together in regulating an animal’s physiology

  • Endocrine system 
  • Constituted by hormone-secreting cells and glands 
  • Secretes hormones that coordinate slower but longer-acting responses to stimuli “ductless”

Two systems act individually and together in regulating an animal’s physiology

  • Nervous system 
  • Conveys high-speed electrical signals along specialized cells called neurons rapid messages control the movement of body parts. 

Endocrine cell & Neuron

Hormone composition

Three major classes of molecules function as hormones invertebrates 

  1. Proteins and peptides (soluble) 
  2. Amines derived from amino acids (soluble) 
  3. Steroids (insoluble)

Signaling by any of these molecules involves three key events 

  1. Reception 
  2. signal transduction 
  3. response 

Water-soluble hormones act on cell-surface receptors

Receptor 

  • Embedded in the plasma membrane

Signal transduction 

  • Converts an extracellular chemical signal to an intracellular response 

Response 

  • Cytoplasmic response Nuclear response eg: Glucagon (an 8-aa peptide) Camouflage mechanism

Intracellular Receptors for Lipid-Soluble Hormones

  • Steroids (estrogens, progesterone), thyroid hormones, and the hormonal form of vitamin D

Hormones: 

  • mostly nonpolar (lipid-soluble) diffusible

Receptor: 

  • located in the nucleus or trapped in the cytoplasm

Signal transduction 

  • usually perform the entire task of transducing signals within a target cell.

The same hormone may have different effects on target cells that have 

  • Different receptors for the hormone 
  • Different proteins for carrying out the response

Epinephrine 

  • Responds to short-term stress Resulting in decreased blood flow to the digestive tract and increased delivery of glucose to major skeletal muscles.

Paracrine Signaling by Local Regulators 

Various types of chemical signals elicit responses in nearby target cells Î More quickly than hormones can Examples: 

  • Neurotransmitters 
  • Cytokines/ growth factors: play a role in immune responses 
  • nitric oxide (NO): free radical, easy to breakdown (1998 Nobel) secreted by endothelial cells activates an enzyme that relaxes the neighboring smooth muscle cells Æ dilates the vessels and improves blood flow Viagra (sildenafil citrate)

Prostaglandins (PGs) (1982, Nobel Prize)

In the reproductive system 

  • First discovered in prostate–gland secretions -stimulate smooth muscles of the female’s uterus to contract 
  • Secreted by placenta cells during childbirth -induce labor

In the immune system

  • induce fever and inflammation; intensify the sensation of pain 

The anti-inflammatory drugs: aspirin and ibuprofen

In the circulation system

  • -regulate the aggregation of platelets In the circulation system 

 In the respiratory system

  •  Prostaglandin E signals the muscle cells to relax
  • Prostaglandin F signals the muscle cells to contract

The major human endocrine glands 

The pineal gland-Melatonin 

The primary functions of melatonin

  • Affects skin pigmentation in many vertebrates
  • Appear to be related to biological rhythms associated with reproduction
  • Release of melatonin
  • Is controlled by light/dark cycles
  • main target cells are in the part of the brain called the suprachiasmatic nucleus (SCN).

Relation Between the Hypothalamus and Pituitary Gland 

  • The hypothalamus, a region of the lower brain – Contains different sets of neurosecretory cells hypothalamus-pituitary

Relationship Between the Hypothalamus and Pituitary Gland 

  • The hypothalamus: a region of the lower brain
  • The pituitary gland: a lima bean-sized organ located at the base of the hypothalamus
  • The posterior pituitary ( neurohypophysis): -an extension of the hypothalamus -stores and secretes two hormones from the hypothalamus.

Posterior Pituitary Hormones

  • The two hormones released from the posterior pituitary 
  • Act directly on nonendocrine tissues 
  • Antidiuretic hormone (ADH) acts on the kidneys, increasing water retention and thus decreasing urine volume. 
  • Oxytocin acts on uterine muscles to contract during childbirth causes the mammary glands to eject milk during nursing.

The Anterior Pituitary 

  • A true-endocrine gland, controlled by the neurohormones from the hypothalamus
  • Synthesize and secrete at least eight different hormones directly into the blood.
  • Tropic hormones: Hormones that regulate the function of endocrine organs

Anterior Pituitary Hormones 

  • Produces both tropic and nontropical hormones

The four strictly tropic hormones are  

  • Follicle-stimulating hormone (FSH) 
  • Luteinizing hormone (LH) 
  • Thyroid-stimulating hormone (TSH) 
  • Adrenocorticotropic hormone (ACTH) 

Glycoprotein Hormone 

  • Gonadotropins: stimulate the activities of the male and female gonads 

ACTH

  • Peptide; stimulates the production and secretion of steroid hormones by the adrenal cortex.

Anterior Pituitary Hormones 

The nootropic hormones include 

  • Prolactin (PRL) Anterior Pituitary Hormones 
  • Stimulates mammary gland growth and lactation in mammals 
  • Regulates fat metabolism and reproduction in birds… 
  • Melanocyte-stimulating hormone (MSH)
  • Regulates the activity of pigment-containing cells in the skin of some fishes, amphibians, and reptiles. 
  • Act on neurons in the brain, inhibiting hunger in mammals
  • β-endorphin
  • Bind to brain receptors and inhibit the sensation of pain 
  • “Runner’s high” effects

Anterior Pituitary Hormones: Growth hormone (GH

  • Tropic action: signal the liver to release insulin-like growth factors (IGFs), which circulate stimulate bone/cartilage growth. 
  • Non-tropic action: exerts diverse metabolic effects that tend to raise blood glucose.
  • Nonpituitary hormones that regulate metabolism, homeostasis, etc. (tyrosine) http://www.answers.com/topic/thyroid-hormone
  • The thyroid gland consists of two lobes located on the ventral surface of the trachea Produces two iodine-containing hormones, triiodothyronine (T3) and thyroxine (T4).
  • T4 is converted to T3 by deiodinases.
  • Secretion of thyroid hormones is regulated by the hypothalamus and anterior pituitary hormones –two negative feedback loops TSH–releasing hormone TRH thyroid-stimulating hormone.

The thyroid hormones play crucial roles in stimulating metabolism and influencing the development and maturation  

Other vertebrate studies:

  • The metamorphosis of a tadpole into a frog is required for the normal functioning of bone-forming cells and the branching of nerve cells during the embryonic development of the brain. 

In mammalian development, 

  • Thyroid hormones help maintain normal blood pressure, heart rate, muscle tone, digestion, and reproductive functions.
  • Important in bioenergetics, generally increasing the rate of oxygen consumption and cellular metabolism 

Hyperthyroidism

  • Lead to high body temperature, profuse sweating, weight loss, irritability, and high blood pressure. 

Graves’ disease

  • The tissue behind the eyes can become swollen and fibrous.
  • Hypothyroidism Can produce symptoms such as weight gain, lethargy, and intolerance to cold in adults. 

Goiter

  •  A deficiency of iodine in the diet TSH enlarges the thyroid.

Cretinism

  • Inherited condition of thyroid deficiency or lacked thyroid hormones in childhoods endemic cretinism in the Democratic Republic of Congo: Four inhabitants aged 15-20 years: a normal male and three females with severe longstanding hypothyroidism with dwarfism, retarded sexual development, puffy features, dry skin and hair, and severe mental retardation. From Delange (229). 

Calcitonin

  • Calcitonin peptide parathyroid glands four small structures embedded in the surface of the thyroid Parathyroid Hormone; PTH (from parathyroid glands) 

Blood calcium homeostasis.

  • Calcitonin and Parathyroid Hormone Osteoclasts (direct) Ca2+ reabsorption (direct) Conversion of vitamin D In kidney In bone (indirect) Osteoblasts In bone Ca2+ reabsorption In kidney.

Hormones in the pancreas

Islets of Langerhans

  • Glucagon 
  • Somatostatin 
  • Insulin

Somatostatin (endocrine and paracrine functions)

  • first discovered in hypothalamic extracts identified as a hormone that inhibited secretion of growth hormone, a paracrine manner to inhibit the secretion of both glucagon and insulin. Somatostatin (endocrine and paracrine functions) suppresses pancreatic exocrine secretions.

Insulin and Glucagon

  • Antagonistic hormones that regulate the glucose concentration in the blood Insulin and Glucagon Beta cells of the pancreas are stimulated to release insulin into the blood. 
  • Promoting the cellular uptake of glucose (except brain cells) 
  • Slowing glycogen breakdown in the liver 
  • Promoting fat storage 
  • Inhibit the conversion to glucose

Insulin & Glucagon 

  • The liver takes up glucose and stores it as glycogen. 
  • Body cells take up more glucose. 
  • Blood glucose level declines to set point; a stimulus for insulin release diminishes.
  •  STIMULUS: Rising blood glucose level (for instance, after eating a carbohydrate-rich meal) 
  • Homeostasis: Blood glucose level (about 90 mg/100 mL) Blood glucose level rises to set point; a stimulus for glucagon release diminishes. 
  • STIMULUS: Dropping blood glucose level (for instance, after skipping a meal) Alpha cells of the pancreas are stimulated to release glucagon into the blood. 
  • The liver breaks down glycogen and releases glucose into the blood. 

Diabetes Mellitus 

  • The best-known endocrine disorder – is marked by high blood glucose. 
  • Diabetes, from the Greek diabase in, to pass through, refers to this copious urination Mellitus, from the Greek meli, honey, refers to the presence of sugar in the urine.
  •  Fat becomes the main substrate for cellular respiration Îthreatening life by lowering blood pH.

Diabetes Mellitus

  • Type I diabetes mellitus (insulin-dependent diabetes) Is an autoimmune disorder in which the immune system, destroys the beta cells of the pancreas usually appears during childhood  

Type II diabetes mellitus (non-insulin-dependent diabetes) 90% of people with diabetes have type II

  • (non-insulin-dependent diabetes) reduced responsiveness of target cells due to some change in insulin receptors deficiency of insulin heredity; excess body weight and lack of exercise
  • STIMULUS: Dropping blood glucose level (for instance, after skipping a meal) Alpha cells of the pancreas are stimulated to release glucagon into the blood.
  • The liver breaks down glycogen and releases glucose into the blood. 

 Diabetes Mellitus 

  • The best-known endocrine disorder – is marked by high blood glucose. 
  • Diabetes, from the Greek diabase in, to pass through, refers to this copious urination
  • Mellitus, from the Greek meli, honey, refers to the presence of sugar in the urine.
  •  Fat becomes the main substrate for cellular respiration Îthreatening life by lowering blood pH.

 Diabetes Mellitus

  • Type I diabetes mellitus (insulin-dependent diabetes) Is an autoimmune disorder in which the immune system, destroys the beta cells of the pancreas usually appears during childhood  

  The adrenal glands

  •  Are adjacent to the kidneys – Are made up of two glands: the adrenal medulla and the adrenal cortex

Adrenal Hormones: Response to Stress 

  • Stress and the adrenal gland Spinal cord (cross-section) 
  • Nerve signals Nerve cell Releasing hormone 
  • Stress Hypothalamus Anterior pituitary 
  • Blood vessel 
  • ACTH 
  • Adrenal gland 
  • Kidney 

The adrenal medulla secretes epinephrine and norepinephrine. 

  • Adrenal cortex secretes mineralocorticoids and glucocorticoids. 

Effects of epinephrine and norepinephrine: 

  1. Glycogen broken down to glucose; increased blood glucose 
  2. Increased blood pressure 
  3. Increased breathing rate 
  4. Increased metabolic rate 
  5. Change in blood flow patterns, leading to increased alertness and decreased digestive and kidney activity 

Effects of mineralocorticoids: 

  1. Retention of sodium ions and water by kidneys 
  2. Increased blood volume and blood pressure 

Effects of glucocorticoids: 

  1. Proteins and fats are broken down and converted to glucose, leading to increased blood glucose 
  2. The immune system may be suppressed (a) Short-term stress response (b) Long-term stress response Nerve cell 

The Endocrine System

  • THE ENDOCRINE SYSTEM: Although often overshadowed by the brain and nerves, the Endocrine system is also involved in the information business.
  • Hormones carry essential messages that have far-reaching effects.
  • They control body processes at every level, from energy uptake of a single cell to the whole body’s rate of growth and development.
  • There are 50 hormones, which are the body’s chemical messengers and they are made by 12 different Endocrine glands.
  • These glands have no ducts but secrete their hormones directly into the blood, which means they reach every cell in the body.
  • Hormones affect certain target tissues or organs and regulate their activities.

The Endocrine system sends hormones through the Circulatory system to control and coordinate body functions in much the same way as the nervous system uses tiny electrical signals. 

  • The Endocrine system and the Nervous system work together to integrate with the brain and complement each other, but they tend to work at different speeds. 
  • Nerves respond within split seconds but their action soon fades,
  • Some hormones have longer-lasting effects and act over hours, weeks, and years.
  • Hormones regulate processes such as
  • The breakdown of chemical substances in the metabolism of what we eat and drink.
  • Fluid balance and urine production. 
  • The body’s growth and development.  
  • Sexual reproduction. 

THE 12 PARTS OF THE ENDOCRINE SYSTEM

  • The hypothalamus and the pituitary gland are part of the diencephalon region of the brain.
  • The hypothalamus connects the nervous system to the endocrine system.
  • It receives and processes signals from other brain regions and pathways and translates them into hormones, the chemical messengers of the endocrine system.
  • These hormones flow to the pituitary gland, which is connected to the hypothalamus by the infundibulum.
  • Some hormones are stored in the pituitary stores for later release; others spur it to secrete its hormones.
  • The hormones released by the pituitary gland and the hypothalamus control the other endocrine glands and regulate all major internal functions.

The thymus gland produces progenitor cells, which mature into T-cells (thymus-derived cells).

  • The body uses T-cells to help destroy infected or cancerous cells.
  • T-cells created by the thymus also help other organs in the immune system grow properly.
  • These cells are so vital, they are often donated to those in need.
  • The Thymus gland is the primary donor of cells for the lymphatic system, much as bone marrow is the cell donor for the cardiovascular system.

THE ADRENAL GLANDS REGULATE SUBSTANCE LEVELS IN THE BLOOD AND RELEASE “FIGHT-OR-FLIGHT” HORMONES

  • The adrenal glands are pyramid-shaped organs that sit at the top of each kidney.
  • Each adrenal gland consists of two structures: an outer adrenal cortex and an inner adrenal medulla.
  • The adrenal cortex is a network of fine connective tissues that makes up most of the gland.
  • It secretes a range of steroid hormones.
  • Cortisol manages protein and glucose levels.
  • Aldosterone adjusts our levels of water and salt.
  • Androgens and estrogens are secreted by the adrenal cortex in small amounts by both sexes.
  • The adrenal medulla (inside the gland) produces epinephrine and norepinephrine (NE).
  • These chemicals promote “fight-or-flight,” the body’s initial response to stress.
  • The left kidney is located slightly higher than the right kidney due to the larger size of the liver on the right side of the body.

2 HORMONES MADE BY THE KIDNEYS

  • Vitamin D is essential for several different functions in the body.
  • Most of the vitamin D that is in the blood is inactive and it is modified by the kidney and other tissues to activate it.
  • Active vitamin D stimulates the uptake of calcium from food, is important for the maintenance of healthy bones, and also helps to regulate the response of the immune system to infection.
  • Erythropoietin is produced when oxygen levels in the blood are low.
  • It acts in the bone marrow to stimulate the production of mature red blood cells and to maintain healthy oxygen levels in our tissues.

SEX GLANDS AND HORMONES

  • The main sex glands are the ovaries in females and testes in males.
  • The sex hormones they produce stimulate the production of eggs and sperm respectively and influence the early development of the embryo into a boy or girl.
  • After birth, the circulating levels remain low until puberty.
  • Then, in males, the testes increase their output of androgens (male sex hormones), such as testosterone.
  • In females, the ovaries produce more estrogens and progesterone.

THE PINEAL GLAND

  • The pineal gland is small and pine cone-shaped, (which is how it got its name) located at the back of the diencephalon region in the brain.
  • At night, in the absence of light, the pineal gland secretes the hormone melatonin.
  • Melatonin regulates the body’s sleep patterns in both circadian (daily) and seasonal patterns.
  • In the morning, when light hits the eye, photoreceptors in the retina send signals to the pineal gland, which then decreases melatonin production and we wake up.

MASTER GLAND

  • The pituitary is the most influential gland in the endocrine system.
  • It is two distinct glands in one. Its front or anterior lobe manufactures 7 major hormones and releases them into the bloodstream.
  • Behind it is the posterior (back) lobe which receives its two main hormones from the hypothalamus, which lies above it, and then it releases 3 hormones, as shown.

PITUITARY GLAND 

  • The Hypothalamus Sends Hormones to the Pituitary Gland to Control the Endocrine System

THE THYROID AND PARATHYROID GLANDS INCREASE METABOLISM AND REGULATE CALCIUM LEVELS

THYROID GLAND

  • The thyroid gland sits in the throat region, just below the larynx, served by large arteries with many branches and a dense network of capillaries.
  • The hormones it secretes, travel in the bloodstream throughout the body to Increase metabolism.
  • Regulate glucose use.  
  • Protein synthesis.  
  • Nervous system development. 
  • It also releases Calcitonin, which helps maintain blood calcium homeostasis by causing calcium to be removed from the blood and deposited into bones when blood (calcium) levels are too high.

Parathyroid Glands

  • On the posterior (back) surface of the thyroid sit much smaller, separate glands: the parathyroids.
  • Typically there are four parathyroid glands, a superior and inferior pair on the left and right sides of the thyroid.
  • They secrete parathyroid hormone (PTH), which stimulates bones to release calcium into the blood when blood (calcium) levels are low.
  • PTH also causes the kidneys to reduce calcium secretion into urine to further elevate calcium levels in the blood.
  • Together, calcitonin and PTH act in complementary ways to maintain blood calcium homeostasis, which is one of the most tightly controlled physiological parameters in the body.

Iodine is an element that’s required for the thyroid gland to produce thyroid hormones.

  • Since the body does not produce iodine on its own, it needs to come from dietary sources, and striking the right balance is key.
  • The Importance of Iodine When you consume iodine, it is quickly absorbed and entered into your bloodstream.
  • Your thyroid, which has tiny cells that capture the circulating iodine, takes in and oxidizes it so it can begin to be used to create T3 and T4—thyroid hormones that make their way throughout the body to regulate metabolism and ensure healthy functioning of the heart, brain, and other organs. 

GUT HORMONES

  • The gut hormones work in association with the gut’s extensive nervous system (enteric nervous system) and play a coordinating role in:
  • The control of appetite 
  • The digestion of food 
  • The regulation of energy balance 
  • The maintenance of blood glucose levels.
  • The gut continuously sends information to the brain regarding the quality and quantity of the food that is consumed.

THE ROLE THAT SOME OF THESE HORMONES PLAY IS OUTLINED BELOW:

  • Ghrelin is produced in the stomach, and its function is to tell the brain that the body has to be fed.
  • It increases appetite.
  • Gastrin is produced in the stomach when it is stretched.
  • It stimulates the release of gastric juice rich in pepsin and hydrochloric acid.
  • Secretin is produced in the duodenum and has the effect of stimulating the pancreas to produce alkaline secretions as well as slowing the emptying of the stomach.
  • Cholecystokinin (CCK) is produced in the duodenum.
  • It reduces appetite, slows down the emptying of the stomach, and stimulates the release of bile from the gall bladder.
  • Peptide YY (PYY) is produced in the last part of the small intestine known as the ileum as well as parts of the large intestine.
  • It plays a role in slowing down the passage of food along the gut, which increases the efficiency of digestion and nutrient absorption after a meal.
  • Glucagon-like peptide 1 (GLP-1) is produced in the small intestine and colon and has multiple actions including inhibition of gastric emptying and appetite as well as the stimulation of insulin release.

PANCREAS – A DUAL-PURPOSE GLAND

  •  The Pancreas Regulates Blood Sugar Surrounded by enzyme-producing acini cells,

The tiny pancreatic islets contain three types of cells: alpha, beta, and delta.

  • The secretions of the latter help regulate insulin and glucagon production.
  • It is also a part of the digestive system.
  • It excretes pancreatic juice into the small intestine via the pancreatic duct.
  • Scattered within the pancreas there are also tiny cell clusters called pancreatic islets (or islets of Langerhans) that release hormones into the bloodstream.
  • These islets make up less than 2% of pancreatic tissue, but their specialized cells regulate blood glucose levels (or blood sugar).
  • When blood sugar is low, alpha cells in the islets release glucagon.
  • Glucagon spurs the liver to break down glycogen and release more glucose into the blood.
  • When blood sugar is high, beta cells in the islets release insulin, which increases glucose reuptake.

LIST OF ENDOCRINE GLAND / MAJOR HORMONES / PRIMARY TARGET ORGANS

Endocrine gland     Major hormones                     Primary target organs 
Adipose tissue       Leptin                                       hypothalamus 

                                  

Adrenal cortex  Glucocorticoid     liver,      muscle 
Aldosterone                        kidneys 
Adrenal medulla        Epinephrine                     heart, blood vessels 
Heart                         Atrial natriuretic hormones            kidneys 
Hypothalamus    Releasing and inhibiting hormones  pituitary 
Small intestine                Secretin, cholecystokinin                  stomach,                       liver, pancreas,        
Islets of Langerhans         Insulin                                   Insulin                                   glucagonfat, muscle, brain liver,                                        fat Kidneys 
Kidney erythropoietin bone-marrow 
Liver                                      Somatomedins                                       cartilage  
Ovaries                estradiol, progesterone repro. tract, mammary glands 
Parathyroid glands, Parathyroid hormone bone, small intestine, kidneys 
Pineal gland                Melatonin                                                 hypothalamus, 

ant. Pituitary,

Pituitary, anterior Trophic hormones endocrine glands
Pituitary, posterior Antidiuretic hormone kidney, blood vessels 
Pituitary, posterior Oxytocin uterus, mammary glands
Skin 1,25-dihydroxy vitamin D3 small intestine
Stomach Gastrin Stomach
Testes Testosterone prostate, seminal vesicles

 

ThymusThymosin lymph nodes
Thyroid gland T3, T4, calcitoninMany

Exocrine and Endocrine Glands

  • Exocrine Glands and Endocrine glands Exocrine Glands:
  • Secrete into a duct and to the outside of a body surface
  • Examples: sweat, tear, saliva 

Endocrine Glands:

  • Secrete (hormone) into the blood Hormone circulates in the blood and acts at target organs where hormone receptor is expressed 

Examples: insulin 

  • Exocrine and Endocrine glands: Endocrine
  • Exocrine Liver: IGF Bile Pancreas Pancreatic juice insulin, glucagon, PP

Chemical Structure of Hormones

  1. Amines (amino acid derivatives) Tyrosine derived: epinephrine, thyroid hormones Tryptophan derived: melatonin 
  2. Polypeptides Insulin, leptin, ADH 
  3. Glycoproteins FSH, LH 
  4. Steroids (cholesterol derived) Glucocorticoids, testosterone, vitamin D

Mechanisms of Actions of Hormones

 All hormones act by binding to their receptors 

  • Some receptors are located on the cell surface ƒ Polar hormones (insulin, leptin) 
  • Some receptors are located in the cytoplasm ƒ Lipophilic hormones (steroids, thyroid hormones) 
  • Some receptors are located in the nucleus ƒ Lipophilic hormones (TZDs, Fibrates)

Assay and Measurement of Hormones

  •  Bioassay Chemical assay Radioimmunoassay (1977 Nobel prize) 
  • Receptor binding assay (Scatchard plot)
  • The action of nuclear hormones Actions of PPARγ, a nuclear hormone receptor

Regulation of hormone secretion: 

A simple feedback loop 

↑ Blood glucose 

↓ β cells in the pancreas 

↓ ↑ Insulin secretion 

↓ ↑Uptake of blood glucose 

↓ blood glucose Liver Muscle Fat Glucose Glucose 

↓ ↓ Glycogen Triglyceride

Two general principles of hormone action

  1.  Acts on cells containing the receptor 
  2. Action is regulated by a feedback mechanism

Leptin: a new hormone from fat 

  • Made in the adipose tissues 
  • A polypeptide of 167 amino acids 
  • Product is secreted into the blood 
  • Its receptor is found in many tissues 
  • Leptin deficiency causes obesity, infertility, and many other 
  • complications.

Conditions List of 33 Critical Illness 

BLOOD TESTS (Normal value and its importance)

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