L12: Introduction to the Endocrine system & Endocrine control of appetite Flashcards
Define homeostasis?
Dynamic equilibrium to counteract changes in the internal environment and remain stable and relatively constant
What can happen if homeostasis fails?
Disease
What are the characteristics of a control system?
- Stimulus
- Receptor
–> Detect stimuli
–> Chemoreceptors, thermoreceptors, nociceptors, proprioceptors - Control centre
–> Determines the set point
–> Analyses afferent input
–> Determines response - Effector
–> Causes change
Negative (or positive) feedback to turn stimulus off
What are the names of the pathways that take the signal to and from the control centre?
Afferent pathway–> to the control centre
Efferent pathway–> away from the control centre
Nervous system uses AP
Endocrine system uses hormones
What are biological rhythms?
Circadian rhythms (diurnal) Body clock --> suprachiasmatic nucleus Set point varies throughout the day based on cues from the external environment (light, temperature, social interaction, exercise, eating/drinking pattern)
What is jet lag?
Mismatch between your body clock and the external environment
What is responsible for setting the biological clock?
Melatonin from pinneal gland
What is important to remember when taking a blood test for cortisol?
Different levels throughout the day
Ensure you record the time taken when you take the sample
What are feedback loops?
Effector feedsback on stimulus to either enhance or inhibit stimulus
Positive and negative feedback loops
What is negative feedback?
Response reverse the direction of change
Most common
What is positive feedback?
Response changes variable even more in the direction of change
Rare
Used when rapid change is desirable e.g. childbirth, blood clotting
What is the difference between the long and short loop?
Long loop–> last hormone released feedsback on AP and hypothalamus
Short–> second hormone released feedsback on hypothalamus
What detects changes in the osmotic pressure?
Osmoreceptors in the hypothalamus
What is the difference between osmolarity and osmolality?
Osmolarity–> Number of osmoles per litre of solution (volume)
Osmolality–> Number of osmoles per Kg of solution (mass)
What is the normal range for sodium concentration?
275- 295 mOsmol/kg
Hyponatraemia –> low Na+ in the blood
How does antidiuretic hormone control body fluid homeostasis?
Increased Osmolality (high solute concentration)–> detected by osmoreceptors in hypothalamus–> Posterior pituitary secretes more ADH–> Increased resorption of H2O in kidneys–> normal blood osmolality and small amount of concentrated urine
Decrease osmolality (low solute concentration)–> osmoreceptors–> Posterior pituitary secrete less ADH–> Decreased resorption of H2O in kidneys–> normal blood osmolality with large volume of dilute urine
How is plasma glucose homeostasis maintained?
Blood glucose- 5mM Increase glucose (after eating)--> pancreas secrete insuin--> stimulates glycogenesis in liver (storage) and glucose uptake in muscle and adipose tissue (GLUT4 transporter) --> plasma glucose declines
Plasma glucose decreased–> pancreas releases glucagon–> stimulates glycogenolysis–> plasma glucose increases
What are the major endocrine organs?
Collection of glands located throughout the body
Hypothalamus, pituitary gland, pineal gland, parathyroid gland, thyroid gland, thymus, pancreas, ovaries/testes, adrenal gland,
How do you define an endocrine gland?
Ductless
Releases hormones into the bloodstream
Affect on distant targets
What else releases important hormones?
Heart (ANP/BNP) Liver (IGF1) Stomach (Gastrin, Ghrelin) Placenta (Inhibin, Placental Lactogen) Adipose (Leptin) Kidney (Erythropoietin, Renin, Calcitriol)
What are the mechanisms of communication via hormones?
Autocrine–> Acts back on self
Paracrine–> Acts on neighbouring cells/short distance
Endocrine–> Released into bloodstream, distant target
Neurocrine–> Hormone originates in neuron, released into bloodstream to act on distant target
Compare and contrast the endocrine and nervous system?
Both capable of secreting
Both can be depolarised
Some molecules act as both hormone and NT
Mechanism of action involves interaction with specific receptors
Work in parallel to control homeostasis
Endocrine is hormones, nervous is NT
Both chemical signal and nervous also electrical
Conveyance: Endo- BS, Nervous- Synapses and axons
Endocrine slow, nervous fast
What are the different classifications of hormones?
Peptide/ polypeptide
Amino acid derivatives
Glycoproteins
Steroids
What is specific about peptide/ polypeptide hormones?
Largest group
Short chains of AA (insulin, glucagon, growth hormone)
All water soluble
What is specific about amino acid derivatives?
Synthesised from aromatic AA
- Adrenaline (tyrosine), noradrenaline (tyrosine), thyroid hormone (tyrosine), melatonin (trytophan)
Adrenal medulla hormones –> water soluble
Thyroid hormones –> lipid soluble
What is specific about glycoproteins?
Large protein molecules
Made up of subunits
Carbohydrate side chain (LH, FSH, THS)
All water soluble
What is specific about steroids?
Derived from cholesterol
Steroidogenic tissues convert cholesterol to different hormones (cortisol, aldosterone, testosterone)
All lipid soluble
How are hormones transported in the blood?
Some travel as peptides, adrenaline
Most–> bound to carrier proteins
Often specific proteins e.g. thyroid hormones–> Thyroxine-binding globulin TBG
Dynamic equilibrium–> between bound and unbound state
Free hormone + binding protein –> bound hormone
Free form is biologically active
What are the roles of carrier proteins?
Increase solubility of hormones
Increase half-life
Readily accessible reserve
What are the three factors that determine hormone levels?
Rate of production –> synthesis and secretion, highly regulated
Rate of delivery–> high blood flow to organ= deliver more
Rate of degradation–> metabolised and excreted from the body
How do hormones exert their effects?
Hormones carried in blood to target tissue
Target cells have specific receptors
Specific cellular response to hormone
What are the mechanism of action of a water soluble hormone at the target cell?
Requires second messengers
Commonly GPCR and Tyrosine kinase
How do GPCR work?
Hormone binds to receptor Dissociation of G protein α subunit Activation of effector protein Formation of second messenger Activation of protein kinase Phosphorylation of target proteins Cellular response
How does tyrosine kinase work?
Hormones bind to receptor
Dimerisation of receptor (except insulin which is already)
Autophosphorylation of specific tyrosines
Recruitment of adaptor proteins and signalling complex
Activation of protein kinase
Phosphorylation of target proteins
Cellular response
What is the mechanism of action for a lipid soluble receptor?
Hormone can diffuse through phospholipid bilayer
Different types of hormone act in different ways:
Type 1- Cytoplasmic receptor binds hormone, receptor-hormone complex enters nucleus and binds to DNA
Type 2-Hormone enters nucleus and binds to pre-bound receptor on DNA, binding relieves repression on transcription
- Receptor is bound to a specific DNA sequence called hormone response element (HRE) in promoter region of specific genes
Transcription and translation to produce new mRNA which mediates the effects of hormone–> cellular response
What causes people to become obese?
Energy intake» energy expenditure
BMI > 30kg/m2
How is our appetite controlled?
Satiety centre located in the hypothalamus
Arcuate nucleus–> appetite control
Other areas of brain involved
What are the neurones of the arcuate nucleus?
Primary neurones in arcuate nucleus
Two types
-Stimulatory–> Neuropeptide Y (NPY) and Agouti-related peptide (AgRP)–> promote hunger
-Inhibitory–> Proopiomelanocortin (POMC) yield several NT including α-MSH and β-endorphin
Primary interact with secondary in other areas of the brain and signals are integrated
What is the stimulatory signal for the hypothalamus (arcuate nucleus) when you are hungry?
Ghrelin (- hungry stomach Growling) Peptide hormone Released from wall of empty stomach Stimulates excitatory primary neurons--> stimulates appetite Inhibited by filling of stomach
What suppresses appetite from gut?
Peptide tyrosine tyrosine (PYY) Short 36aa peptide hormone Ileum and colon in response to feeding Inhibits excitatory neurons--> suppress appetite Mouse brain injection--> anorexic Human deficient--> obese
What other hormones are released from the body to control appetite? How do they work?
Leptin–> peptide hormone from adipocytes (fat cells)
–> Stimulates POMC inhibitory neuron
–> Inhibits NPY/AgRP excitatory neurons
–> Suppress appetite
–> Induces uncoupling proteins in mitochondria, energy dissipated as heat
Insulin–> Suppress appetite (similar to leptin)
Amylin–> Peptide hormone, β cells in pancreas
–> Decrease glucagon, slow gastric emptying
–>Suppress appetite
–> Pramlintide amylin analogue approved for type 2 diabetes
Draw a diagram to summarise the control of appetite?
Slide 27
Why is Leptin so important?
Jeffery Friedmann (1994)--> Obese mice Showed loss of function of Leptin gene Discovered in humans too--> obesity Injection of Leptin --> lost weight Doesn't work if Leptin administered to common obesity--> develop Leptin resistance
