L12: Introduction to the Endocrine system & Endocrine control of appetite

Question 1

Define homeostasis?

Answer 1

Dynamic equilibrium to counteract changes in the internal environment and remain stable and relatively constant

Question 2

What can happen if homeostasis fails?

Answer 2

Disease

Question 3

What are the characteristics of a control system?

Answer 3

1. Stimulus
2. Receptor
   –> Detect stimuli
   –> Chemoreceptors, thermoreceptors, nociceptors, proprioceptors
3. Control centre
   –> Determines the set point
   –> Analyses afferent input
   –> Determines response
4. Effector
   –> Causes change
   Negative (or positive) feedback to turn stimulus off

Question 4

What are the names of the pathways that take the signal to and from the control centre?

Answer 4

Afferent pathway–> to the control centre
Efferent pathway–> away from the control centre
Nervous system uses AP
Endocrine system uses hormones

Question 5

What are biological rhythms?

Answer 5

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)

Question 6

What is jet lag?

Answer 6

Mismatch between your body clock and the external environment

Question 7

What is responsible for setting the biological clock?

Answer 7

Melatonin from pinneal gland

Question 8

What is important to remember when taking a blood test for cortisol?

Answer 8

Different levels throughout the day

Ensure you record the time taken when you take the sample

Question 9

What are feedback loops?

Answer 9

Effector feedsback on stimulus to either enhance or inhibit stimulus
Positive and negative feedback loops

Question 10

What is negative feedback?

Answer 10

Response reverse the direction of change

Most common

Question 11

What is positive feedback?

Answer 11

Response changes variable even more in the direction of change
Rare
Used when rapid change is desirable e.g. childbirth, blood clotting

Question 12

What is the difference between the long and short loop?

Answer 12

Long loop–> last hormone released feedsback on AP and hypothalamus
Short–> second hormone released feedsback on hypothalamus

Question 13

What detects changes in the osmotic pressure?

Answer 13

Osmoreceptors in the hypothalamus

Question 14

What is the difference between osmolarity and osmolality?

Answer 14

Osmolarity–> Number of osmoles per litre of solution (volume)
Osmolality–> Number of osmoles per Kg of solution (mass)

Question 15

What is the normal range for sodium concentration?

Answer 15

275- 295 mOsmol/kg

Hyponatraemia –> low Na+ in the blood

Question 16

How does antidiuretic hormone control body fluid homeostasis?

Answer 16

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

Question 17

How is plasma glucose homeostasis maintained?

Answer 17

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

Question 18

What are the major endocrine organs?

Answer 18

Collection of glands located throughout the body
Hypothalamus, pituitary gland, pineal gland, parathyroid gland, thyroid gland, thymus, pancreas, ovaries/testes, adrenal gland,

Question 19

How do you define an endocrine gland?

Answer 19

Ductless
Releases hormones into the bloodstream
Affect on distant targets

Question 20

What else releases important hormones?

Answer 20

Heart (ANP/BNP)
Liver (IGF1)
Stomach (Gastrin, Ghrelin)
Placenta (Inhibin, Placental Lactogen)
Adipose (Leptin)
Kidney (Erythropoietin, Renin, Calcitriol)

Question 21

What are the mechanisms of communication via hormones?

Answer 21

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

Question 22

Compare and contrast the endocrine and nervous system?

Answer 22

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

Question 23

What are the different classifications of hormones?

Answer 23

Peptide/ polypeptide
Amino acid derivatives
Glycoproteins
Steroids

Question 24

What is specific about peptide/ polypeptide hormones?

Answer 24

Largest group
Short chains of AA (insulin, glucagon, growth hormone)
All water soluble

Question 25

What is specific about amino acid derivatives?

Answer 25

Synthesised from aromatic AA - Adrenaline (tyrosine), noradrenaline (tyrosine), thyroid hormone (tyrosine), melatonin (trytophan) Adrenal medulla hormones --> water soluble Thyroid hormones --> lipid soluble

Question 26

What is specific about glycoproteins?

Answer 26

Large protein molecules Made up of subunits Carbohydrate side chain (LH, FSH, THS) All water soluble

Question 27

What is specific about steroids?

Answer 27

Derived from cholesterol Steroidogenic tissues convert cholesterol to different hormones (cortisol, aldosterone, testosterone) All lipid soluble

Question 28

How are hormones transported in the blood?

Answer 28

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

Question 29

What are the roles of carrier proteins?

Answer 29

Increase solubility of hormones Increase half-life Readily accessible reserve

Question 30

What are the three factors that determine hormone levels?

Answer 30

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

Question 31

How do hormones exert their effects?

Answer 31

Hormones carried in blood to target tissue Target cells have specific receptors Specific cellular response to hormone

Question 32

What are the mechanism of action of a water soluble hormone at the target cell?

Answer 32

Requires second messengers | Commonly GPCR and Tyrosine kinase

Question 33

How do GPCR work?

Answer 33

``` 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 ```

Question 34

How does tyrosine kinase work?

Answer 34

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

Question 35

What is the mechanism of action for a lipid soluble receptor?

Answer 35

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

Question 36

What causes people to become obese?

Answer 36

Energy intake>> energy expenditure | BMI > 30kg/m2

Question 37

How is our appetite controlled?

Answer 37

Satiety centre located in the hypothalamus Arcuate nucleus--> appetite control Other areas of brain involved

Question 38

What are the neurones of the arcuate nucleus?

Answer 38

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

Question 39

What is the stimulatory signal for the hypothalamus (arcuate nucleus) when you are hungry?

Answer 39

``` Ghrelin (- hungry stomach Growling) Peptide hormone Released from wall of empty stomach Stimulates excitatory primary neurons--> stimulates appetite Inhibited by filling of stomach ```

Question 40

What suppresses appetite from gut?

Answer 40

``` 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 ```

Question 41

What other hormones are released from the body to control appetite? How do they work?

Answer 41

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

Question 42

Draw a diagram to summarise the control of appetite?

Answer 42

Slide 27

Question 43

Why is Leptin so important?

Answer 43

``` 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 ```