Endocrinology Flashcards
Define hormone
Any substance found in very small along in one specialised organ or group of cells carried to another organ upon which it has a specific physiological effect
Name 7 key endocrine organs
Hypothalamus Pituitary Thyroid Parathyroid Adrenal Pancreas Gonads
What are the 3 broad ways hormones act on the body
To enable and promote development of physical, sexual and mental characteristics
To keep certain physiological parameters constant
To enable and promote the adjustment of physiological adaptations
2 ways to class a hormone based on how it acts
Effector
Tropic
What are the 4 main structural types of hormone
Peptide hormone
Steroid hormones
Amino hormones
Arachidonic acid derived
What are steroids
Lipid hormones derived from cholesterol
Not water soluble
How are steroid hormones transported
In the blood bound to plasma proteins
What are amine hormones derived from
Tyrosine or tryptophan
What kind of hormone is dopamine
Amine
What are are arachidonic acid derived hormones synthesised from
What response are they important in
Linoleic acid
Inflammatory responses
What do NSAIDs do
They are Non Steroidal Anti Inflammatory Drugs
They inhibit arachidonic acid derived hormones
What is 5-HPETE
Arachidonic acid 5-hydroxyperoxidase
What is 5-LO
5-lipoxygenase
What directs peptide hormones to the secretory pathway in the cell
What happens when it reaches the ER
The N terminal sequence
This sequence is cleaved from the protein hormone, activating the hormone
What must happen for a pre hormone to become a hormone
The signal peptide sequence must be removed from the pre hormone leaving only the active hormone
How is a hormone formed from a preprohormone
The signal peptide must be removed, then the pro sequence must be removed, leaving only the hormone
What is the RF-amide family
Peptide hormones that require addition of an amide group at the carboxyl terminus to become active
Where is kisspeptide secreted
What does it do
In the arcuate and anteroventral periventricular regions of the hypothalamus
Stimulates secretion of gonadotrophin releasing protein (GnRH)
What is GnRH
Gonadotrophin releasing hormone
What is GnIH
Gonadotrophin inhibitory hormone
Where is GnIH produced
What action does it have
Paraventricular and dorsomedial regions of the hypothalamus
Inhibits release of gonadotrophin hormones from the pituitary
How do hormones signal via the GPCR pathway
Hormones bind to GPCR to activate G proteins which stimulate/ inhibit intracellular adenylyl cyclase
Stimulating adenylyl cyclase increases [cAMP] which activates PKA which alters cellular activities by phosphorylation
Describe hormone signalling via the DAG/IP3 pathway
Hormones bind to GPCR which activate G proteins to stimulate phospholipase C.
Phospholipase C converts PIP2 to IP3 and DAG
IP3 stimulates Ca2+ release from internal stores which binds to calmodulin, activating Calmodulin Activated Protein Kinase
What is the common domain structure of nuclear receptors
3 domains:
AF1 (an activation domain)
Zn2+ finger (a DNA binding domain)
Ligand binding/ dimerisation domain
How do lipid soluble hormones act on cells
They pass freely through the PM and bind to receptors in the cytoplasm
Ligand binding allows the receptor to dissociate from the heat shock receptor and to enter the nucleus, bringing about changes to gene transcription
Can hormone/ receptor complexes stimulate responses at the cell membrane
Eg?
Yes
T3
What links the hypothalamus and pituitary
A portal system links the hypothalamus to the anterior pituitary
What is the neural connection from the anterior pituitary to the hypothalamus
What about for the posterior pituitary
There is no direct neural between the anterior pituitary and the hypothalamus
The nerve fibres from the paraventricular and supraoptic nuclei pass directly to the posterior pituitary where they secrete the hormones the contain into the blood stream
Which parts of the hypothalamus contain oxytocin and vasopressin
What else does this part contain
The paraventricular nucleus ( to be secreted from posterior pituitary)
Neurons that regulate ACTH and TSH secretion
True or false
The hypothalamus helps regulate our rhythms
True it helps regulate many seasonal and circadian rhythms
What is the neurohypophysis
Posterior pituitary
What is the other name for the anterior pituitary
Adenohypophysis
Is the posterior pituitary part of the brain
Yes
Embryologically it is a down growth from the brain
What hypothalamic nerves doe the neurohypophysis contain
Paraventricular and supraoptic
What is the arrangement of the supraoptic and paraventricular nerves
Where are the hormones made
The cell bodies are in the hypothalamus and the nerve endings are in the posterior pituitary
Hormones are made in cell body and transported to nerve endings for storage in vesicles. They are released from here directly into the bloodstream
What are the hormones released from the neurohypophysis
ADH
oxytocin
Is the anterior pituitary part of the brain
No - there are no nerve fibres travelling from the hypothalamus
How does the hypothalamus communicate with the anterior pituitary
Via the hypophyseal portal vessels
Neurosecretory cells in the hypothalamus secrete releasing hormones into the primary capillary plexus which are delivered to the anterior pituitary
Is the release of hormones from the hypothalamus to the anterior pituitary constant
No it is pulsatile
Give 5 evidence for the control of anterior pituitary secretions by hypothalamic releasing hormones
1) lesions in the hypothalamus produce atrophy of some endocrine glands, similar to that when the anterior pituitary
2) electrical stimulation of hypothalamus evokes secretion of anterior pituitary hormones
3) transaction of the pituitary stalk results in atrophy of some endocrine glands
4) transplantation of the anterior pituitary to another site does not give endocrine function but if a blood supply connects to the hypothalamus, function is restored
5) addition of purified hypothalamic releasing hormones to pituitary explants in culture results in secretion of anterior pituitary hormones
How long is a circadian rhythm cycle
24 hours
What is the periodicity of a pulsatile
30 mins to 2 hours
How does the release of sex hormones vary
According to breeding seasons not the oestrous cycle
What are the 2 general methods for hormone production regulation
Negative feedback
Positive feedback
How are hormones usually measured
Immunoassays
1 immunoassay that uses colour change
1 that used a radio scope
Enzyme immunoassays
ELISA
EIA
RIA
What is the competitive ELISA method
The sample containing the hormone to be measured is mixed with a fixed amount of the same hormone labelled with an enzyme
The greater the amount of unknown hormone in the sample, the greater the competition with the labellled hormone for binding to the well
The higher the hormone concentration in the original sample the lower the visual signal
What happens for both types of ELISA in data collection
Standard curve is generated using pure hormone at known concentration
Comparison with unknown samples must be in the linear range of the standard curve
Give the method for a general ELISA
The sample with an unknown amount of hormone is immobilised in the wells of a microtiter plate via an antibody
A detection antibody covalently linked to an enzyme (eg peroxidase) is added forming a complex with the hormone
Between each step the plate is washed to remove any proteins that are not specifically bound
The antibody/ hormone complex is detected by adding an enzymatic substrate to produce a visible signal
The higher the hormone concentration in the original sample, the higher the visual signal
True or false
The adrenal gland is structurally and functionally 3 endocrine organs
False - it is functionally 2 endocrine organs
The outer cortex secretes glucocorticoids, mineralcorticoids and sex steroids
The inner medulla secreted the catecholamines adrenaline and noradrenaline
What are adrenal steroids derived from
Cholesterol
What is the principal glucocorticoid
What is the principal mineralocorticoid
Cortisol
Aldosterone
Describe regulation of adrenal gland secretions
Hypothalamic neurons released corticotrophin releasing hormone (CRH) into the portal system to stimulate pituitary corticotrophs to release ACTH into the circulation
ACTH stimulates glucocorticoid and sex hormone production from the adrenal cortex
ACTH DOES NOT regulate mineralocorticoid or catecholamine secretion
What is ACTH
Adrenocorticotrophic hormone
Which hormone causes skin pigmentation
ACTH
What is a primary adrenal insufficiency
What does this mean for hormone production
When there is a problem with the adrenal gland directly
Increased ACTH
Decreased glucocorticoids, androgens and mineralocorticoids
Why does ACTH production increase in primary adrenal insufficiency
Less glucocorticoids are produced as the actual adrenal gland is abnormal but the pituitary is normal so ACTH won’t drop
But usually there is a negative feedback loop, whereby glucocorticoids inhibit ACTH production
With reduced glucocorticoids, the negative feedback is lost and ACTH production increases
What is secondary adrenal insufficiency
What happens to hormone production
When there is a problem with the hypothalamus/ pituitary
Decreased ACTH, therefore decreased glucocorticoids and androgen
Mineralocorticoids remain normal
This is because ACTH does not affect mineralocorticoid production
What is ACTH derived from
Proteolytic processing of POMC
What is POMC
Pro-opiomelanocortin
What regulates aldosterone
What is the main action of aldosterone
Regulated by renin-angiotensin system and by plasma levels of Na and K
Conservation of body sodium by stimulating reabsorption game sodium in the kidney in exchange for potassium
What is the main glucocorticoid in humans and in other animals
Humans- cortisol
Animals- corticosterone
Discuss the circadian rhythms of plasma cortisol
Cortisol levels are highest in the morning and decline during the day
This reflects the patterns of ACTH secretion by the anterior pituitary
This probably reflects the body’s response to low blood glucose after overnight fasting
Why is it important to understand the circadian rhythms of cortisol
Cortisol replacement therapy in clinical treatment
6 key physiological actions associated with cortisol
Starvation Inflammation Immune system Pregnancy The CNS the cardiovascular system
Tell me about cortisol and starvation
Cortisol is a glucocorticoid and as the name suggests it is associated with glucose levels:
It raises blood glucose during fasting/ starvation and protects liver glycogen reserves
What’s up with cortisol and inflammation?🤷🏿♀️
Cortisol inhibits the synthesis of inflammatory substances (eg NO and prostaglandins)
Cortisol derivatives are used medically to reduce inflammations and swellings in joints
Is inflammation normal?
What causes inflammation?
It is a normal response at the site of infection
Caused by NO, prostaglandins and leukotrienes secreted from immune cells
What are cellular immune responses mediated by
interleukin production
What do interleukins promote secretion of
CRH
ACTH
cortisol
How does cortisol interact with interleukins
Inhibits secretion of interleukins by immune cells, this creating a negative feedback loop
How does cortisol affect the foetus (not in detail)
Late in gestation cortisol is secreted by the fetal adrenal gland in preparation for birth
Give the 7 effects of cortisol on the foetus to prepare it for birth
- Production of lung surfactant
- Disposition of glycogen in the liver
- Allows The intestinal tract to secrete digestive enzymes and absorb nutrients
- acid secretion by the stomach
- increased filtration rate in kidney
- T4 converted to T3
- in sheep, it stimulates steroid secretions from the placenta into the mother to initiate birth
How do cortisol and the CNS interact
As cortisol can easily cross the blood brain barrier it can alter mood
Jet lag is also caused by circadian production of cortisol being out of synch with real time
How does cortisol interact with the cardiovascular system
Permissive for vasoconstriction actions of catecholamines
Important in maintaining blood pressure
Stimulates erythropoietin synthesis to increase RBC production
What kind of responses are associated with the adrenal medulla
It is part of the SNS - fight or flight
secretes catecholamines in response to stress
Short lived responses
Give 9 actions of catecholamines
Stimulate heart rate Increased heart contractility Increased cardiac output Increased systolic pressure Reduced diastolic pressure Piloerection Reduced gut motility Increased breakdown of glycogen to glucose in the liver
What causes the release of catecholamines
SNS stimulation of chromaffin cells
What can cause hyperadrenocorticism
Adrenal gland tumour
Increased ACTH
Increased CRH
Exogenous corticosteroid treatment
What are symptoms of hyperadrenocorticism (7)
Weight gain
Rosy cheeks
Skin pigmentation (if ACTH is increased eg in Cushing’s syndrome)
Purple abdominal striations
Capillary fragility
Immunosuppression
Glucose intolerance, hyperglycaemia and insulin resistance
How can Cushing’s be treated
Removal of adrenal gland
What is the most common endocrine disorder in dogs
In which dogs is it particularly common
What is the usual cause
Canine Cushing’s syndrome
Poodles
Boxers
Dachshunds
80% caused by pituitary tumour
What are the symptoms of canine Cushing’s
Pot belly due to hepatomegaly and abdominal muscle weakness
Polyuria and polydipsia and polyphagia
General muscle wasting
Discuss equine Cushing syndrome (4)
Less common than in dogs
Excessive hairy coat
Polyuria/ polydipsia
Muscle wasting
Sweating
What is Addison’s Disease
Primary hypoadrenocorticism
Which results in deficiency of both glucocorticoids and mineralocorticoids
What causes Addison’s syndrome
Destruction of adrenals
Autoimmune reaction or inflammatory disease
Haemorrhage
What causes secondary hypoadrenocorticism
what does it result in
Lack of ACTH
Deficiency of glucocorticoids only
What are the symptoms of Secondary hypoadrenocorticism
What do they depend on
What if ACTH production isn’t impaired
It depends on whether aldosterone is lacking
If both aldosterone and cortisol is lacking it leads to hypotension and eventual death.
Tiredness and weakness
Vomiting
Skin pigmentation
No pigmentation; loss of body hair in females, in males get sex hormones from their testes
What causes congenital adrenal hyperplasia
How does the body try to compensate
Lack of enzyme involved in cortisol production (21-hydroxylase or 11-β-hydroxylase)
Increase CRH-ACTH levels
What does congenital adrenal hyperplasia lead to if caused by 21-hydroxylase deficiency
Excessive production of sex steroids
Masculinisation of female foetus
Decreased production of mineralocorticoids which could mean life threatening salt loss
How much of congenital adrenal hyperplasia is caused by each enzyme deficiency
21-hydroxylase : 95%
11-β hydroxylase : 5%
What does congenital adrenal hyperplasia caused by 11-β hyroxylase deficiency
Excessive deoxycorticosterone which has mineralocorticoid activity
This leads to life threatening hypertension
How does congenital adrenal hyperplasia affect males vs females
Females: in uterus there is clitoral hypertrophy, fusion of labia and urogenital opening at the base of pseudo-phallus
Treaty by surgical reconstruction of genitalia
Males: precocious puberty
Where is the thyroid
Attached to the trachea just below the larynx
True or false
The blood supply to the thyroid has a poor, tortuous blood supply
False
It has a rich blood and autonomic never supply
What are the 3 hormones secreted by the thyroid
Thyroxine (T4)
Tri- iodothryonine (T3)
Calcitonin
What are the iodine containing thyroid hormones attached to
Where are they stored
Thyroglobulin
In the colloid material
What are C cells
What is their function
Parafollicular cells in the thyroid
Secrete calcitonin
What does calcitonin do
Regulates plasma Ca2+ levels
What controls blood supply to the thyroid
Nerves
What regulates thyroid secretions
The hypothalamic pituitary axis
Describe the hypothalamic - pituitary axis regulation of the thyroid
TRH from the hypothalamus stimulates the anterior pituitary to release TSH
TSH acts on the thyroid to increase T4/T3
What is TRH
Thyrotrophin releasing hormone
What is TSH
Thyroid stimulating hormone
Which is the most potent thyroid hormone
T3
what is DI
what is its function
where is it found
Deiodinase enzyme
Converts T4 to T3
It is found in target tissue and also in the pituitary to facilitate negative feedback (
How is T4 formed
Iodine is attached to tyrosine to produce MIT and then again to produce DIT
DIT is coupled with another DIT to produce T4
How is T3 made
Iodine is added to tyrosine to form MIT and then again to form DIT
DIT is coupled with MIT to form T3
How is T3 formed from T4
Monodeiodination
(Removal of an iodine)
Depending on which iodine this can form either active T3 or reverse T3
How is iodide taken into the thyroid epithelial cells from the blood
By SLC5A5 (a sodium-iodide symporter)
TAKEN UP AS IODIDE NOT IODINE
How is iodide turned into iodine in the thyroid epithelial cells
By a peroxidase
What happens to iodine that has just entered the thyroid colloid
It is added onto exposed Tyrosine residues on thyroglobulin
What happens to thyroglobulin after iodine bonding to tyrosine residues
It is taken into the epithelial cells via endocytosis
What happens to thyroglobulin once it emerges into the epithelial cells
Broken down by lysosomes to release T3 and T4 into the circulation
How does TSH increase T3 and T4 release
It stimulates iodide uptake via the SLC5A5,
increases iodide oxidation to iodine,
increases endocytosis of thyroglobulin
and stimulates secretion of T3/T4
How does T3 act
Binds to specific nuclear receptors to alter transcription
3 things thyroid hormones affect
What is the overall function
Whole body growth
Basal metabolic rate
Cardiac output
Overall: increase substrates for oxidative respiration in cells
What is the mechanism of T3 on peripheral thermogenesis
Stimulates Na/K pump, glycerol phosphate dehydrogenase (GPDH), uncoupling protein 3 (UCP3), and SERCA
To generate heat
Why does T3 stimulate UCP3
Uncoupling the electron transport chain produces heat instead of ATP
What is SERCA
Smooth endoplasmic reticulum Ca2+ ATPase
What are the mechanisms of thyroid hormones in central thermogenesis
T3 acts on ventromedial hypothalamus (VMH) to inhibit AMPK and increase SNS signals to brown adipose to generate heat via UCP1
Why is brown adipose so high in babies
For thermogenesis
Muscular thermogenesis is not fully developed yet so T3 must act on brown adipose
What used to be called cretinism
Lack of thyroid hormone during late fetal life and early post natal development that resulted in severe mental retardation
Why can hypothyroidism be caused by
Iodine deficiency
Thyroid disease (eg autoimmunity (Hashimoto’s Disease)) - primary hypothyroidism
Lack of TSH - secondary hypothyroidism
congenital absence of thyroid
Give 6 symptoms of hypothyroidism
Weight gain Goitre Cold extremities Lethargy Muscle weakness Reduced cardiac output and slow pulse
How might you treat hypothyroidism
Administer Levothyoxine (T4 stereoisomer)
What can hyperthyroidism be caused by
Overactive thyroid
Autoimmune - anti bodies bind to TSH receptor and activate it (Graves’ disease)
True or false:
Hyperthyroidism is more common in men
False
It is 10x more common in women
Give 9 symptoms of hyperthyroidism
Weight loss Sweating Goitre Agitated/ nervous Fast heart rate and atrial fibrillation Muscle weakness Rapid growth/ bone maturation in children Opthalmopathy (bulging/staring eyes) Infertility/ lack of periods
Treatment for hyperthyroidism
Administer anti thyroid drugs then Levothyroxine to replace the hormones at the correct levels
Surgery
Destruction of thyroid by radio-iodine treatment
What is the most common endocrine condition in cats (especially older cats)
What is it often caused by
What are symptoms
Hyperthyroidism
Benign thyroid adenoma
Weight loss
Rapid heart loss
Vomiting/ diarrhoea
Increased water constipation
How do you treat feline hyperthyroidism
Block/ replacement therapy to block hormone production and give oral thyroxine
Surgery
Destruction of thyroid by radiotherapy
When is Human fetal growth greatest
Between 16-20 weeks of gestation
Describe how rates of growth vary throughout human life
Increases steadily in gestation, reaching a peak at 20 weeks then decreases until birth
After birth, growth velocity declines after birth until pubertal growth spurts
True or false
The earlier the growth spurt at puberty the shorter the final height
True
3 factors involved in growth
Genetic
Environmental
Physiological
What is the structure of growth hormone
191 amino acid polypeptide
2 disulphide bridges
What is another name for growth hormone
somatotropin
What 2 proteins is somatotropin closely associated with
Prolactin
Placental lactogens
6 factors that influence growth hormone
GHRH Arginine Ghrelin Hypoglycaemia Sleep Exercise
What is GHRH
A 44 amino acid peptide from arcuate neurons in the hypothalamus
What is the relevance of arginine stimulating GH release
It is used to clinically diagnose GH deficiency
What is the release of GH decreased by
Which of these is used to diagnose GH deficiency
Somatostatin GH via negative feedback IGF1 (via negative feedback) Lipids Age Thyroid deficiency Hyperglycaemia (used to diagnose GH deficiency)
What is somatostatin
A 14 amino acid peptide released from periventricular neurons in hypothalamus
How many amino acids in GHRH
44
Where is GHRH produced
Where is it released into and what is its effect
By arcuate hypothalamic neurons
Released into portal system to stimulate somatotropins in the anterior pituitary to produce GH
What kind of receptor is the GHRH receptor
What is the cascade
A GPCR
G proteins increase cAMP in somatotrophs
Are GH effects always direct
No
GH has direct effects in muscle, bone and adipose
But has indirect effects via IGF1 (a somatomedin)
What is the effect of GH on bones
Promotes bone growth in long bones by stimulating chondrocytes at the epiphyseal growth plate
What are the metabolic effects of growth hormone
Inhibition of glucose uptake by muscle and fat cells
Increased lipolysis
Increased sodium and fluid retention through increased GFR
increased BMR
hepatic gluconeogenesis
Reduced sensitivity to insulin
7 types of growth factor
Nerve growth factor Epidermal growth factor Transforming growth factor Fibroblast growth factor Platelet derived growth factor Erythropoietin Interleukin
Other than GH what are other hormones involved
Growth factors Thyroid hormones Gonadal steroids Glucocorticoids Insulin
How are thyroid hormones involved in growth
What happens if the thyroid is under active
They are permissive for growth and helps with maturation of the CNS
How do gonadal steroids affect growth
Systemic effect- stimulate HH release to bring about pubertal growth spurts
Increased rate of long bone growth
Local effects: sex steroids eventually trigger epiphyseal fusion to limit long bone growth
How are glucocorticoids involved in growth
Growth inhibition when present in excess
How is Insulin involved in growth
Essential for normal growth especially in utero
Give 2 growth hormone disorders
What’s the difference
Gigantism: hyper secretion of GH before puberty
Acromegaly: hyper secretion of GH in adulthood
How common is acromegaly
What is a common cause
60 per million
Pituitary tumour
What is the clinical appearance of acromegaly
Increased cartilaginous growth resulting in enlarged ears and loss, growth of jaw, enlargement of hands and feet and enlargement of tongue
What is the clinical appearance of gigantism
Normal proportions just very tall
What are pituitary dwarves
How is it treated
GH deficiency during childhood causes reduced growth with normal body proportions
Caused by a problem with the pituitary
Treated with GH injections but must use species specific GH
How is achondroplasia different from pituitary dwarfism
Achondroplasia presents with reduced growth with abnormal body proportions
Achondroplasia is caused by mutation in FGFR3
What is a joule
The work done when 1N moves 1m
What is power
1W=?
Rate of work
1W= 1J/s
How many joules in a kilocalorie
1Kcal= 4184 joules
What is BMR
Basal metabolic rate
The energy required to keep a resting awake individual alive in a thermoneutral environment
What is required for BMR (ie how many calories)
1800kcal/day
Why is the recommended guideline daily amount of calories higher than needed for BMR
To account for movement and environment temperature
What is the GDA for men, women and children
Men: 2500
Women: 2000
Children (5-10yrs): 1800
How can metabolic rate be measured
By indirect calorimetry
What is indirect calorimetry
Measuring the amount of heat generated in an oxidative reaction by determining the intake of O2 or by measuring the amount of CO2 released and translating these quantities into a heat equivalent
Describe the action of insulin and glucagon
Regulation of blood glucose
They act antagonistically: insulin promotes energy storage and glucagon decreases energy storage
What are incretins
GLP-1 and GIP
they are peptides released by the digestive tract in response to a meal and act on the islets of Langerhans To help modulate blood glucose levels
They stimulate insulin release and inhibit glucagon production
How is ATP used up in the body
25% Na/K pump 30% RNA/DNA synthesis 25% protein synthesis 10% gluconeogenesis 5% Ca2+ pump 5% muscle contraction
Where is GLP-1 released from
L cells in the GI tract
What secretes GIP
K cells in duodenum
What is the importance of incretins?
They cause insulin release before blood glucose changes as incretin release is stimulated by glucose in the GI tract not in the blood
What does anoretic mean
Appetite suppression
What does oretic mean
Appetite stimulation
What has ablation taught us about appetite
Destruction of the lateral hypothalamus (LH) in rats reduced food intake
Destruction of the ventromedial nucleus (VMN) induced hyperphagia and obesity
Who discovered leptin
What experiments did he do
Hervey (1956)
Parabiosis
Describe Hervey’s parabiosis experiments
An obese rat (with a VMN lesion) was connected to a normal rat
The normal rat stopped eating and died of starvation
Blood born satiety factor was produced in obese rat but didn’t affect it and passed into normal rat, decreasing appetite
How big is leptin
What produces if
16 kDa
White and brown adipose tissue
The level of leptin in the blood is directly proportional to what?
The amount of adipose tissue in the body
Which mice have a mutation in the leptin gene and which had a mutation in the receptor
What symptoms are common between them
Gene: (ob/ob) (obese=ob)
Receptor (db/db) (diabetes=db)
Symptoms: hyperphagia, obese, and increased risk of T2 diabetes
Can leptin cross the blood brain barrier
Yes
The ObRa (shorter leptin receptor) binds leptin and allows leptin to cross the barrier to have an effect on the hypothalamus The ObRb receptor initiates a signalling cascade
Briefly explain the parabiosis experiments with db/db and ob/ob nice
db/db mice have high leptin levels that act on normal and ob/ob mice to suppress feeding (usually ending with them dying of starvation)
Ob/ob mice do not make leptin so cannot influence feeding behaviour of normal mice
How many amino acids in Ghrelin
What is it produced by
28
P/D1 cells and ε cells
Where are P/D1 cells
Where are ε cells
What do they produce
P/D1 : fundus of the stomach
ε cells: islets of Langerhans
Produce Ghrelin
What happens to Ghrelin levels after a meal
Levels fall
How does Ghrelin act as an orectic peptide
Stimulates NPY/AgRP neurons in the hypothalamus
How does Ghrelin affect GH
Increases GH secretion from the pituitary
Which neurons in the arcuate nucleus are satiety neurons
POMC/CART
What is the key receptor in the VMH satiety centre
MC3/4R
What is the key receptor in the LH feeding centre
Y1/Y5 receptor
What does α MSH do
Acts through MC3/4 receptor to suppress feeding
What does a defective MC4 receptor lead to
Obesity
What does NPY
Acts through Y1/5 receptor to stimulate feeding
How does AgRP interact with the Mc3/5 receptor
AgRP is an antagonist if MC3/4 R
How does leptin interact with NPY/ AgRP and POMC/CART
Leptin inhibits NPY/ AgRP neurons
Leptin stimulates POMC/ CART neurons
What is the relationship between Ghrelin and insulin levels
Inverse
How do neuronal pathways affect appetite regulation
Provide information about stomach distension and food digestion via vagus nerve to the dorsal Vagal complex
What gut hormones stimulate satiety
Where are they released from
CCK (via vagus nerve)
Oxyntomodulin (OXM)
Peptide YY (PYY)
Glucagon-like peptide 1 (GLP-1)
Lower GI tract
Where is pancreatic polypeptide secreted from
What is its role
Islets of Langerhans
Stimulate satiety
4 treatments for obesity
Eat less (both in life style and via bariatric surgery)
Exercise
Restrict food absorption
Liposuction (THIS IS ONLY COSMETIC)
By How much does bariatric surgery reduce stomach volume
From 1000ml to 30ml
How is iodide pumped into follicular cells
SLC5A5 (sodium iodide symporter)
