exocrine system - videos - week 3 Flashcards
adrenal glands, blood glucose conc
What is the endocrine system
- cell to cell communication via chemical messenger
- travels via circulatory system long distances between gland and target cell - cm to meters
- slow - min to days - doesn’t always take shortest route
- sustained signalling, sometimes irreversible - can’t rapidly turn signal of
What is the Endocrine axis ?
- system of communication between multiple endocrine glands
Name three examples of the endocrine axes?
- hypothalamic-pituitary adrenal (HPA)
- Hypothalamic pituitary gonadal (HPG)
- hypothalamic-pituitary-thyroid
What are the bodily functions regulated by the endocrine system?
- homeostasis eg. blood glucose - pancreatic hormones
- growth and development
- stress acute or chronic
- red blood cell production
- organ to organ communication
- circulatory and digestive system in parts
How to classify endocrine glands?
broadly into primary - inside CNS or secondary - outside CNS, in peripheral
Name central glands
hypothalamus
pineal gland
pituitary
Name peripheral glands
gonad
adrenal
pancreas
What is the only example of a direct feedback loop in the endocrine system?
heart produces ANP - blood pressure regulation
What prepares the body for the spike in glucose after having a meal?
Stomach produces ghrelin - controls appetite and body mass
How do we classify endocrine hormones?
hydrophilic - peptides, biogenic amines
hydrophobic - biogenic amines and steroid hormones
What is an example of a peptide hormone made from a single peptide chain?
Insulin
How is insulin produced?
- initially signal sequence removed
- required for traffic to the Golgi for packaging
- disulphide bonds across primary chain form a loop
- C chain removed to create a 2 peptide molecule held by disulphide bonds
- single insulin gene
- peptide fold into spiral
What does melatonin come from?
- the neurotransmitter serotonin
- produced in hour of darkness
- sleep regulation, seasonal breading
What is the best example for hydrophobic hormones?
- thyroid hormones T3 or T4 - depending on how many iodines added to 5 prime
- if present T4 - more common, weak
- if missing T3 - stronger
What other hydrophobic hormones are there?
steroid hormones
Which steroid hormones are produced from C27 cholesterol in the adrenal gland?
- glucocorticoids (cortisol - C21)
- mineralocorticoids (aldosterone - c21)
- adrenal androgens (DHEA- C19)
Which steroid hormones are produced from C27 cholesterol in the gonadal glands?
- progesterone
- androgens
- estrogens
Steroid hormones all originate from…
cholesterol via progesterone - hydrophobic ring structure
How do hydrophilic hormones actually create a cellular response?
- bind to transmembrane receptor
- includes secondary messenger/ion
- active kinase enzymes within a cell (protein kinase or lipid kinase)
- alters activity of existing proteins - quick
- alter gene expression - slow
How do hydrophobic hormones cause a cellular response?
- can pass directly though membrane
- bind to transmembrane receptor
. includes secondary messenger
. activate kinase enzymes within a cell (protein kinase or lipid)
. alters activity of existing proteins
. alter gene expression - bind to nuclear receptors
. form ligand dependent transcription factors
. regulate gene expression via histone mod
. slower but more sustained changes
. new gene could be structural or enzymatic
How many control points do direct feedback loops have?
single one
What is the best example of a direct feedback loop in mammals?
atrial natriuretic peptide (ANP)
What are first order feedback loops?
single feedback loop via a signalling centre
eg. sensory neuron - integrating center - neuron - target organ
How many control points do second order feedback loops have?
two
What’s the HPT axis?
Hypothalamus -> TRH -> anterior pituitary -> TSH -> thyroid -> T3 and T4
(negative feedback loop)
What is the function of the outer cortex of the adrenal gland?
makes the corticosteroid hormones
What is the function of the inner medulla of the adrenal gland?
- chromaffin cells
- make catecholamines (adrenaline)
- neural crest derived during Embryo development
- can make neurotransmitter
What is the neural crest?
a group of cells which migrate through the early embryo and have neural identity
- can Mae neurotransmitters
Name the layers of the adrenal gland from outer to inner
capsule
zona glomerulosa
zona fasciculata
zona reticularis
medulla
What is the capsule ?
though outer layer of the adrenal gland
What is the function of the zone glomerulosa?
- synthesis mineralocorticoids
- aldosterone
- reabsorption of Na+ ions in kidney
- increases plasma volume
- increases blood pressure
- increases secretion of K+ ions into urine
- stimulated by changes in ion conc
-> K ions sensed directly,
-> Na ions sensed indirectly
Describe the renin-angiotensin-aldosterone- system (RAAS)
- not an endocrine axis - only one gland
- fall in blood volume- blood pressure
- less blood = less sodium sensed by kidney
- increased conversion of protein to renin - enters blood
- enin converts angiotensionogen to angiotensin 1 (hormone)
- causes blood vessels to constrict
- Angiotensin 1 converted to angiotensin 2 by Angiotensin conversion enzyme (ACE)
- AT2 receptors in ZG stimulate aldosterone synthesis in adrenal gland
Is renin an enzyme of a hormone?
active enzyme
name the functions of the zone fasciculata
- synthesis glucocorticoids (cortisol)
- increases blood plasma glucose conc and NEFAs
- chronic stress response
- inhibit non-essential activities and immune system
Describe how the zone fasciculata is stimulated by the ACTH form the anterior pituitary gland (HPA axis)
- adrenal gland produces cortisol
- circulates bound to albumin or cortisol- binding globulin
- cortisol causes negative feedback on cortisol releasing hormone (CRH) from the hypothalamus
- also causes negative feedback on ACTH form pituitary gland
- also impacts metabolic inputs to hypothalamus
What is the ACTH interaction with the HPA in the zona fasciculata an example of?
third order feedback system
What is the function of the zone reticularis?
- adrenal androgens (dehydroepiandrosterone DHEA)
- metabolised to potent androgens (testosterone and estrogens) in other tissues
- pubertal development (increased DHEA)
- later life aging (declines DHEA)
- stimulated by ACTH form HPA axis
- circulates bound to albumin and SHBG
- sulphated DHEA has no affinity for SHBG and becomes water soluble
Describe the function of the medulla
- modified sympathetic ANS
- produce catecholamines (noradrenaline and also adrenaline)
- 80% adrenaline
- no endocrine control
What are chromaffin cells ?
modified neurons with no axons, neural crest derived
Where is the adrenaline stored in?
granules - sympathetic neural input causes secretion of adrenaline
Describe the conversion of noradrenaline to adrenaline
methylation by PNMT enzyme
- expression unregulated in chromaffin cells only
- phenyl ethanol-amine N-methyl transferase
(CH2)
Describe the the function fo the GPCR receptors in the adrenaline response
- alpha receptors - modulate intracellular calcium signalling, increase intracellular calc causing contraction
- beta receptors - adenyl cyclase action, cAMO prodded protein kinase activated
Describe an acute stress response
- increases blood flow, blood pressure and heart rate (alpha)
- increases blood glucose conc (beta receptor response)
- sensitising the CNS (pupil dilation, sweating)
How is blood glucose regulated?
high blood sugar: promotes insulin release by the pancreas, stimulates glycogen formation in the liver, and glucose uptake form food which lowers blood glucose
low blood sugar: promotes glucagon release from pancreas which stimulates the breakdown of glycogen in the liver producing more glucose
What cells can be found in a cross section of the pancreas?
- islet of langerhans surrounded by acinus
- delta cells - secrete somatostatin
- alpha cells - secrete glucagon
- beta cells - secret insulin
PP cells - secrete pancreatic polypeptide
What is the blood glucose concentration?
between 4 and 8 mol/litre of blood
What is the result of hypoglycaemia?
brain function damage if sustained
What is the result of hyperglycaemia?
changes in osmolality, water retention
What else can glucose do that has negative consequences on the body?
stick to lipids and proteins which causes kidney, nerve and capillary damage
What is the relationship between insulin and glucagon?
antagonistic
What is the result of anabolic states ?
results in polymer synthesis, driven by insulin
What is the result of catabolic states?
results in polymer breakdown, driven by glucagon
What happens in the cells when blood glucose rises?
. alpha cells repressed
-> produces less glucagon
-> less glucose produced
. beta cells activated
-> produce insulin -> more glycogen made
What happens in the cells when blood glucose rises?
. alpha cells activated - produce glucagon - more glucose made
. beta cells repressed
-> reduces less insulin
-> less glycogen made
How do cells respond to insulin?
- insulin binds to receptor
- signal cascade
- exocytosis
- glut-4
- glucose entry permitted
What is the secretion of adrenaline form the adrenal gland an example of?
a neuroendocrine reflex
name hormones that are able to inhibit/ suppress anabolic reactions and stimulate/ upregulate catabolic reactions with the consequence of elevating the plasma glucose membrane
cortisol
adrenaline
glucagon
What biogenic amines are hormones?
- melatonin
- adrenaline
- thyroxine
Delta cells synthesise and secrete which hormones?
growth hormone inhibitory hormone GIHIH
Describe the sequence by which an elevation in plasma glucose conc triggers the exocytosis of insulin form pancreatic beta cells
- glucose enters cell by facilitated diffusion using GLUT2 transporter
- glucose metabolised by glucokinase to glucose-6-phosphate
- oxidation of glucose-6-phosphate to pyruvate increases intercellular ATP conc
- ATP binds to ATP dependent potassium channel causing conformational change that closes ion channel
- trapping potassium ions inside cell causes depolarisation of the plasma membrane
- depolarisation of plasma membrane opens voltage-gated calcium channels
- calcium ions flood into cell to raise intracellular calcium conc
- secretory vesicles containing insulin fuse with plasma membrane of the cell to release pre-formed insulin molecules into circulation
Definea hormone
Long distance chemical mediator secreted by an endocrine gland into the blood, which transports it to tis target cell
What is the difference between a hormone and a neurotransmitter?
- neurotransmitters are released across a neuromuscular junction or synapse -> short distance
- hormones are produced by a gland and signal via transport within the circulatory system -> long distance
What do you know about the endings of feedback loops?
negative - infinite
positive - defined end
Describe the example of oxytocin as a positive feedback loop
- initial stimulus: first contractions
- stretch sensitive neurons in cervix
- released form posterior pituitary
-> produced from hypothalamus, stored in vesicles, released from pituitary - oxytocin causes uterine muscles to contract
- after labour, stretch is lost, oxytocin production slows
- contractions stop
What is oxytocin an example of?
a neuroendocrine reflex
What is a neuroendocrine reflex?
- neurone releases hormone, not a neurotransmitter form the pituitary gland
- produced in hypothalamus, transported in vesicles along the cell body of pituitary
What triggers the adrenaline response?
neuronal signal triggers adrenaline release form vesicles in medulla of the adrenal gland which release into the blood
What do cells do in response to adrenaline?
vasoconstriction, increased heart rate, insulin suppression, amino acid, NEFAs release sensitisation of CNS
Why is the adrenaline response useful?
fight or flight
What is the relationship between melatonin and cortisol?
- pineal gland produces melatonin, adrenal gland produces cortisol
- have diurnal rhythm regulation
- balance of the regulates sleep
- no two people are the same
- shift workers insomnia - severe disruptions
- severity depends on work conduction (where)
Hyper means what?
too much
Hypo
too little
Mia means what
in the blood
What is the risk with hormone inhibitors?
overcompensation risk - patient could instantly switch rom symptoms of excess dosage to deficiency
- does must be titrated
What about taking hormones?
- hydrophobic hormone analogues active orally
- hydrophilic hormones must bypass the stomach due to stomach acid peptidase/protease enzymes
diabetes type 1
- insulin dependent diabetes
- as a result of pancreas not producing insulin
- cause only partially known
- blood glucose must be closely monitored
diabetes type 2
- blood glucose often too high
- insulin resistant diabetes
- both genetic and environmental inputs
- desensitisation of the insulin receptor
- caused by high glucose, pancreas produces more insulin, high levels of insulin, low levels of action
hyperthyroidism
- grave’s disease - thyroid attacked by immune system and produces T3 and T4 in response
- diet high in iodine
If hyperthyroidism is not a cause of an enlarged thyroid, what is the cause?
lack of iodine causes thyroid to grow
elevated TSH also causes growth
produces more thyroid hormone
Is pituitary adenoma cancerous?
no
Treating hyperthyroidism
- pharmacological inhibition of thyroid hormone synthesis
- radio-iodine
- surgery - complete or partial removal
- symptomatic treatments only
What is Cushing’s disease?
- pituitary gland benign tumours - excessive ACTH produced
- adrenal gland prices excessive cortisol
- cancerous growths of adrenal gland
How is Cushing’s disease treated?
- slow removal of steroid medication
- tumour removal
- cortisol blockers
What is Addison’s disease?
- adrenal insufficiency (primarily cortisol and aldosterone)
- destruction of the adrenal cortex (normally autoimmune, also cancerous growth or surgical removal)
- 2ndary: caused by damage to pituitary gland
- treated by steroid replacement
- hydrocortisone to replace cortisol
- DHEA supplements form health food shops
