Intro to Endocrine Flashcards
Define the endocrine system
A system that integrates + controls organ function via secretion of hormones from cells/tissues/glands which are then carried in blood to target organs, distal from site of synthesis, where they influence activity of target organ
Give an example of a fast response in the endocrine system
Increased heart rate in response to adrenaline - within seconds
Give an example of a slow response in the endocrine system
Increased protein synthesis in response to growth hormone - over days
What other chemicals should endocrine hormones not be confused with?
Paracrine
Autocrine
Exocrine
Describe the action of paracrine chemicals
Act local to site of synthesis e.g. histamine
Describe the action of autocrine chemicals
Acton on/in the same cell that synthesises the hormone e.g. cytokine
Describe the action of exocrine chemicals
Released from exocrine glands via ducts to external environment e.g. saliva, sweat, bile
What other system does the endocrine system communicate with to control all body functions?
Nervous system
How do target tissues detect endocrine hormones?
Specific receptors for the chemical are on/in cells
How do neurotransmitters travel to target sites?
Neurotransmitters released from presynaptic neurons travel across synaptic cleft to postsynaptic cell to influence its activity
Do neurotransmitters work locally or distally?
Locally within synaptic cleft
What occurs when endocrine and nervous systems combine (‘neuroendocrine’)?
Nerves release hormones which enter blood and travel to target cells
Why is response to any one hormone highly specific?
Because only target cells have receptors for the hormone e.g. adrenal medulla
While response of target cell is specific, same hormone can have different effects in diff target cells, give an example
INSULIN
In skeletal muscle/adipose tissue - increase glucose uptake
In liver - increased glycogenesis/decreased gluconeogenesis
Give examples of endocrine function embedded in a physiological system
Reproductive, renal, gastrointestinal
Endocrine system is also a diffuse system of glands in its own right - name the 4 main ones
Thyroid gland Parathyroid glands Adrenal gland Pituitary gland (and hypothalamus from nervous system)
At what concentrations do endocrine hormones exert their effects?
Very low concentrations (10-9 -10-12 M) - only need tiny amount for physiological response
How are endocrine hormones actions generally terminated?
Negative feedback loops
What are the 3 classifications of endocrine hormones?
Peptide (most common)
Amine
Steroid
What are peptide/protein hormones composed of?
Short or long chains of amino acids
What are amine hormones derived from?
One of two amino acids (tyrptophan or tyrosine) - in reality all are derived from tyrosine other than melatonin
What are steroid hormones all derived from?
Cholesterol
What are peptide hormones initially synthesised as?
Preprohormone
What does the large, inactive preprohormone contain?
One or more copies of the active hormone in their amino acid sequence
What are preprohormones cleaved into?
Prohormones (smaller, still inactive units)
Where in the cell are preprohormones cleaved?
Endoplasmic reticulum
Where are prohormones packaged into vesicles?
Golgi apparatus in endocrine cells
What are prohormones packed into vesicles alongside? And what is their function?
Proteolytic enzymes
Break down prohormone into active hormone + other fragments
What happens when release of vesicles is triggered?
All vesicle contents are released into plasma (co-secretion)
Give an example of inactive fragments being useful in clinical practice
In diabetes - C-peptide in plasma can be measured
What is a c-peptide?
Inactive fragment cleaved from insulin prohormone
What do levels of c-peptide in plasma/urine indicate?
Endogenous insulin production from the pancreas (although levels are usually about 5x higher than that of inendogenous insulin)
Why is it useful to measure C-peptide and not insulin directly?
Diabetic would be taking insulin - difficult to differentiate between that and what their pancreas is actually producing
Why do peptide hormones transport easily via the blood?
They are water soluble (lipophobic/hydrophillic)
Why is the hydrophillic property of peptide hormones a bad thing?
They cannot cross the cell membrane and so have to bind to membrane receptors on target cell
How quick are the responses once receptors are bound to peptide hormones?
Relatively fast (seconds to minutes)
How do most peptide hormones work?
Via modulating either the GPCR or tyrosine kinase linked signalling pathways
What do the GPCR or tyrosine kinase linked signalling pathways do?
Phosphorylate existing proteins in the cell and modify their function e.g. open/close ion channels, activate or inactivate enzymes
What are the 2 types of cell surface receptors peptide hormones will bind to?
G protein couple receptor
Tyrosine kinase linked receptor
Describe the mechanism of a G protein coupled receptor
Activates 2nd messenger system (which alters gene expression) and/or ion channels leading to modification of existing proteins
Does the G protein coupled receptor cause a faster or slower response?
Faster (rapid response)
Describe the mechanism of a tyrosine kinase linked receptor
Alters gene expression
Does the tyrosine kinase linked receptor produce a faster or slower response?
Slower, longer lasting activity
From which amino acid are most amine hormones derived from?
Tyrosine
What are the 3 catecholamine hormones?
Dopamine, norepinephrine, epinephrine (hydrophillic - similar mechanism of action to peptide hormones)
What are the 2 thyroid amine hormones?
Thyroxine, triiodothyronine (lipophillic - similar mechanism of action to steroid hormones)
What is the only amine hormones not derived from tyrosine and what is its function?
Melatonin, derived from tryptophan
Melatonin regulates circadian rhythm
What makes steroid hormones different to other types of hormones?
Steroid hormones are synthesised directly as needed, rather than stored and released
Why are steroid hormones synthesised directly as needed?
They are highly lipophilic so cannot be retained within lipid membranes; once synthesised they diffuse across membrane into ISF and the blood
Due to being poorly soluble in water, how are steroid hormones transported?
Bound to carrier proteins e.g. albumin
How do carrier proteins aid the transport of steroid hormones through plasma?
They stabilise transport and protect them from enzymatic degradation, phenomenally increasing their half life
What is the half life of steroid hormones compared to amine hormones?
60-90 mins for steroid; 2 mins for amine
What 4 places in the body produce steroid hormones, and what specific hormones do they produce?
GONADS - sex steroids
PLACENTA - hCG, sex steroids
KIDNEY - vitamin D3
ADRENAL CORTEX - corticosteroids
As prev said, all steroid hormones are derived from cholesterol, but how is it decided which specific hormone is ultimately produced?
Determined by diff cells having diff enzymes synthesising diff derivatives of cholesterol
Where are steroid hormone receptors located?
Inside cells (cytoplasmic or nuclear receptors)
What effect do steroid hormones have on the cell?
Either trigger activation or repression of gene function within nucleus = genomic effect (then have a knock on effect on protein synthesis)
Is the process of steroid hormone effect fast or slow?
Relatively slow process
lag time between hormone release an biological effect (hours to days) but effect persists for around the same time
Is there any unbound free steroid/thyroid hormone in plasma?
Yes, a small amount; this is the physiologically important fraction
What can be done ONLY by a free hormone?
Diffusion across capillary walls to target cells
What does the Law of Mass Action dictate?
As free hormone leaves the plasma, more hormone is released from carriers; allows for a reservoir of hormone ready for action
Free hormone + complexed hormone =
Total plasma (hormone)
What determines {Hormone}plasma ?
The balance between secretion and degradation/excretion
In most endocrine pathways, what is secretion a response to?
Negative feedback reflexes
Give an example of a hormone which operates via negative feedback reflex
Parathyroid hormone (causes increased bone resorption, increased kidney reabsorption of Ca, production of calcitrol = increased plasma Ca which triggers inhibition of parathyroid hormone)
Give a hormone which responds to a neural feedback loop
Adrenaline
Name a hormone who’s secretion is subject to multiple control mechanisms
Insulin
What affects insulin secretion?
- plasma glucose
- autonomic nerve activity
- presence of food in gut
- additional hormones such as glucagon
When normal plasma hormone concentration is disrupted, what type of responses are initiated?
Homeostatic
Prolonged exposure to low {hormone}plasma often leads to…
up-regulation of receptor number
Prolonged exposure to high {hormone]plasma often leads to…
down-regulation of receptor number
Homeostatic responses affect the hormones own receptors, but also…
receptors for other hormones (permissive or antagonistic effects)
What is a ‘permissive effect’?
Presence of one hormone enhances effect of another
Give an example of hormones working in a permissive effect
Epinephrine only modest lipolysis but with thyroid hormones greatly increased lipolysis occurs (increased synthesis of epinephrine receptors on adipocytes)
What is an ‘antagonistic effect’?
Presence of one hormone reduces the effect of another
Give an example of hormones working in an antagonistic effect
Growth hormone impairs the response to insulin by decreasing number of insulin receptors on tissues
In clinical practice, what is required to give a true picture of hormone levels?
24 hour monitoring (most hormones are released in short bursts)
