Introduction to the Endocrine System Flashcards
Define the endocrine system
A system that integrates and controls organ function via the secretion of chemicals (hormones) from cells, tissues or glands which are then carried in the blood to target organs, distal from the site of hormone synthesis, where they influence the activity of that target organ.
How can response times within the endocrine system vary?
- fast (within seconds) e.g. increased heart rate in response to adrenalin
- slow (over days) e.g. increased protein synthesis in response to growth hormone
What should endocrine hormones not be confused with?
- Paracrine
- Autocrine
- Exocrine
What are paracrine chemicals?
Act local to the site of synthesis, do not travel to distant sites e.g. histamine
What are autocrine chemicals?
Act on/in the same cell that synthesises the hormone e.g. cytokines
What are exocrine chemicals?
Released from exocrine glands via ducts to the external environment including the GI tract e.g. saliva, sweat, bile
What 2 systems communicate and control all body functions?
- Endocrine system
- Nervous system
How do hormones travel in endocrine communication?
Hormones travel in the blood to their target organs/tissues
How do tissues detect hormones in the endocrine system?
through the presence of specific receptors for that chemical on/in the cells
Describe neural communication.
Neurotransmitters released from presynaptic neurons travel across the synaptic cleft to the postsynaptic cell to influence its activity
What are neurotransmitters?
Neurotransmitter is the chemical released by the neuron but, in contrast to hormones, acts locally within the synaptic cleft
How is further control achieved within neural communication?
The endocrine and nervous systems co-operate intimately to provide further control, particularly for long-term phenomena, e.g. growth.
Describe neuroendocrine communication.
Endocrine and nervous systems combine
Nerves release hormones which enter blood and travel to their target cells
e.g. hypothalamic – posterior pituitary axis
Why is the response to any one hormone highly specific?
Although all hormones circulate throughout the body in the blood, the response to any one hormone is highly specific because only target cells have receptors for the hormone.
What effect does insulin have on skeletal muscle/adipose tissue?
Increase glucose uptake
What effect does insulin have on the liver?
- Increased glycogenesis
- Decreased gluconeogenesis
What is the function of hormones and neurotransmitters?
change activity of their target cells and tissues
- increase or decrease a particular activity
What are the sites of principal endocrine glands?
- Hypothalamus
- Pituitary
- Thyroid
- Parathyroid
- Adrenal glands
- Gonads
What are the 6 features of an endocrine hormone?
- Produced by a cell or group of cells
- Secreted from those cells into the blood
- Transported via the blood to distant targets
- Exert their effects at very low concentrations (act in the range 10-9 -10-12 M)
- Act by binding to receptors on target tissues
- Have their action terminated, often via negative feedback loops.
What are the classifications of endocrine hormones?
- Peptide (or protein) hormones
- Steroid hormones
- Amine hormones
What are peptide/protein hormones composed of?
Chains of amino acids
What are steroid hormones derived from?
Cholesterol
What are amine hormones derived from?
One of two amino acids (tryptophan or tyrosine)
What happens once a peptide hormone is synthesised?
Synthesised in advance of need then stored in vesicles until required
Give 3 examples of peptide hormones.
- TRH (thyrotropin releasing hormone)
- FSH (follicle stimulating hormone)
- Insulin
In peptide hormone synthesis, what do the ribosomes produce?
Preprohormones (large and inactive proteins)
What doe preprohormones contain?
one or more copies of active hormone in their amino acid sequence
What happen to preprohormones in peptide hormone synthesis?
Preprohormones are cleaved into smaller units in the RER to leave smaller but still inactive proteins called prohormones
What happen to prohormones in protein hormone synthesis?
packaged into vesicles in the golgi apparatus
with proteolytic enzymes which break the prohormone down into active hormone and other fragments
Where are hormones and other fragments stored in peptide hormone synthesis?
in vesicles in endocrine cells until release is triggered into plasma (co-secretion)
Give an example of a clinical use for measuring inactive fragments in plasma?
C-peptide in diabetes
What is C-peptide?
C-peptide is the inactive fragment cleaved from the insulin prohormone.
Why are levels of C-peptide in the plasma or urine often measured in diabetes?
indicate endogenous insulin production from the pancreas (produced in equal amounts)
Why can peptide hormones be transported via the blood easily?
Water soluble so dissolve easily in plasma making transport via the blood simple and easy
Why do peptide hormones have to bind to membrane bound receptors to cross the cell membrane?
Water solubility means cannot cross cell membrane so bind to membrane bound receptors on target cell.
How do most peptide hormones work?
- once bound these receptors generally create relatively fast biological responses (secs-mins).
- modulate either GPCR or tyrosine kinase linked signalling pathways
- these pathways phosphorylate existing proteins in the cell and modify their function
Give examples of actions that peptide hormones may have on a cell.
- Open or close ion channels
- Activate or inactivate enzymes
Which 2 kinds of cell surface receptor do peptide hormones bind to?
- G Protein Couple Receptor
- Tyrosine Kinase Linked Receptor
What happens when a peptide hormone binds to a G protein couple receptor?
Activates 2nd messenger system (may alter gene expression) and/or ion channels leading to modification of existing proteins. Rapid response
What happens when a peptide hormone binds to a tyrosine kinase linked receptor?
Alters gene expression. Slower, longer lasting activity
How do steroid hormones differ in their synthesis to other hormones?
Unlike the other types of hormones, steroid hormones are synthesized directly as needed, rather than being stored and released.
Why are steroid hormones synthesised on demand?
This is because they are highly lipophilic (lipid soluble) so cannot be retained within lipid membranes. Once synthesized they diffuse across the membrane into the ISF and the blood.
How are steroid hormones transported?
Being poorly soluble in water they are transported bound to carrier proteins such as albumin.
How is the half life of steroid hormones increased?
They are protected from enzymatic degradation as they are stabilised via binding to carrier proteins which increases their half life
What are steroid hormones produced by?
- Gonads
- Placenta
- Kidney
- Adrenal cortex
What steroid hormones do the gonads produced?
Sex steroids
What steroid hormones does the placenta produce?
- hCG
- Sex steroids
What steroid hormones do the kidneys produce?
Vitamin D3
What steroid hormones do the adrenal cortex produce?
Corticosteroids
What determines which specific steroid hormone is produced?
Which specific steroid hormone is ultimately produced is determined by different cells having different enzymes synthesising different derivatives of cholesterol
Why are the steroid hormone receptors located on the inside of cells?
Because steroid hormones are lipophilic they cross the plasma membrane easily, both into and out of cells. As such their receptors are located inside cells (cytoplasmic or nuclear receptors
What do steroid hormone receptors trigger?
Either activation or repression (inhibition) of gene function within the nucleus = genomic effect.
What is the effect of the altered gene function produced by steroid hormones?
Genes control the synthesis of protein so these hormones either increase or decrease protein synthesis.
Why is there a lag time between hormone release and biological effect?
This is a relatively slow process so there is a lag time between hormone release and biological effect (hours to days) but effect persists for around the same time
When does some evidence suggest there would be a rapid response to steroid hormones?
Some evidences suggests steroids may occasionally bind to cell surface receptors → rapid response.
What is the only amine hormone not derived from tyrosine?
Melatonin
What does melatonin do?
Regulates circadian rhythm
Give 2 examples of types of amine hormones?
- Catecholamines
- Thyroid hormones
Give 3 examples of catecholamines and where they are produced.
- Dopamine from the brain
- Norepinephrine from neurons
- Epinephrine from the adrenal medulla
What physiologically important fraction of hormone can diffuse across capillary walls?
unbound free steroid/thyroid hormone can diffuse across capillary walls to target cells
What does the free hormone: hormone (protein complex) ration favour?
bound (complexed) hormone
What does the Law of Mass Action dictate?
as free hormone leaves the plasma (taken up by cells) more hormone is released from the carriers.
- only minute quantities of hormone are required for physiological functions
What makes up the total plasma [hormone]?
Free hormone + complexed hormone
Give an example of a specific carrier protein.
Corticosteroid-binding globulin
Give an example of a non-specific carrier protein
Albumin
What are the advantages of transport via carrier protein?
- Increases solubility -> required for blood-mediated transport
- Protects from degradation -> increased half life (> 60 min)
How is the bound: unbound ratio of hormone maintained?
- As steroid taken up; more is released from carrier
- Allows for a reservoir of hormone ready for action
- Prolonged activity
Describe peptide and catecholamine hormones.
- water soluble: transported in solution in plasma
- vulnerable to degradation before they reach their target
- short half-life in the plasma, prolonged action therefore requires continued secretion.
Describe Steroid and thyroid hormones.
- lipophilic: diffuse across cell membrane into blood
- Circulate in plasma bound to specific transport plasma proteins
(eg thryoxine-binding globulin, or albumin)
so have longer half-life, usually hours to days - Alter protein synthesis via modifying gene expression
so effect also persists for hours to days.
What does the [hormone] in blood depend on?
Rate of excretion and rate of removal
How are hormones removed form the body?
excretion or metabolic transformation
mainly occurs in the liver and kidneys
Why do catecholamines and peptide hormones have a short half-life?
excreted easily so have a short half-life in plasma, minutes to hours
Why do steroid and thyroid hormone take so long to remove from the body?
take hours and days to excrete or metabolise, because protein-bound
What will most endocrine pathways respond to?
Negative feedback reflexes
What do some endocrine pathways respond to?
Neural feedback loops
What mechanisms of control is insulin subject to?
- Plasma [glucose]
- Autonomic nerve activity
- Presence of food in the gut
- Plus additional hormones such as glucagon all influence [insulin]plasma
How can hormones influence the ability of target cells to respond?
- by regulation of number of hormone receptors
- may affect not only the hormone’s own receptors but also receptors for other hormones (permissive or antagonistic)
Describe up regulation
Often after prolonged exposure to low [hormone]plasma we see up-regulation + decrease in number of hormone receptors on target tissues (increases tissue sensitivity to hormone).
Describe down regulation.
Conversely, often after prolonged exposure to high [hormone]plasma we see down-regulation = increase in receptor number on target tissues (decreases tissue sensitivity to hormone).
Permissive effects
The presence of one hormone enhances the effect of another eg epinephrine causes only modest lipolysis in adipose tissue, but when thyroid hormones are also present, greatly increased lipolysis occurs.
Why is TH permissive to epinephrine?
TH increases synthesis of receptors for epinephrine on adipocytes. TH itself has no effect on lipolysis but is permissive to epinephrine.
What is the clinical relevance of hormones being released in short bursts?
Single values of [hormone] may be misleading. 24 hour monitoring may be required to give the true picture of hormone levels