Introduction to the Endocrine System Flashcards
What is the endocrine system?
a system that integrates and controls organ function via secretion of hormones from cells, tissues or glands
What is a hormone?
- any member of a class of signalling molecule
- produced by 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
What is a neurohormone?
A hormone such as vasopressin or noradrenaline produced by nerve cells and secreted into circulation
How does the timing of response to hormones vary?
Could be
- fast (within seconds, such as heart rate increase in response to adrenaline)
- slow (over days, such as increased protein synthesis in response to growth hormone)
Endocrine hormones should not be confused with paracrine chemicals, autocrine chemicals and exocrine chemicals, what are these?
- paracrine: act local to the site of synthesis, do not travel to distant sites
- autocrine: act on/in the same cell that synthesises the hormone
- exocrine: released from exocrine glands via ducts to the external environment including the GI tract
What is an example of a paracrine chemical?
Histamine
What are examples of autocrine chemicals?
Cytokines
What are examples of exocrine chemicals?
Saliva, sweat and bile
What system does the endocrine system work with to communicate with and control all body functions?
Nervous system
What are hormones detected by at target tissues?
Specific receptors in/on the cell
No receptor means no response
How does the nervous system communicate?
release neurotransmitters from presynaptic neurons which travel across synaptic cleft to postsynaptic cell to influence activity
What does neuroendocrine mean?
- endocrine and nervous systems combined
- nerves release hormones which enter the blood and travel to their target cells
Do hormones have the same effect in every cell?
No they can have different effects in different cells, such as insulin
What effect does insulin have in the liver?
Increased glycogenesis
Decreased gluconeogenesis
What effect does insulin have in skeletal muscle/adipose tissue?
Increased glucose uptake
What is glycogenesis?
Formation of glycogen from glucose
What is gluconeogenesis?
Formation of glucose from non-carbohydrate substances
What are examples of principle endocrine glands?
- hypothalamus
- pituitary gland
- thyroid gland
- parathyroid gland
- pancreas
- adrenal glands (suprarenal)
What are some features of an endocrine hormone?
- produced by a cell/group of cells
- secreted into blood
- transported to distant targets
- act by binding to receptors on target
- exert their effect at very low concentrations (range of 109-1012)
- have their action terminated, often via negative feedback loops
Do hormones act at high or low concentrations?
Capable of acting in low concentrations (109-1012)
What are the different classifications (types) of endocrine hormones?
Peptide or protein hormones
Amine hormones
Steroid hormones
What are peptide or protein hormones composed of?
Chains of amino acids
What are amine hormones derived from?
One of two amino acids (tryptophan or tyrosine)
What are steroid hormones derived from?
Cholesterol
What is the most common classification of hormone?
Peptide hormone
What are examples of peptide hormones?
TRH
FSH
Insulin
Explain the process of forming peptide hormones?
- large and inactive preprohormone produced by ribosomes; contains one or more copies of the active hormone in their amino acid sequence
- cleaved into smaller units in endoplasmic reticulum but still inactive proteins called prohormones
- packaged into vesicles in golgi apparatus, along with proteolytic enzymes which break the prohormone down into active hormone and other fragments
- stored in vesicles in endocrine cells until release is triggered and all vesicle contents are released in plasma (co-secretion)
What are peptide hormones synthesised as?
Preprohormone which needs cleaved into prohormone and stored in vesicles until required
What is the original peptide hormone produced by?
Ribosomes
Where is preprohormone cleaved into smaller units called prohormones?
Endoplasmic reticulum
Where is prohormone packaged into vesicles?
Golgi apparatus
What is prohormone packaged into vesicles with?
Proteolytic enzymes, which break prohormone down into active hormone and other fragments
What is an example of an inactive fragment produced during the formation of peptide hormone?
C-peptide
What is C-peptide?
Inactive fragment cleaved from the insulin prohormone
What does the levels of C-peptide in plasma or urine indicate?
A measure to indicate endogenous insulin production from the pancreas
By what ratio is C-peptide present compared to insulin?
5x higher due to insulin being metabolised faster
Are peptide hormones hydrophillic or hydrophobic?
Hydrophillic (lipophobic)
Explain the mechanism of action of peptide hormones?
- water soluble so dissolves easily in plasma for transport
- cannot cross cell membrane so bind to membrane bound receptors on target cells
- once bound receptors create fast biological responses (seconds to minutes) via modulating either the GPCR or tyrosine kinase linked signalling pathways
- these pathways phosphorylate existing proteins in the cell and modify their function
What are the two signalling pathways that peptide hormones normally use?
- G protein coupled receptor (GPCR)
- tyrosine kinase linked receptor
What do the GPCR and tyrosine kinased linked signilling pathways do?
phosphorylate existing proteins in the cell and modify their function eg:
- open or close ion channels
- activate or inactivate enzymes
What happens when peptide hormones bind to G protein coupled receptor?
activate second messenger system and/or ion channels leading to modification of existing proteins
(second messengers may also alter gene expression)
What happens when peptide hormones bind to tyrosine kinased linked receptor?
Alters gene expression
Which of G protein couple receptor and tyrosine kinased linked receptor produces a faster response?
GPCR - rapid response
Tyrosine kinase - slower, longer lasting activity
Are peptide hormones vulnerable to degradation before reaching their target compared to other classes of hormones?
Yes, also have a short half life in plasma which is usually minutes so prolonged action therefore requires continued secretion
What does GPCR stand for?
G protein coupled receptor
What are the different classes of amine hormones?
Catecholamines
Thyroid hormones
What are examples of catecholamine hormones (and therefore amine hormones)?
Dopamin (CNS neurotransmitter)
Norepinephrine (neurotransmitter)
Epinephrine (hormone released by adrenal medulla)
Do catecholamines have a similar mechanism of action to peptide hormones or steroid hormones?
Peptide hormones (are hydrophillic)
Do thyroid hormones have a smiliar mechanism of action to peptide hormones or steroid hormones?
Steroid hormones (lipophillic)
What are most amine hormones derived from?
Tyrosine, only one not is melatonin which is derived from tryptophan
What is the function of melatonin?
Regulate circadian rhythm
Are steroid hormones stored or synthesised directly as needed?
Synthesised directly, unlike other hormones which are stored and then released when needed
Why are steroid hormones produced as needed and not stored?
- they are high lipophillic so cannot be retained within lipid membranes
- once synthesised they diffuse across the membrane into the ISF and then blood
How are steroid hormones transported in blood?
Bound to carrier proteins (such as albumin) due to being poorly soluble in water
What are advantages of steroid hormones binding to proteins for transport?
Stabilises their transport through plasma and protects them from enzymatic degradation
Increases half life (to 60-90 minutes from 2 minutes for amine hormones)
What are examples of organs that produce steroid hormones?
Gonads (testes and ovaries - sex steroids)
Placenta (hCG, sex steroids)
Kidney (vitamin D3)
Adrenal cortex (corticosteroids)
What is the specific steroid hormone ultimately produced determined by?
different cells having different enzymes synthesising different derivatives of cholesterol
- all steroid hormones are derived from cholesterol
Explain the mechanism of steroid hormones?
- lipophillic: cross the plasma membrane easily, both in and out of cells
- receptors are located inside cells (cytoplasmic or nuclear receptors) and trigger either activation or inhibition of gene function within the nucleus (genomic effect)
- genes control synthesis of proteins so this either increases or decreases protein synthesis
- relatively slow process so time lag between hormone release and biological effect (hours to days) but effects persist for around the same time
Are steroid hormone receptors on the cell surface or inside the cell?
Inside as they are lipophillic so can cross plasma membrane easily
Some evidence suggests there may be come surface receptors also
Is the mechanism of action of steroid hormones a slow or fast process compared to other classes?
Slow response (hours to days)
For steroid/thyroid hormone, what side is the free hormone:hormone-protein complex ratio leaning towards?
- bound (complexed) hormone
- important as only free hormone is physiologically active
Why in health does the amount of free hormone remain constant?
- Law of Mass Action dictates that as free hormone leaves plasma (taken up by cells) more hormone is released from carriers
- typically one minute quantities of hormone are required for physiological functions
What is the total plasma hormone level composed of?
Free hormone + complexed hormone
Why do steorid/thyroid hormones bind to carrier proteins?
They have poor solubility in plasma
What are the different kinds of carrier proteins that steroid/thyroid hormones can bind to?
Specific (such as corticosteroid-binding globulin)
Non-specific (such as albumin)
What are the advantages of steroid/thyroid hormones binding to carrier proteins?
Increases solubility
Protects from degradation, increasing half-life to more than 60 minutes
What is hormone concentration in the plasma determined by?
Balance between secretion and degradation/excretion
In most endocrine pathways, what is hormone secretion responsive to?
Negative feedback reflexes
Some also respond to neural feedback loops
In addition to loops, what else can the secretion of some hormones be subject to?
Multiple control mechanism, such as insulin which is subject to:
plasma [glucose]
Autonomic nerve activity
Presence of food in gut
Additional hormones such as glycogen
What is the homeostatic response to prolonged exposure to low [hormone]plasma?
up-regulation of receptor number
- increased tissue sensitivity to hormone
Conversely, prolonged exposure to high [hormone]plasma leads to down-regulation of receptor number (decreases tissue sensitivity to hormone)
What are the different ways that hormone concentration can effect receptors for other hormones?
Permissive effects
- presence of one hormone enhances the effect of another
Antagonist effect
- presence of one hormone greatly reduces the effect of another
What is an example of a hormone having a permissive effect on another hormone?
- epinephrine causes only modest lipolysis in adipose tissue
- when thyroid hormones are also present there is greatly increased lipolysis
- thyroid hormone increases number of receptors for epinephrine in adipocytes
- TH itself has no effect on lipolysis but is permissive to epinephrine
What is lipolysis?
When triglycerides are broken down (hydrolysed) into glycerol and three free fatty acids
What is an example of a hormone having an antagonistic effect on another hormone?
Growth hormone impairs response to insulin by decreasing number of insulin receptors on tissues
Should measurement of hormones in plasma, clinically, be an instantaneous measurement or average over 24 hours?
Average over 24 hours due to hormones being released in short bursts and [hormone] varying wildly
