Introduction to Endocrine Flashcards
Give an example of a fast response caused by the endocrine system
Increased heart rate in response to adrenaline
The response may be slow (over a few days) such as increased protein synthesis as a response to growth hormone
What is the definition of paracrine chemicals, autocrine chemicals and exocrine chemicals
ALL ARE NOT TO BE CONFUSED WITH THE ENDOCRINE SYSTEM
Pararine - act local to the site of synthesis, do not travel to distant sites e.g. histamine
Autocrine chemicals - act on / in the same cell that synthesises the hormone e.g. cytokines
Exorine - released from the exocrine glands via ducts to the external environment including the GI tract (saliva, sweat, bile)
No receptor for endocrine hormone?
No response
What does the endocrine system cooperate intimately with?
Cooperates intimately with the nervous system to provide further control, particularly for long term phenomena such as growth
Where does a neurotransmitter act?
In the synaptic cleft
Give an example of where neurones produce a hormone that enters the blood?
hypothalamic – posterior pituitary axis.
Although hormones are highly specific how can a hormone exhibit different properties in different portions of the body?
Hormones can have different effects in different target cells
What is the fucntion of hormones?
To bring about an increase or a decrease in a particular activity in the target cells and tissues
What hormones does the thyroid produce?
Thyroxin and triiodothyronine (target tissue is many organs, responsible for metabolism, growth and development)
Calcitonin, primary target is in bone, meant to regulate plasma calcium levels, however the effects are minimal in humans
What hormone does the parathyroid produce?
Parathyroid hormone
Site of action - bones and the kidney
Regulates plasma calcium and phosphate levels
What hormones are produced by the adrenal cortex?
Aldosterone - Kidney is the primary target - responsible for sodium and potassium homeostasis
Cortisol - primary target is many tissues - main effect is the stress response
Androgens - primary target is many tissues - main effect is sex drive in females
What hormones are produced by the adrenal medulla?
Epinephrine
Norepinephrine
Target cell is many tissues
Main effect is the fight or flight response
What hormones are produced by the kidney?
1,25 Dihydroxy vitamin D3 - (target cell is the intestine, increases calcium absorption)
Erythropoetin (target tissue is the bone marrow - red blood cell production)
What are the concentrations of endocrine hormones?
Very low concentrations (10 to the power of minus 9/12 Moles)
What are the three classifications of endocrine hormones?
Peptide - chains of amino acids
Steroid - derived from cholesterol
Amine hormones - tryptophan or tyrosine
When is the peptide hormone synthesised?
In advance of when it is needed - it is then stored in vesicles until it is required
What is a prehormone?
It is an inactive initial protein produced by the ribosome which contains one or more copies of the active hormone in their amino acid sequence
How are prehormones converted into prohormones?
Prehormones - Cleaved into smaller units in the RER to leave smaller but still inactive proteins
What happens to prohormones?
They are packaged into vesicles in the golgi apparatus, along with proteolytic enzymes which break the prohormone down into active hormone and other fragments
What is meant by co-secretion?
When release of the vesicle is triggered, the hormone and other fragments are expelled
Give examples of peptide hormones
Thyrotropin releasing hormone
Follicle stimulating hormone
In summary - the Prehormone is made by ribosomes and is cleaved to form the prohormone in the RER. The prohormone is packaged in a vesicle with proteolytic enzymes in the golgi apparatus. Exocytosis follows (co-secretion)
What is C-peptide?
C-peptide is the inactive fragment cleaved from the insulin prohormone. Levels of C-peptide in plasma or urine are often measured to indicate endogenous insulin production from the pancreas (produced in equal amounts). However, because insulin is metabolised faster, levels of C-peptide are typically about 5x higher than endogenous insulin.
C-peptide levels are a direct measure of endogenous insulin - insulin medication for those who are diabetic will not contain these C-peptides
How are peptide hormones transported in the blood and how do they enter a cell?
Transported in the plasma because they are water soluble
Cannot cross cell membrane so bind to membrane bound receptors on target cell.
What is the response time for peptide hormone receptors?
Create relatively fast biological responses (seconds to minutes)
What pathways are often involved in peptide hormone receptors?
G protein coupled receptor or tyrosine kinase linked signalling pathways. These pathways phosphorylate existing proteins in the cells and modify their function e.g. open or close ion channels, activate or inactivate enzymes
How does a GPCR result in modification of existing proteins?
By activation of a 2nd messenger system and/or ion channels
How fast is the GPCR response?
Rapid
What is the intracellular effect of tyrosine kinase inhibitors?
Alter gene expression
Slower but longer lasting activity
Are steroid hormones stored?
No, they are synthesized directly as needed
They are lipophilic so cannot be retained within the lipid membranes, once they are synthesized they diffuse across the membrane into the ISF and the blood
How are steroid hormones transported in the blood?
They are bound to carrier proteins such as albumin - this stabilizes their transport through the plasma and protects them from enzymatic degradation, increases their half life (60-90 minutes vs 2 minutes for amine hormones)
What are steroid hormones produced by?
- Gonads (testes and ovary) – sex steroids
- Placenta - hCG, sex steroids
- Kidney - Vitamin D3
- Adrenal cortex - corticosteriods
What determines which specific steroid hormone is produced?
Different cells produce different enzymes which synthesise different derivatives of cholesterol
Where are the receptors for steroid hormones?
Located inside cells (cytoplasmic or nuclear receptors) trigger either activation or repression of gene function within the nucleus
Known as the genomic effect
What is the effect of genes being the receptors for steroid hormones?
Either increase or decrease protein synthesis
What is the time delay between a steroid hormone being released and the 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. Some evidences suggests steroids may occasionally bind to cell surface receptors → rapid response.
In summary
Steroid hormone is bound to carrier protein
Must be unbound to enter the cell
Receptor is within the cytoplasm or nucleus
Receptor-hormone complex activates or inhibits one or more gene
Corresponding mRNA transcription takes place
Translation results in new proteins
What are most amine hormones derivatives of?
Tyrosine
Only amine hormone not derived from tyrosine is melatonin which is derived from tryptophan. Melatonin regulates circadian rhythm.
Which amine hormones are said to act in a similar mechanism to peptide hormones?
Catecholamines
(Dopamine, norepinephrine, epinephrine)
What amine hormones are said to be of a similar mechanism of action to steroid hormones?
Thyroid hormones:
Thyroxine
Triiodothyronine
Describe the ratio between the free hormone : hormone-protein complex
Ratio is much in the favour of bound (complexed) hormone
What is significant about the levels of free hormone in health?
They remain constant
The Law of Mass Action dictates that as free hormone leaves the plasma (taken up by cells) more hormone is released from the carriers. Typically only minute quantities of hormone are required for physiological functions.
Free hormone + complexed hormone = Total plasma [hormone]
What two benefits are conferred by the hormone carrier protein?
Increases solubility
Protects form degradation
Why do peptide and catecholamine hormones have a short half life?
Vulnerable to degradation before they reach their target organ
There is short action so requires continues secretion
How long does the effect of a steroid hormone / thyroid hormone last?
Usually hours to days
What determines the concentration of hormone in the blood?
The rate of secretion and the rate of removal
How is removal of hormones achieved?
Excretion
Metabollic transformation
Mainly occurs in the liver and kidneys
Which hormones are secreted easily?
Catecholamine and peptide hormones
Steroids and thyroid hormones take hours and days to excrete or metabolise, because protein-bound.
What are the control mechanisms of hormone secretion?
Negative feedback such as parathyroid hormone (increase in plasma calcium inhibits the parathyroid cell)
Neural feedback (fight or flight response)
Plasma molecules
Autonomic nerve activity
Food in the gut
Other hormones
Give an example of a neural feedback loop
Adrenaline
Sympathetic discharge results in release of adrenaline from the adrenal medulla to the blood stream
When would we see an increase in the number of hormone receptors on target tissues?
After prolonged exposure to low hormone concentrations in the plasma
This increases the tissue sensitivity to the hormone
Conversely, often after prolonged exposure to high [hormone] plasma we see down-regulation = decrease in receptor number on target tissues (decreases tissue sensitivity to hormone).
May affect not only the hormone’s own receptors but also receptors for other hormones (permissive or antagonistic effects).
Give an example of a permissive effect of a hormone
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.
TH increases synthesis of receptors for epinephrine on adipocytes. TH itself has no effect on lipolysis but is permissive to epinephrine.
Why must 24 hour monitoring may be required to give the true picture of hormone levels?
Most hormones are released in short bursts so [hormone] varies widely. Clinical relevance is that single values of [hormone] may be misleading
