Introduction to Endocrinology Flashcards
Name the 3 ways hormones can be classified?
- Protein/polypeptide hormones
- Steroid hormones
- Miscellaneous-Thyriod hormones because they have iodine in their structure
What are steriod hormones derived from?
Derived from cholesterol
List the steps for hormone synthesis?
EXAMPLE: Adrenocorticotropic Hormone (ACTH)
Prohormone of ACTH: Pro-opiomelanocortin (POMC)
Also draw a diagram
- Specific mRNA sythesized within cell nucleus
- Translation of specific mRNA to prohormone,POMC, in rough ER
- Prohormone transported to Golgi apparatus where processed by proteolytic enzymes to mature, active hormone (these hormones are located within the vesicles)
- By the time the vesicle has reached the plasma memebrane, the proteolytic enzyme has activated the enzyme
- Cleavage of the pro-hormone leads to generation of the active hormone
- Vesicles filled with active hormone (e.g. ACTH) accumulate near the cell surface - when a signal arrives, you get exocytosis and the ACTH is released into the blood
Which blood vessels are pituitary hormones secreted into?
Pituitary capillary
In which cell is Cortisol produced?
adrenal cortical cell
List the steps for Hormone Synthesis?
- LDL rich in cholesterol transferred into cell by endocytosis and are stored as Fatty Acid Esters (seen as fat droplets).
- To synthesise steroid hormones you need to break down the fatty acid esters to liberate cholesterol
- Esterase enzymes break down the fatty acid esters
- The cholesterol molecule is carried into the mitachondria using the StAR protein.
STEROID HORMONES ARE MADE IN THE MITOCHONDRIA
This is one of the rate limiting steps in steroid hormone production
The more StAR proteins you have, the more cholesterol you can get into the mitochondrion and the more steroid hormone you can produce
When cholesterol enters the mitochondrion, there are lots of enzymes that allows the step-wise conversion of the cholesterol into the steroid hormone of choice
The enzymes present in certain cells determines the final steroid hormone product (e.g. adrenal cortical cells have a set of enzymes that produced cortisol
- once mature hormone produced, it can freely diffuse across the cell membrane into the circulation
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What is the role of esterase?
Breaks down fatty acids and liberates cholesterol
What does the StAR protein do?
Carries cholesterol into the mitachondria
Where are steriod hormones mostly stored?
In the blood, proteins like albumin bind to hormones. There are also specific binding globulins (i.e. CBG).
Write a question about their function
What is the DIFFERENCE BETWEEN POLYPEPTIDE HORMONE AND STEROID HORMONE SECRETION:
Protein/polypeptide hormones are stored in vesicles in the cell, awaiting a stimulus triggering exocytosis
Steroid hormones are secreted into the blood stream as soon as they are produced - they’re very lipid soluble
How are protein hormones transported in the blood ?
Protein/polypeptide hormones are secreted into the blood and travel UNBOUND to the site of action
Why do protein hormones have very short half lives?
Protein/polypeptide hormones are secreted into the blood and travel UNBOUND to the site of action
Protein/polypeptide hormones, as a result, have VERY SHORT HALF LIFES
They aren’t bound to any plasma proteins in the blood so they are sensitive to enzymatic break down
Half life is usually a matter of minutes
How are steriod hormones transported in the blood?
Talk about all the different ways it is transported in the blood.
Stored in the BLOOD
They bind to a number of plasma proteins
Albumin - present in large amount in the plasma - it can mop up a large amount of most steroid hormones but the interaction isn’t very specific
For each individual steroid hormone there tends to be a fairly specific plasma protein which forms a much stronger binding (e.g. Cortisol - Corticosteroid Binding Globulin (CBG))
The vast majority of steroid hormone will be bound to plasma proteins in the blood
There is a small amount of free steroid hormone in the blood
What is the difference between steriod hormones unbound by a plasma protein or bound to a plasma protein?
NOTE: If the steroid hormone is bound to a plasma protein then it is not leaving the blood stream - only free steroid hormone can move into the tissues
Write down the equilibrium for plasma protein, hormone and protein bound hormone
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Referring to the steriod hormone equilibrium.
What will happen if you have an uptake of steriod hormone by the tissue?
EXAMPLE: Cortisol is a stress hormone.
At times of stress, more of the free cortisol enters the tissues and the concentration of free cortisol begins to fall.
Some of the protein bound hormone releases to try and maintain the free steroid hormone levels in the blood
If the tissues start to use up more steroid hormone - it stimulates the endocrine cells to produce more of the steroid hormone
Referring to the steriod hormone equilibrium.
What will happen if you have a rise in plasma protein level?
The more plasma proteins you have, the more likely it is that the plasma proteins are going to bind to steroid hormone and so more protein bound hormone is formed.
The equilibrium is maintained.
EXAMPLE: Pregnancy - plasma proteins that bind to cortisol
Plasma proteins that bind to cortisol rise massively during pregnancy
This sends a message to the endocrine cells to increase steroid hormone synthesis
This maintains the level of free cholesterol in the blood
Anything that shifts the equilibrium will stimulate the endocrine cells to produce more steroid hormone.
What is the mechanism of action for a peptide hormone.
Use ACTH as an example
Protein/polypeptide hormones aren’t generally lipid soluble so you need a protein receptor to recognise the hormone - ACTH Receptor (in the adrenal gland)
The receptors are usually G-protein coupled receptors
Binding of ACTH to the ACTH receptor activates Adenylate Cyclase which causes an increase in cAMP production from ATP
Increase in cAMP activates Protein Kinase A
Esterase is phosphorylated which liberates cholesterol
In addition, the phosphorylation of StAR Protein activates the StAR Protein - allowing cholesterol to move into the mitochondrion
This stimulates steroid hormone production
The protein/polypeptide hormone ACTH influences the production of steroid hormone cortisol
What is the mechanism of action for a steriod hormone.
Only free steroid hormones can get into cells
They are very lipid soluble so can diffuse through the membrane
Steroid Hormones bind to INTRACELLULAR RECEPTORS
Once bound to the receptor, they translocate to the nucleus and have a massive effect on DNA Transcription and subsequent translation
Steroid hormone have a massive effect by changing the protein machinery within the cell
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What is the mechanism of action for a peptide hormone.
Use cortisol as an example
Free Cortisol enters cell by passive diffusion
Binds to specific Glucocorticoid (GC) receptors in cell cytoplasm
This hormone-receptor complex travels to nucleus & binds to specific DNA binding sites
Leads to changes in transcription rates of specific genes and production of mRNA
Translation of mRNA to protein within endoplasmic reticulum
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State the negtative feedback mechanism for cortisol.
Start of with ACTH
Anterior pituitary is stimulated by stress
Protein/polypeptide hormone ACTH is released
ACTH acts on the adrenal gland to increase cortisol production
Cortisol enters the bloodstream and carries out its function to decrease stress
Cortisol returns to the anterior pituitary and switches ACTH off (end consequence is that Cortisol production is also switched off)
