1- Introduction To Endocrinology Flashcards
How are protein hormones transported
• 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
• Protein/polypeptide hormones are stored in the tissues that produce them
• 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 steroid hormones transported
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
• 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
Describe ACTH negative feedback
a. Anterior pituitary is stimulated by
stress
b. Protein/polypeptide hormone ACTH
is released
c. ACTH acts on the adrenal gland to increase cortisol production
d. Cortisol enters the bloodstream and carries out its function to decrease
stress
e. Cortisol returns to the anterior pituitary and switches ACTH off (end
consequence is that Cortisol production is also switched off)
Give an example of a protein hormone
Adrenocorticotropic Hormone (ACTH)
• Produced by the anterior pituitary
• IMPORTANT CONCEPT: these hormones are usually produced as
PROHORMONES which are cleaved to generate the hormone
• Prohormone of ACTH: Pro-opiomelanocortin (POMC)
What type of hormones come from the anterior pituitary
Protein
Describe how protein hormones are synthesised
The blood supply provides amino acids which can be used to synthesise the hormone
• Chosen pro-hormone is transcribed from the DNA and the mRNA moves into the cytoplasm and bind to the rER
• Pro-hormone is endocytosed into the Golgi apparatus
• Golgi adds enzymes to the vesicles containing the pro-hormone which cleave
the pro-hormone
• 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
Describe steroid hormone synthesis
- Cholesterol is delivered to the cell in the form of LDLs
- Cholesterol is then stored in the cell as Fatty Acid Esters and appear as fat droplets
- Steroid hormone producing cells have lots of fat droplets
- Most steroid hormones are produced by the Adrenal Glands or the Gonads
- To synthesise steroid hormones you need to break down the fatty acid esters to liberate cholesterol
- Esterase enzymes break down the fatty acid esters
- STEROID HORMONES ARE MADE IN THE MITOCHONDRIA
- Cholesterol gets into the mitochondrion via StAR Proteins (Steroidogenic Acute Regulatory Protein)
- 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)
How can the Equilibrium of plasma protein bound and unbound steroid hormone in the blood shift
Uptake of steroid hormones 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
b. Rise in plasma protein levels
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
Describe peptide hormone action mechanism using ACTH as an example
The protein/polypeptide hormone ACTH influences the production of steroid hormone cortisol
• 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
Describe steroid hormone ,mechanism of action
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
Which cell produces ACTH
pituitary corticotroph cell
Which blood vessels are pituitary hormones secreted into?
Pituitary capillary
Which cell produces cortisol
adrenal cortical cell
Which target would cortisol bind to induce negative feedback within the
anterior pituitary?
Glucocorticoid receptor- cortisol has to bind to a receptor to have an effect in tissue
Describe ACTH/ cortisol negative feedback
Anterior pituitary is stimulated by
stress
b. Protein/polypeptide hormone ACTH
is released
c. ACTH acts on the adrenal gland to increase cortisol production
d. Cortisol enters the bloodstream and carries out its function to decrease
stress
e. Cortisol returns to the anterior pituitary and switches ACTH off (end
consequence is that Cortisol production is also switched off)
