Introduction to Endocrinology Flashcards
What are the three groups of hormone?
Protein/peptide
Steroid
Miscellaneous
What are peptide hormones initially produced as? Give an example.
Inactive prohormones
E.g. ACTH is produced as pro-opiomelanocortin (POMC)
Describe the synthesis of protein/peptide hormones.
Amino acids are delivered to the cell. These are used to synthesise the peptide hormones in the same way that all proteins are synthesised. Genome –> mRNA –> protein
What are all steroid hormones derived from?
Cholesterol
How is cholesterol stored in cells and what do they look like in the cell?
Cholesterol is delivered in LDLs and then it is stored as fatty acid esters, which appear as fatty droplets in the cell. Steroid producing cells have a lot of fat droplets.
Where are most steroid hormones produced?
Adrenals and gonads
What enzyme breaks down fatty acid esters?
Esterase
Where does steroid hormone synthesis take place within the cell?
Mitochondrion
How does cholesterol get into the mitochondrion?
Via StAR proteins (steroidogenic acute regulatory proteins)
As all steroid hormones are derived from cholesterol, what determines the final hormone produced?
The combination of enzymes that are found within the cell
State some key features of protein/polypeptide hormones and state how they are stored.
Protein/polypeptide hormones are stored in the cells that produce them. They have a short half life.
How are steroid hormones transported/stored?
They are transported in the blood - bound to carrier/plamsa proteins such as albumin or other specific carriers such as cortisol and corticosteroid binding globulin(CBG).
State two ways in which the steroid hormone equilibrium in the blood can be shifted.
- Uptake of steroid hormones by tissue - leads to the release of some of the protein bound hormone to re-establish previous free steroid hormone levels.
- Rise in plasma protein levels - more plasma proteins means that you are more likely that the plasma proteins will bind to the hormone so more protein bound hormone is formed.
Give two examples of how the steroid hormone equilibrium can be shifted.
Cortisol is a stress hormone and in times of stress, more of the free cortisol enters the tissues so the free cortisol levels fall. Some of protein bind hormone release cortisol to maintain free steroid hormone blood levels.
In pregnancy more plasma proteins are synthesised.
Describe the mechanism of action of ACTH in stimulating cortisol production.
- ACTH receptors are usually G-protein coupled receptors.
- Binding of ACTH to the receptor activates adenylate cyclase, which converts ATP to cAMP. The increase in cAMP activates Protein Kinase A.
- Esterase is phosphorylated, and so cholesterol is liberated.
- Phosphorylation of the StAR protein activates the StAR protein allowing cholesterol to move into the mitochondrion. This then stimulates steroid hormone production.
What type of receptor do steroid hormones bind to and what is their mode of action on target cells
Intracellular receptors - they act as transcription factors
once bound to receptor they translocate to the nucleus and effect DNA transcription and subsequent translation
They change protein machinery of cell.
Describe the feedback loop of ACTH and cortisol.
- The anterior pituitary is stimulated by stress and ACTH is released.
- ACTH acts on the adrenal gland to increase cortisol production. Cortisol reduces stress ( its function)
- Cortisol returns to the anterior pituitary and switches off cortisol production.
NEGATIVE FEEDBACK
What’s the pro-hormone for ACTH?
Pro-opiomelanocortin ( POMC)
How long do peptide hormones last in blood and why?
A few minutes - they have a quick discrete action
Peptide hormones are broken down quickly via enzymatic action
Which blood vessels are pituitary hormones secreted into?
pituitary capillary
Provide an example of a peptide and steroid hormone
ACTH = peptide Cortisol = steroid
What happens in terms of CBG during pregnancy?
Pregnancy increases CBG levels –> cortisol levels rise to ensure a constant level of free hormone available to tissues
What’s the main rate limiting step for steroid hormone synthesis?
Transporting cholesterol into the mitochondria
What determines the final steroid hormone product?
The enzymes present in certain cells determines the final steroid hormone product eg adrenal cortisol cells have enzymes to produce cortisol.
