USMLE Step 1 - Endocrine: peptide hormones

Hello all fellow students,  

I will be posting some study material for USMLE Step 1 that I am preparing for myself.  I find them helpful.  I am starting with Endocrine: peptide hormones.  I hope you will find them helpful.  If you want any specific topics to be posted, please let me know.  I will see if I have notes for them.   

Hormones

Three types of classification

1)      Control – is it controlled by brain or not

2)      Receptors

a.       Tyrosine Kinase linked

b.      Intracellular receptors

c.       Others

3)      Chemical composition

a.       Peptide/protein

b.      Steroid – derived from cholesterol

c.       Amine hormones – derived from

                                                               i.      Tyrosine or

                                                             ii.      Tryptophan

Properties Peptide Hormones

1)      Made in advance

2)      Stored in secretory vesicles

3)      Released by exocytosis

4)      Transport in blood by dissolved in plasma

5)      Short half life

6)      Activation of second messenger systems

7)      Modification of existing proteins + induction of new protein sysnthesis

8)      Examples: insulin, parathyroid

9)      Water soluble

10)   No carrier protein is need for transport EXCEPT:  IGF (lipid soluble – need a protein carrier)

Peptide Hormone Synthesis, Storage, and Release

1)      mRNA binds to ribosome and links amino acids into a peptide chain èpreprohormone (which is directed to RER by a signalling sequence).

2)      Prohormone is produced in RER by è an enzyme cleaving the signalling sequence.

3)      Prohormone passes from RER to Golgi

4)      Secretory vesicle è enzymes + prohormone bud off Golgi

a.       In the secretory vesicle prohormone is cleaved è active peptide + peptide fragments

5)      Secretory vesicles releases the fragments into the ECF by excocytosis (Calcium dependent)

6)      Hormone is in circulation; heading for the target organ. 

·         Secretory vesicles containing peptides are stored in the cytoplasm of the endocrine cell until the cell receives a signal for secretion. 

Post Translational Modification of Prohormones

1)      Examples:

a.       Prohormone – TRH (thyrotropin releasing hormone) contains multiple copies of the hormone

b.      Pro-opiomelanocortin:  prohormone splits into 3 active peptides + 1 inactive fragment.

c.       Proinsulin = insulin + c peptide (clinical correlate:  measuring the levels of the C peptide in the blood of diabetics to monitor how much insulin the pancreas is producing). 

Cellular Mechanism of action of peptide hormones

Peptide hormones are:

1)      Lipophobic

2)      Unable to enter target cell

3)      Binds to surface receptor complex – initiates the cellular response by means of signal transduction system

4)      Response of cells t peptide hormones is rapid because of the second messenger system

5)      Changes triggered by peptide hormones include opening or closing membrane channels and modulating metabolic enzymes or transport proteins

6)      Some peptide hormones also have long lasting effects when the second messenger systems activate gene synthesis producing new proteins.