Melanocortinin System Flashcards
what are the 13 components of the melanocortin system?
4 posttranslational peptide products of the proopiomelanocortin (POMC) hormone : melanocortin peptides a-, b- and g- melanocyte-stimulating hormone and adrenocorticotropic hormone (ACTH)
5 Melanocortin receptors : MC1R, MC2R, MC3R, MC4R & MC5R (these are 7-membrane G-coupled protein receptors)
2 Melancortinin antagonists : Agouti and Agouti related protein (AGRP)
2 modulators : mahogany and syndecan-3
Give examples as to how the melanocortinin system relies on tissue specificity
- a-MSH produced in brain inhibits food intake
- a-MSH in skin acts on melanocytes (which contain melanins or pigments that influence skin colour in humans and coat in rodents)
- MCR relates to adrenal; skin; brain; penis, etc
What would result from mutations in POMC gene ?
>Early onset obesity (a-MSH produced in brain inhibits food intake)
>Altered Pigmentation (a-MSH in skin acts on melanocytes)
>Sexual function/dysfunction (MCR)
Early onset obesity is a POMC mutation where ?
MCR4 mutation
How does a-MSH increase brown/black pigment in skin?
> MC1R receptor binds to a-MSH and activates signal pathways
> G protein-coupled receptors attach to AC and convert ATP into cAMP which acts on PKA and CREB
> CRE dna synthesizes MITF which leaves the nucleus
> MITF returns back into the nucleus and promotes transcription of melanogenis enzymes; Tyrosinase/DCT
How does a mutation result in yellow and obese mice ?
Agouti mice have a mutation which results in an overproduction of agouti protein
>recall; agouti protein is an antagonist to MCR1
Agouti mice overeat because agouti protein blocks MC4R in the brain
>as a result, they get/are a model for adult-onset obesity, hyperglycemia, insulin resistance
what is PT-141 ?
it is an a-MSH analogue
> erectile dysfunction treatment in the form of nasal spray; directly targets the brain instead of affecting blood vessels in the penis
PT-141 competes with a-MSH (MC3R) to bind to receptors
