04 Melanocyte stimulating hormone (MSH)

Alternative names for MSH?

Intermedins, melanotropins

What is biochemical classification of MSH

Peptide

Where is MSH expressed

pituitary gland, hypothalamus, skin cells

Where is MSH derived

Precursor prohormone proopiomelanocortin (POMC)

What are the three different primary sequences of MSH? (three primary forms of MSH)

a-MSH, b-MSH, y-MSH

What is the function of b-MSH?

Still being investigatedW

WHat is function of y-MSH?

Regulates metabolic functions, energy homeostasis, food intake, sodium (Na+) balance, and blood pressure regulation

Corticotropin-like intermediate peptide (CLIP)

Suggested to be an insulin secretagogue

ACTH

regulates cortisol and androgen production

b-endorphin

secreted in response to pain

B-liptropin

involved in lipolysis and steroidogenesis

y-lipotropin

involved in lipolysis and steroidogenesis

Evidence suggests that which peptides/melanocortins also have endorphin-like activitiy?

b-lipotropin, y-lipotropin (still classified as peptides)

Draw the composition of the various melanocortins on a chromosome

PAGE 2 SLIDE 3

All melanocortins are post-translational products of…

POMC protein

What are melanocortins?

Group of peptides which include adrenocorticotropic hormone (ACTH) and different forms of melanocyte-stimulating hormone (MSH), and are derived from proopiomelanocortin (POMC) in pituitary gland

What receptors do melanocortins bind to?

melanocortin receptors

High concentrations of ACTH have what kind of activity in human beings?

melanotropic activity

What is the synthesis of proopiomelanocortin (POMC)?

expressed primarily in corticotropic cells in anterior pituitary and melanotropic cells (melanotrophs) in pars intermedia

MSH is produce from the same precursor molecule as…

adrenocorticotropic hormone (ACTH), the precursor molecule is called pro-opiomelanocortin (POMC)

Where is melanocyte stimulating hormone (MSH) produced from in LOWER VERTEBRATES?

Intermediate lobe of pituitary gland

What is a result of MSH secretion in lower vertebrates?

dramatic darkening of skin of fishes, amphibians, and reptiles

What causes darkening as a result of MSH release in fishes, amphibians and reptiles?

Granules of melanin spreading through branches of specialized pigment cells (melanophores)

What is the action of MSH in humans?

MSH stimulates melanocytes to inject melanin through long processes onto keratinocytess present within rest of skin

What form of MSH is responsible for tanning of humans?

a-MSH

What layer of skin is melanocyte found in?

stratum basale/basal layer, lowest layer of epidermis just above basement layer

What layer of skin is keratinocytes found in (living ones)?

Stratum spinosum aka squamous cell layer of the epidermis, just above basal layer

What pigment is eumelanin?

Black or brown pigment

What pigment is pheomelanin?

Red or yellow

TASK: TRACE PATHWAY OF SUNLIGHT TO MELANIN RELEASE ON SLIDE 9, PG 5

do this asap

What is a result of mutations in melanocortin-1 receptor?

Red hair and fair skin; red hair due to overabundance of pheomelanin pigment relative to eumelanin

Compare stability of eumelanin and pheomelanin

Eumelanin is UV absorbent, pheomelanin is photo-unstable and possibly promote carcinogenesis

What peptide is a-MSH derived from

ACTH, derived from POMC, proopiomelanocortin

What peptide is y-MSH derived from

proopiomelanocortin

What peptide is b-MSH derived from

y-lipoprotein, derived from b-lipotropin, derived from proopiomelanocortin

DRAW DIAGRAM ON SLIDE 11, PG 6

what she said

DRAW TABLE ON PG 6 slide 12

what she said

agonist affinity of MC1R:

a-MSH >= ACTH = B-MSH > y-MSH

main function of MC1R

pigmentation

agonist affinity of MC2R:

adrenal steroidogenesis

Agonist affinity of MC3R:

y--MSH = a-MSH = ACTH > b-MSH

main function of MC3R:

energy rheostasis (regulation of energy balance, designates changes in regulated levels); involved in sexual function

agonist affinity of MC4R:

a-MSH >= ACTH > b-MSH > y-MSHm

main function of MC4R:

energy homeostasis (also involved in sexual function)

agonist affinity of MC5R:

a-MSH >= ACTH > b-MSH > y-MSH

main function of MC5R:

exocrine gland secretion

MC1R structure

Gs (stimulatory) - protein coupled receptor with seven membrane spans

how many melanocortin receptors are there

5

what is agouti signaling peptide (ASIP)

responsible for distribution of melanin in mammals and antagonist for a-MSH; binds to MC1R

what is agouti-related peptide (AgRP)

neuropeptide produced in brain by AgRP/NPY neuron; AgRP is co-expressed with NPY (neuropeptide Y); acts to increase appeptite and decrease metabolism and energy expenditure

Which ligands are considered agonists for melanocortin receptors…

a-, b-, and y-MSH and ACTH

MC1R signaling

DESCRIBE PROCESS ON SLIDE 18, PG9

MC3R and MC4R Signaling

AgRP is endogenous antagonist of melanocortin receptors MC3R and MC4R

What is melanotan

Melanocortin receptor analogues (synthetic version of a-MSH)

What is melanotan 1

injection that darkens the skin; ability to get tan without risks of exposure to UV light

What is melanotan 2

“barbie drug” - second synthetic version of MSH, also darkened skin of male volunteers; unexpectedly caused penile erections, possibility to use to treat erectile dysfunction