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REGUB2: Cellular Mechanisms of Hormone Action (i) (Hormone Classification,…
REGUB2: Cellular Mechanisms of Hormone Action (i)
Intro
hormones = chemicals released by cells that impact on gene expression/protein state. They complement NTs (adjacent contact, broadcast message)
Hormonal signalling can be...
autocrine (act on same cell)
paracrine (act on adjacent cells)
endocrine (act on distant cells)
Hormones are specific + potent through Rs
Factors influencing degree of response
1) delivery of hormone
synthesis/secretion rate
target proximity
dissociation constants with transport proteins
rate of conversion to active
clearance rate by liver/kidney
2) R/Tissue Status
density/ state of occupancy
Hormone Classification
1) by chemical nature
steroid hormones (eg cortisol)
protein/peptide hormones (eg PTH)
glycoprotein hormones (eg LH)
iodothyronine (eg T3+T4)
2) by R type
intracellular
cell surface
3) by secondary messengers
cAMP
cGMP
kinase
phosphatase
4) by solubility
group 1 = hydrophobic
steroids, iodothyronines, calcitriol
protein carrier bound in plasma
long T1/2
intracellular R
slow development effects
mediator = Hormone-R complex
group 2 = hydrophilic
peptides/proteins, catechols
free in plasma
short T1/2
cell surface R
rapid metabolic effects
mediator = second messenger
Signalling
Group 1
1) diffusion
2) bind to R
3) translocation
4) bind to hormone response element
5) mRNA + protein expression
Group 2
1) bind via GPCRs on membrane
2) intracellular secondary cascade (propagates + amplifies signal)
3) cAMP activates PKA
4) selective protein phosphorylation by phosphodiesterase enzymes
ensure rapid cAMP turnover
ensure rapid termination once hormone is removed
regulated by cAMP,cGMP,hormones,Ca2+
Hormone response elements
regions of DNA close to transcription start site (upstream/5')
associate with nuclear Rs as well as activated Rs
adds further complexity/control
Other secondary Rs
Ca2+
activates phospholipase C
produces IP3
Ca2+ channels open
intracellular conc decreases
cGMP
GPCR independent
driven by granulate cyclase (membrane bound R)
produces ANF
causes smooth muscle relaxation + decreases BP