Cellular Mechanisms of Hormone Action Flashcards
what are two key features of hormones ?
- produced by the body
- lead to a change in cell state
what do hormones complement?
neurotransmitters = adjacent cell contact
where as hormones are broadcasters of message
When a hormone acts on a distant cell, it is called what?
endocrine
when a hormone acts on an adjacent cell, it is called what?
paracrine
when a hormone acts on the same cell , it is called what?
autocrine
the endocrine system refers to what?
refers to glands that secrete hormones
ex) the pineal gland, hypothalamus, pituitary, thyroid, skin, parathyroids etc
is hormone concentration lower or higher than concentration of lipids/sugars?
concentrations of hormones are significantly lower than concentration of amino acids, sugars, or lipids
the specificity of hormone action is driven through what?
driven through receptors - different cells express different receptors
what factors influence the degree of a response?
- Delivery of hormone
- rate of synthesis
- proximity of target cell to hormone source
- dissociation constants with transport proteins
- rate of conversion from inactive to active forms
- rate of clearance by liver/kidney
- Receptor/tissue status
- density and state of occupancy of receptors
why do some hormones bind intracellularly vs on the cell surface?
it all depends on whether the hormone can pass through the lipid bilayer
what is the classification of hormones dependent on?
dependent on solubility (lipophilic vs. hydrophilic) and receptor location
what is the mediator of a group 1 hormone vs. a group 2?
group 1= hormone receptor complex - changes gene expression= slow
group 2= uses a 2nd messenger like cAMP to alter preexisting protein structures/activity = rapid
group 1 hormones lead to…?
leads to a change in cell state which drives changes in mRNA and resulting protein expression -
-
what are the steps in group1 hormone signalling?
- diffusion- hormone diffuses across membrane
- binding - encounters specific receptors within cell
- translocation - activated receptor translocates to the nucleus
- HREs- once in nucleus, activated receptor binds to hormone response elements
- change of expression - this binding drives changes in mRNA and resulting protein expression
What are Hormone response elements?
regions of DNA - contain a sequence which associate with activated receptor and nuclear receptor proteins which control the production of proteins
*each hormone induces it’s own type of hormone response element*
hormone response elements are associated with which group of hormone?
group 1 hormones which regulate transcription of proteins
What are the steps in group 2 hormone signallig?
- binding - encounters specific receptors on cell membrane - typically G protein coupled receptors which carry signal across membrane
- intracellular signalling - activated receptor drives secondary signalling cascade which propagates the signal throught the cell
- activation of PKA - cAMP targets and activates protein kinase A
- phosphorylation - selective phosphorylation of cellular proteins - like metabolic enzymes, nuclear transcription factors
protein kinase A is a very potent…
phosphorylator
which response is more potent - group 1 or group 2?
group 2 b/c the cascade elicits a much larger response per hormone molecule
what is the role of phosphodiesterase?
it helps ensure rapid turnover of cAMP = rapid termination once hormone removed
they are regulated/influenced by cAMP, cGMP,hormones and calcium
is insulin a g protein coupled receptor?
no
what is type two diabetes (mellitus)?
insulin resistance from a decrease in insulin receptor and problems with downstream signalling
what cause of diabetes insipidus?
lots of urine - too dilute, lack of response to vasopressin, mutation in AVPR2 (vasopressin receptor)
what is Grave’s Disease?
autoantibodies to TSH receptor leads to increase in thyroid hormone production and hyperthyroidism
describe how ELISA can be used to quantify hormone levels
what are the steps of ELISA?
- coat well of plate with EPO antibody
- mix in equal volumes “test” serum with an enzyme labled “control” (which is an EPO sample of known concentration”
- add a substrate that flouresces on reaction with the enzyme
- add this mix to the reaction/assay plate and wash away unbound mix
- quantify the amount of signal emitted
*there is an inverse relationship between the amount of flourescemce and the concentration of the substrate bound*
