9.1 Amino Acid Hormones

Question 1

describe amino acid hormones action via cAMP secondary messenger

Answer 1

1. hormone binds, causes G_s to activate and bind to the receptor
2. GDP comes off GTP comes on
3. GTP bound G_s activates adenylate cyclase
   
   • ATP -> cAMP to activation PKA to trigger target cell response
4. PDE is used to turn off the pathway, cAMP -> 5’AMP

*can also have an inhibitory hormone that binds, activates G_i to inhibt adenylate cyclase

Question 2

what can activation of cAMP do

Answer 2

• cause action via phosphotylation (PKA)
• act via a direct effect (cAMP-GEF/Epac)

Question 3

describe amino acid action via PIP₂ mechanism

Question 4

describe amino action based hormone action with the PIP₂ mechanism

Answer 4

1. Hormone binds, G_q associates with it
2. GDP comes off and GTP comes on
3. GTP activates Phospholipase C (cleaves PIP₂ in membrane forming DAG and IP₃
4. DAG inercaats with PKC and activates it -> trigers target cell response
5. IP₃ interacts with ER and binds IP₃ receptors to release Ca²⁺
6. Calcium binds to calmodulin and then triggers response in target cell

Question 5

MOA of steriod hormones

Answer 5

*all are membrane permeable and need a carrier protein

• steriod hormone diffuses in and binds to the receptor-chaperonin complex
• receptors dissociate, then receoptor homone complex bings to hormone response elements on DNA
• will be a lag between effects because gene transcription takes some time to get going, but then will form mRNA that is sent out of the nucelous to be translated into protein

*steriord hormone will activate a bunch of gene targets

Question 6

all steriod hormones activate genes

Answer 6

FALSE

• can also have some immediate efects

Question 8

steriod hormones for treatment of breast cancer

Answer 8

• Estrogen receptor E2 involved in breast cancer
• can block binding of E2 by changing the shape of receptor complex (tamoxifen, raloxifene
• can do corepressor binding, clocks interation of 2 receptors at the gene level
• can use antiestrogens to stop receptor shuttling and cause receptor destruction

Question 9

what is herceptin

Answer 9

• HER2 (human epidermal growth factor receptor 2) positive metastatic breast cancer have a more aggressive disease
• • greater likelihood of recurrence, poorer prognosis and appoex 1/2 life expectancy o owmen with NER2 neg breast cancer
• Herceptin (Trastuzumab): antibody treatment of women with HER2 pos metastatic breast cancer
• one of few therapies and only humanized antibody with deomonstrated survivial benefit

*blcoks dimerization and targets for immune destruction