64 - Mechanism of Hormone Action & Second Messengers

1. Hormone concentration

2. Receptor number

3. Affinity of hormone for receptor

4. Duration of exposure to hormone

5. Intracellular factors - enzymes, cofactors

The final outcome of interaction of hormone and target cells depends on what 5 factors?

minimal concentration of hormone needed to elicit measurable response

What is the definition of a threshold response, in association with hormones?

dose-response relationship/curve

Hormone action/responsiveness is expressed in what way?

hormone concentration

What is the magnitude of hormone action/response correlated to?

maximum response

What kind of response is associated with a further increase in hormones not eliciting more response?

1. decrease in # target cells or total receptors/cell

2. concentration of enzymes activated by hormone

Decreases in hormone responsiveness can be caused by/based on what 2 things?

concentration of hormone producing 50% of maximal response

What is the definition of "sensitivity" in association with the hormone dose-response curve?

1. changing number of receptors

2. affinity of receptors

What are the 2 ways that sensitivity (hormone dose-response curve) can be changed?

down-regulate them

How does decreasing sensitivity via hormone receptors affect receptors?

number of affinity of receptors decreases

How are receptors affected when hormone concentrations are high?

T3

What down regulates TRH receptors in the anterior pituitary?

increasing it

Upregulating receptors affects sensitivity via hormone receptors by doing what?

sensitivity increases & there is up-regulation of receptors

With an increase in the number or affinity of receptors, how are receptors and sensitivity affected?

1. skeletal muscle

2. liver

GH is responsible for increasing its receptors in what 2 areas?

1. Hormone is recognized and binds to a membrane receptor→ hormone-receptor complex

2. Hormone-receptor complex EITHER coupled to a signal-generating mechanism OR must tact as one itself

3. Generated signal (second messenger) affects intracellular process by altering activity OR concentration of functional or structural proteins

What is the general mechanism for hormone action?

1. on cell membrane

2. within the cell

Where are hormone receptor systems found (2)?

classic cell membrane receptor systems

What receptor system(s) are the following characteristics associated with?

-Classified according to membrane receptor structure OR second messenger system used

-Usually a rapid response (minutes)

catalytic cell membrane receptor systems

What receptor system(s) are the following characteristics associated with?

-Doesn't use second messenger system, but rather an enzyme system such as kinases

-Usually a rapid response (minutes)

intracellular receptor systems

What receptor system(s) are the following characteristics associated with?

-Uses cytoplasmic or nuclear receptors

-Usually a slow response (hours)

G-proteins

What are the coupling molecules used in almost all membrane receptor systems?

G-proteins

Heterotrimeric proteins are what kind of proteins?

when GTP is bound

When are G proteins active?

when GDP is bound

When are G proteins inactive?

both

Are G-proteins stimulatory or inhibitory, or can they be both?

1. adenylyl cyclase

2. phospholipase C

3. cAMP

4. P3/Ca2+/DAG

What are the 4 second messenger systems that G-proteins can be linked to?

enzymes

What are adenylyl cyclase and phospholipase C?

second messengers

What are cAMP and P3/Ca2+/DAG?

1. Hormone binds receptor coupled by a G protein

2. GTP binds G protein and activates adenylyl cyclase

3. cAMP produced and activates protein kinase A

4. Intracellular proteins phosphorylated by protein kinase A, causing physiologic actions

5. Phosphodiesterase degrades cAMP, shutting down system

What are the events of the adenylyl cyclase system?

protein kinase A

What does cAMP activate?

protein kinase A

Intracellular proteins are phosphorylated by what?

phosphodiesterase

What degrades cAMP?

adenylyl cyclase system

The following hormones are ones that are associated with what system?

-CRH/ACTH (corticotropin-releasing hormone/adrenocorticotropichormone)

-FSH

-LH (follicle-stimulating hormone, luteinizing hormone)

-TSH (thyroid-stimulating hormone)

-ADH (antidiuretic hormone)

-Calcitonin

-PTH (parathyroid hormone)

-Glucagon

yes

Can hormones associated with the adenylyl cyclase system use multiple receptor systems?

1. Hormone binds receptor coupled by a G protein

2. GTP binds G protein and activates phospholipase C

3. Phospholipase C liberates diacylglycerol (DAG) and IP3 from PIP2

4. IP3 causes Ca2+ release from ER or SR stores

5. Ca2+ and DAG activate protein kinase C, which phosphorylates proteins

What are the events of the phospholipase C system?

phospholipase C

What liberates diacylglycerol (DAG) and IP3 from PIP2 in the phospholipase C system?

IP3

What causes Ca2+ release in the phospholipase C system?

1. Ca2+

2. DAG

What 2 things activate protein kinase C?

phospholipase C system

The following are hormones associated with what system?

-GnRH (gonadotropin-releasing hormone)

-TRH (thyrotropin-releasing hormone)

-GHRH (growth hormone-releasing hormone)

-Angiotensin II

-ADH

-Oxytocin

ADH

What hormone uses both the phospholipase C and adenylyl cyclase systems?

intracellular side

The catalytic receptors on the cell surface are associated with enzymes located where?

guanylyl cyclase

The following are associated with what enzyme of the catalytic receptor system?

-GTP → cGMP → cGMP-dependent kinase → phosphorylates proteins

-Atrial natriuretic peptide (ANP) and nitric oxide (NO) use this enzyme system

serine/threonine kinase

The following is associated with what enzyme of the catalytic receptor system?

Use either protein kinase A or C, as well as Ca2+-calmodulin-dependent protein kinase (CaMK) and mitogen-activated protein kinases (MAPK) to phosphorylate serine and threonine

within it

Where is the tyrosine kinase activity located in the catalytic receptor itself?

3

How many domains do receptor tyrosine kinases have?

intracellular portion

When the hormone binds with the receptor tyrosine kinase, what portion of the receptor phosphorylates itself?

1. monomer

2. dimer

What are the 2 types of receptor tyrosine kinases?

tyrosine kinase activity

Tyrosine-kinase-associated receptors are associated with other proteins that have what activity?

Janus kinase family (JAK)

What is an example of proteins that have tyrosine kinase activity, associated with tyrosine kinase associated receptors?

phosphorylate itself

What cant the intracellular portion of tyrosine kinase-associated receptors do?

steroid hormones

What type of hormones utilize the intracellular receptor systems?

1. cytosolic

2. nuclear receptors

What 2 receptors are intracellular receptor systems associated with?

intracellular receptor systems

What system(s) initiate DNA transcription and synthesis of new proteins slowly?

1. Steroid hormone diffuses across membrane and binds receptor in cytosol or nucleus

2. Receptor undergoes conformational change, complex dimerizes and binds to steroid-responsive elements (SREs)

3. Complex is now a transcription factor - mRNA transcribed, translation occurs, new proteins, physiologic action

How do the intracellular receptor systems initiate DNA transcription and synthesis of new proteins?

intracellular receptor system

The following hormones utilize what receptor system?

-Glucocorticoids

-Sex hormones (Estrogen, Testosterone, & Progesterone)

-Aldosterone

-Vitamin D

-Thyroid hormones