Topic 2- Endocrine Signaling

What is signal transduction?

How receptor activation causes a physiological response

What is signal transduction specifcially?

How hormone binding to a receptor activates it and causes an endocrine response

Why is signal transduction important?

It is key to understanding physiological responses, inputs, feedback, and regulation

What are endocrine targets defined by?

Their receptor (always true for proteins and usually true for steroids)

What does hormone binding to receptors initiate?

A signal

What do all protein hormones bind to?

Receptors with binding sites on the outside of cells

What do most steroid horomones do?

Bind to receptors on the INSIDE of the cells

What do all steroid hormones regulate?

Transcription

What do all steroids regulate?

transcription

What do steroid hormones have?

nuclear receptors

What do steroid hormone-regulated transcription factors do?

Regulate DNA to RNA

What does a receptor location depend on

The hormone

What is the speed of steroid hormone transcription?

slow-can take hours, days, or lifetime

What happens when a receptor binds to a steroid hormone in the cytoplasm?

A confirmation change is induced which causes the hormone-receptor complex to enter the cell nucleus

What does the hormone-receptor complex bind to?

A 15 nucleotide DNA sequence called a Hormone Response Element

What does a Hormone reponse element do?

It causes either the formation or repression of a transcriptional complex

What happens if a transcriptional complex is formed?

mRNA transcription

What happens once mRNA is transcribed?

The mRNA is processed and leave the nucleus

What is mRNA translated on ?

Ribosomes in the cytoplasm, leading to changes in protein levels

What is the ultimate response of steroid regulated transcription?

Change in the levels of specific proteins

What does transcriptional repression lead to?

Protein degradation (turnover)

What does transcriptional regulation by steroid hormones lead to?

Slow increases or decreases in the amount of specific cellular proteins that leads to a response dependent about the activity of proteins

What do some steroids bind to?

Cell surface receptors

What is the reponse time like for steroids the bind on the outside?

Responses are much faster than transcription mechanisms

What do protein hormones always bind to?

cell surface receptors

What do protein hormones binding to the receptor create?

Intracellular signals that target specific proteins

What is the response time of protein hormone signal transduction?

Very rapid- seconds to minutes

What creates a slow physiological response when it comes to protein hormone signal transduction?

When specific target proteins indirectly regulate transcription

What does response time depend on?

The hormone and its target

What are most protein hormone receptors?

g-protein coupled

What do G-protein coupled receptors do?

G-protein complex is activated through a hormone receptor which interacts with an effector protein to turn on a signal transduction pathway

What does GPCR regulate?

Serine/threonine kinase that phosphorylates other proteins

What does GPCR initate?

A second messenger response

What are tyrosine kinase receptors?

Less common receptors that phosphorylates proteins at amino acid tyrosine to lead to an endocrine response

Why are tyrosine kinase linked receptors important?

They play an important role in cell growth and cell proliferation

What will a hormone never bind to?

BOTH a GPCR and TK-liked receptor

What does protein hormone transcription always start with?

Cell surface receptors that can be both TK and G-protein coupled

What can protein hormones also do to transcirption?

repress it

What does protein hormone transcription do?

Regulates protein synthesis

What are the two key second messengers for GPC receptors?

Calcium and cyclic AMP

What is calcium-regulated by?

Gq class that releases calcium from internal stores

What can directly binding to calcium do?

Activate targets

What does calcium do to protein hormones?

It phosphorylates proteins to initiate a response

What does cyclic AMP do?

activates protein kinases to phosphorylate proteins that leads to a reponse

What can GPC receptors regulate?

hormone exocytosis

How do GCP receptors regulate exocytosis?

Calcium and cyclic AMP activate kinases which serve as the signal to release the contents of the exocytotic vesicle

What does Gs do?

Stimulates cAMP which activates protein kinases

What does Gi do?

It inhibits cAMP synthesis

What does Gq do?

It activates protein kinases and binds to proteins

What are the responses of second messengers?

they regulate enzyme activity and regulate transcription facors

What can transcription factors modify?

Gene expression and protein synthesis

What is the timing of protein hormone signaling mechanism?

Fast and temporary as there is a direct modifaction to proteins

Why is the singaling mechanism of steroids slow?

Transcription of DNA can take several hours

There are over 1000 influencing genes

Can be irreversible

What regulates the response of a target?

Receptor diversity and hormone interactions

What does receptor diversity dictate?

Target response

What do hormones have many of?

Targets and responses

How many receptors can a hormone have?

More than one

What are receptors specific to?

The tissues in which they are located

What does epinephrine do when bound to the alpha 1 receptor in the intestinal blood vessel

Constrict

What does epinephrine do in the beta-2 receptor in the skeletal blood vessel?

Dilate

What do antagonists hormones do?

They have opposite effects and work against each other

What is an example of antagonist hormones?

Insulin vs Glucagon

What are synergist hormones?

Hormones that work together to create a greater effect

What is synergism likely the result of?

Different signaling mechanisms working together

What does antagonism adjust to?

homeostasis

What are the signal properties of steroid hormones?

Diffusion into the cell nucleus and conversion to an active form in the target tissue