Hormones, receptors & hormone signalling Flashcards
What is the definition of hormones?
- chemical messangers carried in the blood stream from the site of synthesis (ie endocrine gland) to the site of action (target tissue)
What are the 3 major hormone classes?
- Peptide hormones
- Amine hormones
- Steroid hormone
What are examples of amine hormones?
- catecholmines eg NA and Adr
- Thyroid hormones
What are examples of steroid hormones?
- androgens/ estrogens/ progestagens
- corticosteroids
- Vit D
**Describe **peptide hormones
- most abudant class
- water soluble - therefore easily transported in the blood but DO NOT cross cell membranes readily
- synthesised on the rough ER
- stored in secretory vesicles
- hormone is** processed intracellularly and extracellularly**
What is an example of a peptide hormone processing?
preproglucagon
* this is a precursor of glucagon
* generated in the alpha cells of the pancreas and the L cells of the intestine
What substance are all the hormones in the class amines derived from?
the amino acid -** tyrosine**
Where is noradrenaline produced & what cells is it produced by?
- in the** medulla** of the adrenal gland
- synthesised by the chromaffin like cells
is noradrenaline water soluble?
- yes noradrenaline is water soluble - therefore is readily soluble and easily transported in blood
where is thyroid hormone stored?
the colloids
Which** three plasma proteins** function to transport thyroid hormones & which has the highest affinity?
- thryroxine binding globulin (TBG)
- Transthyretin
- Albumin
however TBG has highest afinity
which thyroid hormone is more biologically active?
T3
* T4 is converted to T3 - which is the biologically active hormone that regulates your bodies metabolism
What are all steroid hormones derived from?
- cholesterol
are steroid hormones stored?
No they are not stored but they are immediately released from cell after synthesis
are steroid hormones water soluble?
NO
* they are extremely hydrophobic (ie not water soluble)
* they can freely diffuse across plasma membrane at site of synthesis and site of action
* require plasma transport proteins to reach target cell
Do steroid hormones have a longer half life than peptide hormones?
yes - longer half life and slower acting
How do receptors bind to hormones?
- they bind with** high specificity & affinity**
- the interaction is reversable
What is the binding affinity of the receptor known as?
- equilibrium constant called **Kd or the dissociation constant **
what does a **low vs high dissociation constant **mean for the affinity of the receptor?
- the lower the Kd, the greater the hormone binding affinity
Compare upregulation vs downregulation of receptors
-
Upregulation involves the increase in the number of receptors due to external stimulation
* downregulation involves the decrease in the number of receptors eg when receptors have been chronically exposed to an excessive amount of hormones
Describe the **steps of the mechanism of action **of a steroid hormone
- lipid soluble hormones passes freely through cell membrane
- hormone binds to receptor in the cytoplasm- forming a receptor -hormone complex
- receptor hormone complex enters the nucleus and binds to another receptor on the chromatin
- transcribed mRNA is translated into proteins that alter cell activity
Describe the** mechanism of action** of the thyroid hormone and it’s receptor
- the thyroid hormone receptor is a transcription factor (ie it regulates the expression of genes)
- without the thyroid hormone, the receptor forms a homodimer with another thyroid hormone receptor
- thyroid hormones enter the cell through certain receptors and T4 converted into T3
- T3 enters the nucleus and binds to the receptor
- co repressor is released and co activator binds to this complex and activates gene transcription
Describe the structure of G protein coupled receptors?
- 7 transmembrane domains
- 3 subunits - G alpha, beta and gamma
- Galpha binds to GDPin inactive state and becomes activated by exchange of GDP for GTP
Describe how G proteins work
- binding of the hormone induces a conformational change in the receptor
- the activated receptor **binds to the Ga subunit **
- activated receptor causes conformational change in Ga, triggering dissociation of GDP
- **binding of GTP to Ga **triggers dissociation of of Ga from the receptor and Gby
- hormone dissociates from G receptor , Ga binds to effector and activates it
- hydrolysis of GTP to GDP causes Ga to dissociate from effector and reassociate with GBy
What are** tyrosine kinase receptors**?
- receptors that contain tyrosine kinase enzyme - an enzyme that adds a phosphate group to a tyrosine residue of a substrate protein
- most must dimerise before they become functional
Describe** JAK-STAT signalling** (tyrosine kinase)
- 2 cytokine receptors are associated with 2 JAK proteins
- when a ligand binds to cytokine receptor, it changes the conformation of the receptor and brings close together
- one JAK protein phosphorlyates the other
- the phosphorlyated JAK proteins phosphorlyate the tyrosine cytokine receptors
- the phosphorlyated receptor DOCKS to stats protein
- the Stat proteins dimerise and translocate to the nucleus, bind to DNA and activate gene transcription
what are 3 main examples of second messangers?
- cAMP
- Ca2+
- phospholipids ( IP3 and DAG)
What is the function of protein kinases (A & C)?
- they are enzymes that add a phosphate group to another protein
- they are activated by 2nd messangers
what does PKC require for maximal activity?
- requires Ca2+ and DAG
what does PKC require for maximal activity?
- requires Ca2+ and DAG
