3 Flashcards
What classes of hormones contain non-classical hormones + examples of such hormones
1) Non-classical peptide hormones
Examples: adipokines – including leptin
2) Amino acid derivatives - neurotransmitters Examples: Melatonin, serotonin, histamine 3) Lipid hormones with membrane receptors
Examples: Eicosanoids
4) Metabolites: lactate, ketone bodies, etc.
Which cells/ organs produce non-classical hormones?
produced by diffused cells rather than an organized endocrine organ
WHat is the area of action of non-classical hormones?
non-classical hormones act locally within the tissue by which they are secreted and sometimes they also act as endocrine signals by going into circulation and affecting other tissues
Describe the location of production, storage, expression and transport of IGF-1
IGF-1 is produced mainly by the liver but produced locally buy almost all tissues
IGF-1 is not stored even though peptide hormones are normally stored in granules
IGF-1 then has to be expresses only when necessary
IGF-1 goes into the circulation as a bound hormone by transporting protein even though its a soluble hormone since it’s a peptide hormone and peptide hormones are usually transported as free hormones
Which kind of receptor is used by peptide hormones?
membrane these membrane receptors belong to the class of GPCR
Which kind of receptor is used by thyroid hormones?
nuclear
Which kind of receptor is used by steroid hormones?
nuclear
Which kind of receptor is used by eicosanoid hormones?
membrane these membrane receptors belong to the class of GPCR
Do eicosanoids belong to steroid hormones? Why?
steroid hormones are never considered to include eicosanoids because steroid hormones use nuclear receptors and eicosanoid hormones use membrane receptors just like peptide proteins
Do GPCR receptors bind to hormones only?
no, they can also bind to metabolites
DO metabolites have a signalling capacity
yes
What can medium chain FA bind to to generate a signal
to a nuclear receptors and to other FA as well
What results form GPCR mutations
diseases
Steroid hormones and thyroid hormones bind to a family of __ which are__
Steroid hormones and thyroid hormones bind to a family of intracellular receptors which are structurally related
What do nuclear receptors function as?
as transcription factors
Which receptors result in a quicker response- nuclear or membrane?
Nuclear receptor response is slow since transcription and translation of proteins is necessary
What are the classes of NR ligands?
1) classical
2) vitamins and their derivatives
3) Receptors that bind to metabolic intermediates and products
e. g FA bind to PPAR which have many isoforms each of which are expressed by different genes
What are the NR ligands belonging to vitamin group? What is their solubility?
- Vit A and Vit D
- these vitamins are lipid soluble, so these derivatives will also be lipid soluble and will bind to nuclear receptor
Describe ligands of nuclear receptors that belong to the group of metabolic intermediates and products
e.g FA bind to PPAR which have many isoforms each of which are expressed by different genes
bind to metabolites and act as metabolite sensors and lead to gene expression
Oxysterol receptors sense oxysterol concentration and thus control cholesterol metabolism by controlling gene expression as they are nuclear receptors
Why are NR ligands good drug targets?
since ligands are lipid soluble, they can be taken orally and are efficiently absorbed - almost all nuclear receptors are researched for drug targets
How can ligand levels be regulated?
- by controlling the availability fi their precursor e.g. controlling cholesterol levels to control levels of cholesterol
- synthesis
- activation (prohormone-> active hormone)
- deactivation
- elimination (hepatic, renal clearance)
Can NR ligands easily diffuse through membrane?
they are lipophilic- can diffuse in , but some times need a carrier
e.g. bile acids have to be brought into the cell by transport protein
the transporter is separated from the ligand before the binding of the ligand
what are the domains shared by all nuclear receptors?
1) AF is a domain shared by all nuclear receptors
2)a DNA- binding domain,
3)Nuclear localization signal (NLS) to be able to go into the nucleus through nuclear pore. this is a short AA sequence
NLS is a transition domain between C and D domain
3) and a ligand binding domain to be able to bind to it’s ligand
How can a new ligand for a nuclear receptor be created?
new ligand can also be created based on the ligand binding domain of that receptor to modulate it’s functioning
