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kris Endocrinology > 3 > Flashcards

3 Flashcards

1
Q

What classes of hormones contain non-classical hormones + examples of such hormones

A

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.

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2
Q

Which cells/ organs produce non-classical hormones?

A

produced by diffused cells rather than an organized endocrine organ

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3
Q

WHat is the area of action of non-classical hormones?

A

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

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4
Q

Describe the location of production, storage, expression and transport of IGF-1

A

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

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5
Q

Which kind of receptor is used by peptide hormones?

A 
membrane
these membrane receptors belong to the class of GPCR
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6
Q

Which kind of receptor is used by thyroid hormones?

A

nuclear

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7
Q

Which kind of receptor is used by steroid hormones?

A

nuclear

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8
Q

Which kind of receptor is used by eicosanoid hormones?

A 
membrane 
these membrane receptors belong to the class of GPCR
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9
Q

Do eicosanoids belong to steroid hormones? Why?

A

steroid hormones are never considered to include eicosanoids because steroid hormones use nuclear receptors and eicosanoid hormones use membrane receptors just like peptide proteins

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10
Q

Do GPCR receptors bind to hormones only?

A

no, they can also bind to metabolites

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11
Q

DO metabolites have a signalling capacity

A

yes

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12
Q

What can medium chain FA bind to to generate a signal

A

to a nuclear receptors and to other FA as well

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13
Q

What results form GPCR mutations

A

diseases

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14
Q

Steroid hormones and thyroid hormones bind to a family of __ which are__

A

Steroid hormones and thyroid hormones bind to a family of intracellular receptors which are structurally related

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15
Q

What do nuclear receptors function as?

A

as transcription factors

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16
Q

Which receptors result in a quicker response- nuclear or membrane?

A

Nuclear receptor response is slow since transcription and translation of proteins is necessary

17
Q

What are the classes of NR ligands?

A

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

18
Q

What are the NR ligands belonging to vitamin group? What is their solubility?

A
  • Vit A and Vit D

- these vitamins are lipid soluble, so these derivatives will also be lipid soluble and will bind to nuclear receptor

19
Q

Describe ligands of nuclear receptors that belong to the group of metabolic intermediates and products

A

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

20
Q

Why are NR ligands good drug targets?

A

since ligands are lipid soluble, they can be taken orally and are efficiently absorbed - almost all nuclear receptors are researched for drug targets

21
Q

How can ligand levels be regulated?

A
  • 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)
22
Q

Can NR ligands easily diffuse through membrane?

A

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

23
Q

what are the domains shared by all nuclear receptors?

A

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

24
Q

How can a new ligand for a nuclear receptor be created?

A

new ligand can also be created based on the ligand binding domain of that receptor to modulate it’s functioning

25
Q

Describe general binding of a sterol receptor to a DNA binding Domain

A

sterol receptors bind to a general sequence “AGA ACA”
steroid receptors also function as homo-dimers
steroid hormones tend to function by homo-dimerization- so you have to have 2 AGAACA sequences to allow 2 sterol receptors to bind and act as a homodimer
- steroid receptors recognize opposite orientated sequences

26
Q

Describe general binding of a non-sterol receptor to a DNA binding Domain

A

non-steroid nuclear receptors, tend to function as heterodimer and bind to “AGG TCA” sequence
recognize same sequence running in the same direction

27
Q

What are hormone response sequences

A

sequences of DNA to which hormone receptors bind

28
Q

Describe Chromatin immunoprecipitation (ChIP) Sequencing

A

fast way to recognize
antibody and antigen reactions are used for identification
chromatin - combination of DNA+ interacting protein (most likely histone)
any DNA+ protein can be called a chromatin
POI- protein of interest
protein and DNA are fixed by treating them with formaldehyde-> made more stable
when it has been stabilized you can sheer the chromatin-> cells are vibrated so they breakdown, including the chromatin
pieces of DNA are now available that have POI bound to them
we are interested in DNA with protein of interest
you need an antibody for the POI
these antibodies are attached to magnetic beads
using metal, you can pull on antibodies which will bring POI (antigen) with the bound DNA of interest to you

any protease technique can be used to destroy the protein-> pure DNA which can be but through sequencer-> you will have DNA sequences-> use computer technology to take genome sequence
the more number of genome sequences-> more DNA was pulled down
this DNA can be used as binding site for the nuclear receptors

29
Q

what are general transcription factors?

A

TF common for all gene transcription

30
Q

when nuclear receptors are not-active, they usually interact with __ and __ transcription

A

when nuclear receptors are not-active, they usually interact with co-repressors and stop transcription

31
Q

WHat does histone acetylation result in

A

promotion of gene expression

32
Q

de-acetylating enzymes are associated with__

A

de-acetylating enzymes are associated with gene expression inhibition

33
Q

What happens when ligand binds to a nuclear receptor in order to promote gene expression?

A

a ligand comes in and binds to a nuclear receptor, the dimer formed by the receptor binds to the hormone response element and brings in new protein that are called co-activators
they work with nuclear receptors and activate transcription
the enzymes that help modify histones e.g. acetyl-transferases that bring in acetyl groups and allow for gene expression
this formation of the complex allows the general transcription factor complex to be put together-> pre-initiation complex is formed as nuclear receptor is interacting with co-activator

34
Q

What are the reasons for various cell responses by different cell types to the same ligands

A
  • different types of cell express different amounts of receptors and respond to a signal differently
  • various co-activators and co-repressors are expressed
35
Q

What are the 3 types of action of synthetic ligands?

A

agonist- synthetic molecule that stimulates the activity of the protein
antagonist stops protein activity
partial-agonist- partial response is elicited, or partial activation occurs

kris Endocrinology (17 decks)

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