Steroids - What Are They and How Do They Work? Flashcards Preview

The Endocrine System > Steroids - What Are They and How Do They Work? > Flashcards

Flashcards in Steroids - What Are They and How Do They Work? Deck (44)
Loading flashcards...
1

Glucocorticoids signal through which receptor?

Glucocorticoid receptor (GR)

2

Glucocorticoids are dervived from what?

Cholesterol

3

What naturally secretes glucocorticoids in the body?

Zona fasciculata of adrenal glands

4

How is the release of glucocorticoid in the body regulated?

Hypothalmic-pituitary-adrenal axis

5

The availability of endogenous glucocorticoids in the body is regulated by what?

11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes

(especially 11β-HSD2)

6

What are the key differences between synthetic and natural glucocorticoids?

Synthetic glucocorticoids are:

  1. More potent
  2. Not susceptible to metabolic clearance by 11β-HSD2 
  3. Do not bind to corticosteroid binding globulin

 

7

What are the three key actions of glucocorticoids?

  1. Anti-inflammatory
  2. Anti-proliferative (aids in cancer treatment)
  3. Anti-angiogenic (aids in cancer treatment)

8

Where does the GR reside by default?

Cell cytoplasm

9

Before binding to steroids, the GR is bound to what?

Chaperone proteins

(especially Heat Shock Protein 90 (HSP90))

10

What are chaperone proteins?

Proteins which assist in conformational changes of other proteins after synthesis

They aid with unfolding and assembly/disassembly of macromolecuar structures

11

How do glucocorticoids enter a cell?

Diffusion

(they are lipophilic)

12

Describe the process which results in binding of the glucocorticoid to the GR

Glucocorticoid diffuses into cell cytoplasm

Phosphorylation and ligand binding of glucocorticoid to GR causes dissociation from accessory proteins (HSP90)

13

What are the three main reasons for the vast diveristy in GR signalling?

  1. Multiple isoforms of GR
  2. Multiple actions from different glucocorticoid response elements (GREs)
  3. Post-translational modifications of GR

14

GR is the product of which gene?

NR3C1

15

GR is a modular protein as it has many different domains. What are these 4 domains?

  1. N terminal transactivation domain
  2. Central DNA binding domain (DBD)
  3. C-terminal ligand-binding domain (LBD)
  4. Flexible "hinge region" separating the DBD and LBD

16

Why does the N terminal tranactivation domain have strong transcriptional activation functionality?

Presence of Activation Factor 1 (AF1)

17

What is the basic role of AF1?

  1. Recruit coregulators
  2. Recruit transcription machinery

18

AF1 is active independent of ligand (glucocorticoid) binding

True or false

True

(studies have shown AF1 can cause certain responses even with the complete absence of the LBD)

19

In order for Activation Factor 2 (AF2) to activate, what is required?

Ligand (glucocorticoid) binding

20

After a glucocortoid binds to the GR in the cell cytoplasm what happens?

Translocation to the nucleus

21

For what reason does glucocorticoid (ligand) binding to the GR induce translocation to the nucleus?

The DBD, hinge region and LBD possess nuclear localisation signals

This allows translocation to the nucleus via importin dependent mechanisms

22

How does the GR-Glucocorticoid complex "know" which DNA sequence to bind?

Two zinc "fingers" localised to the DBD can bind specific sequences on target genes

These specific sequences are glucocorticoid response elements (GREs)

23

Which isoforms of the GR receptors have been associated with glucocorticoid insensitivity?

  1. GRγ
  2. GR-A
  3. GR-P

24

Once translocated to the nucleus what 3 options does the GR-glucocorticoid complex?

  1. Complex binds directly to simple or negative GREs (with or without homodimerising previously)
  2. Complex binds to DNA via tethering to other transcription factors
  3. Complex binds by direct binding and interacting with other transcription factors

25

What is the outcome of the GR-Glucocorticoid complex binding to a negative GRE?

Transrepression

26

What is the outcome of the GR-Glucocorticoid complex tethering to a DNA-bound transcription factor?

Transrepression

(transcription factor activity is inhibited)

27

What is a key transcription factor which may be inhibited by glucocorticoids?

NF-kappa b

28

What is the outcome of the GR-Glucocorticoid complex binding directly to DNA with other transcription factors?

Transcription or transrepression may occur

(dependent on GRE bound to and activity of transcription factors)

29

What is TTP and what does it do?

TTP (tristetraproline)is a protein which binds to mRNA of proinflammatory genes and causes destabilisation

30

One way a GR-glucocorticoid complex can reduce inflammation is by inducing expression of what?

TTP (tristetraproline)