Nuclear hormone receptors (lecture 22) Mineralocorticosteroids and Glucocorticosteroids

Question 1

The five groups of receptors classed as NHR

Answer 1

1. Vitamin D receptors
2. Corticoid steroid receptors
3. Sex Hormone receptors
4. Thyroid Hormone receptors
5. Retinoid acid receptors
   These cards focus on corticoid steroid receptors

Question 2

NHRs in general

Answer 2

1. All NHR have lipophillic ligands (ligands that can diffuse across membranes)
2. All NHR work regulate mRNA transcription
3. Have lag periods before showing physiological changes

Question 3

NHR structure

Answer 3

Divided into the A/B, C, D, E and F domain
A/B: N-terminal, loosely folded
C: DNA binding domain (DBD)
D: Hinge domain (connecting domain between DBD and …)
E: Ligand Binding domain (LBD)
F: C-Terminal

Question 4

Wanted Affects of glucocorticoids

Answer 4

1. Up-regulation of Annexin 1 (anti-inflammatory protein)
2. Down-regulation of cyclooxyrgenase (COX2) (prevent prostaglandin synthesis)
3. Activated helper T is stopped from releasing cytokine which stops other lymphocytes from releasing interleukins (the ones that cause IgE production and eosinophil activation)

Question 5

Unwanted affects of glucocorticoids

Answer 5

1. Immunosuppression
2. Metabolic effects
3. Mineralocorticoid effects
4. Cushings syndrome

Question 6

Cushings syndrome

Answer 6

Caused by the long term use of exogenous (outside body)  glucocorticoid steroids.
Physiological effects:
1. Hypertension
2.Muscle wasting
3. pot belly
4.Poor wound healing
5. Thinning skin
Cushing can be prevented by creating drugs that are less selective for mineralocorticoids

Question 7

NHR action mechanism (transactivation)

Answer 7

1. Ligand (steroid) (L/S) diffuses across membrane
2. Binds to GCR + HSP complex
3. GCR+L/S dimerise and enters nucleus
4. Dimer works on DNA through activating RNA poly and a Coactivator and increasing mRNA transcription by binding the complex to the HRE (Hormone responsive element)

Question 8

NHR action mechanism (transrepression)

Answer 8

1. Ligand (steroid) (L/S) diffuses across membrane
2. Binds to GCR + HSP complex
3. GCR+L/S doesn’t dimerise and moves to nucleus
4. Represses transcription factor action and does not involve the complex to bind to DNA

Question 9

Steroids used for the prevention of asthma through inhalation

Answer 9

Beclomethasone
Budesonide
Fluticasone

Question 10

The use of prevention drugs through inhalation can cause oral trust and hoursness, and can be reduced by?

Answer 10

A spacer device or by mouth rinsing after use

Question 11

Negative feedback of GCS

Answer 11

The need for GCS is stimulated by Corticotrophin releasing factor (CRF) which activated Adrenocorticotrophic hormone (ACTH) to produce GCS in the adrenal cortex

Question 12

Addisonian crisis

Answer 12

The sudden stop of steroid treatement. It involves the enhancement of the naturally negative feedback system by exogenous steroids (the negative feedback never stops) so once the exogenous steroids suddenly stop, the negative feedback system prevents any steroids from being produces (endogenously)

Question 13

How can we use antibodies against asthma?

Answer 13

First of all its very expensive cuz of the production of the antibody (omalizumab)

• It prevent the IgE from binding to mast cells and eosinophil which stops them from being triggered by an antigen
• effective in medium or severe asthma