Nucleur receptor

Question 1

What are nucleur receptors?

Answer 1

Gene transcription modulating receptors, specialised transcription factors

Act by binding to consensus sequence of DNA (response elements), in promoter region of target genes as homodimer or heterodimers

Question 2

What are the properties of Ligand and drugs of nucleur receptors?

Answer 2

Ligands and drugs are highly lipophillic (hydrophobic) - to pass through membrane

cannot be ionic or polar

Question 3

What are the 3 classes of Nucleur Receptors?

Answer 3

1. Steroid Receptor Family
2. Hybrid class: thyorid/retinoid receptor family
3. Orphan receptor family

Question 4

What are the key structural features of receptor?

Answer 4

DNA binding domain, Transcriptional activation domain, Ligand binding domain

Question 5

What are some examples of Steroid Receptor Class?

Answer 5

1. Glucocorticoids (Cortsiol)
2. Mineralocorticoid (Aldosterone)
3. Estrogen
4. Progesterone
5. Androgen (Testosterone)

Question 6

What is the mechanism of action of Steroid receptors?

Answer 6

1. Steroid is transported and carried by Corticosteoird binding globin, and released into the cell
2. Binds to Glucocorticoid receptor on nucleur membrane/cytosol
3. Dimerisation (homo) and enters nucleus
4. DNA binding domai will bind to Glucorticoid response element and regulate transcription

Question 7

What are some examples of hybrid class receptors?

Answer 7

1. Thyroid receptors
2. Vitamin D receptors - 1,25-di(OH) Vitamin D3 (Calcitrol)
3. RAR (All-trans retinoic acid receptors) - All trans retinoic acid (Tretinoin)

Question 8

What are some Examples of Class 2: Orphan Nucleur receptors?

Answer 8

1. PPAR (Peroxisome proliefarator-activated receptor)
   Lysophosphatidic acid (LPA), PGI2

Question 9

How do Nucleur Receptors cause cancer?

Answer 9

Pesticide, certain chemicals constantly stimulate receptors, leading ot increase in DNA prolieration, and alteration of protein expression-> mutation and Carcinogenesis

Question 10

What is Raloxifene?

Answer 10

Bone Estrogen Receptor Agonist
Clinical use - Osteoperosis

Question 11

What is Tamoxifen?

Answer 11

Breast Estrogen Receptor Antagonist
Breast Cancer

Question 12

What are glucocorticoids?

Answer 12

Glucocorticoid receptor Agonist
Anti Inflammatory

Question 13

What is Apalutamide?

Answer 13

Androgen receptor Antagonist (class i)
Prostate Cancer

Question 14

What is Calcitrol?

Answer 14

Vitamin D3
Vitamin D receptor Agonist (hybrid clasS)
Osteoperosis

Question 15

What is Rosiglitazone?

Answer 15

PPARgamma receptor agonist (class ii Orphan)
(Peroxisome Proliferator activator receptor)

Clinical Use: Anti Type 2 Diabates Mellitus

Question 16

What is Tretinoin?

Answer 16

All trans retinoic acid receptor (RAR)
RAR receptor agonist

Clinical Use: Acne (topical)