nuclear Receptor Flashcards
how many classes are there for nuclear receptors
steriod reecptor family
thyroid/retinoid receptor family
orphan receptor family
binding domains of the nuclear receptor
ligand binding,
dna binding with zinc fingers
trasncription activating
class 1 steriod receptors
what are they and their ligand and drug s
glucocorticoid receptor
- cortisol
glucocorticods
mineralocorticoids receptor
- aldosterone
fludrocortisone
estrogen recepptr
estradiol
estrogen
progestrone recep
progesterone
progestins
androgen receptor
testosterone
what happens to the steroid that binds to the glucocorticoid receptor
dimerisation of the receptors
Hybrid Class: Thyroid/Retinoid Receptors
Thyroid Receptor (TR)
Triiodothyronine (T3) / thyroxine (T4)
(Drug: Levothyroxine)
Vitamin D Receptor (VDR)
1,25-di(OH) Vitamin D3 (Drug: Calcitriol)
RAR (all-trans retinoic acid receptor)
All-trans Retinoic Acid (Drug: Tretinoin)
Retinoic X Receptor (RXR)
9-cis Retinoic Acid (Drug: Bexarotene)
Class II: Orphan Nuclear Receptors
PPAR (peroxisome proliferator-activated receptor)
Lysophosphatidic acid (LPA), PGI2, LTB4
LXR (liver-X-Receptor)
Hydroxycholesterol
SXR (steroid and xenobiotic receptor)
Pregnanolone, Therapeutic drugs
AhR (Aryl hydrocarbon receptor)
Bilirubin, Aromatic hydrocarbons (e.g. benzo(a)pyrene), Dioxin
FXR (farnesoid-X-receptor)
Chenodeoxycholic acid
CAR (constitutive androstane receptor)
Androstanol
Nuclear Receptor: Mechanism for Carcinogenesis
ERα
Fulvestrant
(Selective Estrogen Receptor Degrader)
AR
Abiraterone
(Testosterone Synthesis Inhibitor)
Apalutamide
(2nd generation Androgen Receptor Blocker)
what is the effect of nuclear receptor mechanism for carcinogenesis
degradation of the receptors
dimerisation of the nuclear receptors
class 1: homodimer
hubrid class: heterodimers
class 2: heterodimers
Different Modes of Activation: Estrogen Receptor
Genomic
tethered, where they bind to other trasnscription factors
non genomic :
ligand independent: even in absence of the ligand the receptors dimerise and bind to the DNA
Ligand (Agonist) Clinical Use
GR
Cortisol
Glucocorticoids
Endocrine
Anti-inflammatory
MR
Aldosterone
Fludrocortisone
Na+/H2O Balance
ER
Estradiol
Raloxifene/Tamoxifen
(bone ER)*
HRT
Osteoporosis
PR
Progesterone
Progestins Oral Contraceptive
AR
Testosterone HRT
VDR
1,25-(OH)2 Vitamin D3
Calcitriol
Ca++ Homeostasis
Osteoporosis
TR
Triiodothyronine (T3)
Levothyroxine
Thyroid Replacement
Therapy
Antagonist Clinical Use for each nuclear receptor
GR : Mifepristone
Cushing’s Syndrome
MR:Spironolactone Aldosteronism
ER:Tamoxifen/
Raloxifene
(breast ER)*
Breast Cancer
PR:Mifepristone Abortifacient
AR:Flutamide Prostate Cancer
Nuclear reecptor PPARy and RAR Agonist
Rosiglitazone
Anti-Type 2 Diabetes Mellitus
(↑heart attacks, strokes & heart failure)
Tretinoin
Acne, blood cancer (e.g. leukemia)
