Androgen Receptors

Question 1

• 4 parts of the receptor? How activation works? (4 steps?
• 3 sources of testosterone?
• Cause of cancer?
• AR antagonist? Competes for? Inteferes with?

Answer 1

• N-terminus transactivation domain; DNA binding domain; hinge region; c terminus ligand binding domain
  1. ) AR-resides in cytoplasm bound to inhibitory HSP chaperone 2.) Testosterone binds and takes it to the nucleus 3.) Homodimerization and binds to coactivators 4.) gene expression
• testis (90-95%); adrenal glands (5-10%); Intracrine androgen in prostate cancer cells
• over activation of AR
• Flutamide; ligand binding domain; coactivators and binding

Question 2

• Ways to have resistance? (4)
• Key in testosterone production? Drug to block this? Advantage? Targets AR via?
  Way to target AR directly: Drug? Works how? Inibits what in pathway? (3)

Answer 2

• AR activation via non gonadal test.; over expression of AR; AR mutation leading to promiscious activation; truncated form of AR with constit. activation of AR domain
• CYP 17; Arbiraterone; blocks all 3 sources; androgen deprivation
• Enzalutamide; VERY high affinity for AR binding domain; nuclear entry; co act. recruitment; DNA binding