Androgen receptor

Question 1

source of androgen in the body

Answer 1

testicles, adrenal gland, Intracrine androgen production in prostate cancer cells

Question 2

structure of androgen receptor

Answer 2

AR gene has 8 exons with protein length of 919 AA. 4 structural parts: N-terminus transactivation domain (NTD), DNA binding domain (DBD), Hinge region, C-terminus ligand binding domain (LBD)

Question 3

function of androgen receptor

Answer 3

AR resides in cytoplasm, testosterone is most common androgen, ligand binds => inhibitory chaperones dissociate and AR moves to the nucleus => undergoes homo-dimerization and binds to androgen-responsive elements onDNA => AR recruits co-activators and gene expression occurs

Question 4

resistant to endocrine therapy for prostate cancer

Answer 4

AR activation via non-gonadal testosterone, overexpression of AR, AR mutation leading to promiscuous AR activation, truncated AR with constitutive activation of the ligand binding domain

Question 5

enzalutamide

Answer 5

new generation antiandrogen, inhibits nuclear translocation, inhibits Co-activator recruitment, inhibits DNA binding of AR, no known partial agonist properties seen with 1st gen antiandrogens such as bicalutamide

Question 6

abiraterone

Answer 6

reduces testosterone to 0