androgen receptos clincal vignette

Question 1

Sources of androgen in body relevant to prostate cancer

Answer 1

1. testis
2. adrenal glands
3. intracrine androgen production

Question 2

testis are responsible for ____%

Answer 2

90-95% systemic production

Question 3

adrenal glands are responsible for ___%

Answer 3

5-10%

systemically

Question 4

intracrine androgen production

Answer 4

testosterone is produced in the prostate cells themselves

Question 5

The AR resides in the_____

Answer 5

cytoplasm when not associated with an androgen

Question 6

____ is the most common androgen

Answer 6

testosterone

Question 7

Upon ligand binding, inhibitory chaperones are _____ and AR ____

Answer 7

dissociated

AR moves into nucleus

Question 8

AR undergoes ____ in the nucleus

Answer 8

homodimerization and binds to the androgen responsive elements of the DNA

Question 9

After binding to the DNA, AR then ____

Answer 9

recruits co-activators and gene expression occurs

Question 10

Mechanisms of resistance to hormone therapy in PCA

Answer 10

1. AR activation via non-gonadal testosterone
2. Overexpression of AR
3. AR mutation leading to promiscuous AR activation
4. Truncated form of AR, with constitutive activation of the ligand binding domain

Question 11

The microsomal enzyme ______ plays a key role in androgen production

Answer 11

cytochrome P (CYP) 17

Question 12

Abiraterone is a _____

Answer 12

1. specific and potent inhibitor of CYP 17

2. blocks testosterone from all 3 sources

Question 13

enzultamide type of drug

Answer 13

antiandrogen

Question 14

Enzalutamide mechanism of action

Answer 14

1. Inhibits nuclear translocation
2. Inhibits Co-activator recruitment
3. Inhibits DNA binding of AR