androgen receptors

Question 1

There are several methods of hormonal therapy: tell me about them.

Answer 1

Surgical bilateral orchiectomy
Gonadotropin releasing hormone (GNRH) agonist (and now antagonists)
Anti-androgen (generally regarded as inferior to above)
Vast majority of prostate cancer patients respond to castration initially
Most develop progression despite castration by 2-3 years.

Question 2

what is the goal of endocrine therapy?

Answer 2

The goal of all of endocrine therapy is to prevent the activation of AR.

Question 3

Structure of AR

Answer 3

AR gene has 8 exons with protein length of 919 amino acids
4 structural parts to the protein
N-terminus transactivation domain (NTD)
DNA binding domain (DBD)
Hinge region
C-terminus ligand binding domain (LBD)

Question 4

how does the ar function? where does it reside?

Answer 4

The AR resides in the cytoplasm when not associated with an androgen
Testosterone is the most common androgen
Upon ligand binding inhibitory chaperones are dissociated and AR moves to the nucleus
AR undergoes homo-dimerization and binds to the androgen-responsive elements of the DNA
After binding, AR recruits co-activators and gene expression occurs.