Question

You are a scientist on a quest to study the androgen receptor (AR) so you express it in insect cells.

1. You first add which hormone to stimulate it?
2. What are the 2 events that follow after that hormone binds to it?
3. You also see that an antagonist blocks AR DNA binding, what would be the result of adding this antagonist?

Answer 1

-testosterone, dihydrotestosterone and growth hormone,  prolactin stimulates androgen receptor in prostate of immature rats.

-primary mechanism includes gene transcription, binding results in conformational change in receptor causes dissociation of heat shock proteins , transport from cytosol to cell nucleus and dimerization. Dimer binds to specific DNA sequence called hormone response element. upregulation results in mRNA production and proteins. target genes are insulin growth factor 1, and its independent of direct binidng to its target sequence.

2nd action is non genomic which androgen receptors interact with signal transduction proteins in cytoplasm. It causes changes in ion transport and regulation of signal transduction pathways can indirectly lead to changes in gene traanscription, (phopsphorylation of other transcription factors)

-androgen receptor antagonists competitively inhibit androgen binding to androgen receptor. and this nuclear receptor has 3 domains. -ligand binding domain, DNA binding domain, and amino terminal. Evenyyts such as phosphorylation and coactivator recruitment is disrupted. steroidal AR antagonists are related to testosterone and progesterone while non steroidal are structrally distinct. steroidal have an off target hormonal actions due to their structural similarity to other steroid hormones and non steroidal are selective for AR and have no off target hormonal activity.