What Is the Androgen Receptor? A Key Molecule in Prostate Cancer Development

The androgen receptoris the molecule playing the most important role in prostate cancer development. Prostate cancer cell genetic and proteomic analyses have shown that androgen receptor activityis very high. Let’s explore this receptor, which is crucial in prostate cancer and is targeted by medicines used clinically against the disease.

Under normal conditions, the androgen receptor is responsible for prostate development and maintenance. It initiates the androgen signaling pathway. The figure below explains how this pathway works.

T: testosterone; DHEA: dehydroepiandrosterone; DHT: dihydrotestosterone; AR: androgen receptor; hsp: heat shock protein

Androgens (male sex hormones)are present in both sexes, at much higher levels in men, and are produced in the adrenal glands and testes. Unlike many receptors, androgen receptors are located inside cells, in the cytoplasm, rather than on the cell membrane. Molecules that activate them are called androgens. The most abundant circulating androgen is testosterone. Most testosterone is produced in the testes, with a small amount made by the adrenal glands. After testosterone and another precursor, dehydroepiandrosterone (DHEA), enter the cell, 5 alpha-reductase converts them into dihydrotestosterone (DHT). When inactive, the androgen receptor is bound to heat shock proteins. DHTbinds to the androgen receptor, causing heat shock proteins to detach. Activated receptors travel to the nucleus and attach to androgen receptor-associated regions in DNA. This activates genes responsible for cell proliferation, such as thePSA gene . The androgen signaling pathway maintains the prostate gland.

Excessive androgen receptor activation causes uncontrolled cell proliferation. This receptor is fundamental to the onset of prostate cancer.

Why Is the Androgen Receptor Important in Prostate Cancer?

• Clinically used hormone-suppressing prostate cancer medicines target androgen synthesis and the androgen receptor. They are part of androgen deprivation therapy.
• Androgen receptors are highly active in prostate cancer. After androgen deprivation treatments, such as antiandrogen medicines or castration, blood androgen levels and receptor activity fall.
• Approximately 20 percent of prostate cancer patients are diagnosed at an advanced stage. In these patients, disease recurs within 2 years after hormone suppression and becomes drug-resistant. This is called castration-resistant prostate cancer . In this condition, intracellular androgen signaling remains active even without enough external testosterone to stimulate the receptor. Receptor mutations, androgen receptor gene variants, and sensitivity to low testosterone contribute to this activation. Recent research has shown that AR variants cause resistance to prostate cancer medicines.

In our next article, you can explore the genetic changes that activate the androgen receptor in prostate cancer.

Related Topics:

• Advances in Prostate Cancer Treatment—2017 and 2018
• Which Treatment Should Be Chosen for Newly Diagnosed Stage 4 Prostate Cancer?