Figure 2.

Mechanism of action and feedback loop of ADT on the hypothalamic–pituitary–gonadal (HPG) axis in the treatment of prostate cancer. Luteinizing hormone-releasing hormone (LHRH) is released from the preoptic nucleus of the hypothalamus to induce the secretion of luteinizing hormone (LH) from the anterior pituitary gland. LH moves through peripheral circulation to act on the Leydig cells of the testis, inducing release of testosterone. Testosterone promotes Pca progression by binding to androgen receptors (Ars), translocating to the nucleus, binding to androgen-responsive elements (AREs) and promoting expression of proteins involved in growth, metabolism and survival. This pathway may be disrupted by physical castration (bilateral orchiectomy) or chemical castration via LHRH agonists/antagonists, antiandrogens and CYP17 inhibitors.