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Luteinizing hormone‐releasing hormone (LHRH) receptor agonists vs antagonists: a matter of the receptors?

Luteinizing hormone‐releasing hormone (LHRH) agonists and antagonists are commonly used androgen deprivation therapies prescribed for patients with advanced prostate cancer (PCa). Both types of agent target the receptor for LHRH but differ in their mode of action: agonists, via pituitary LRHR receptors (LHRH‐Rs), cause an initial surge in luteinizing hormone (LH), follicle‐stimulating hormone (FSH) and, subsequently, testosterone. Continued overstimulation of LHRH‐R down‐regulates the production of LH and leads to castrate levels of testosterone. LHRH antagonists, however, block LHRH‐R signalling causing a rapid and sustained inhibition of testosterone, LH and FSH. The discovery and validation of the presence of functional LHRH‐R in the prostate has led to much work investigating the role of LHRH signalling in the normal prostate as well as in the treatment of PCa with LHRH agonists and antagonists. In this review we discuss the expression and function of LHRH‐R, as well as LH/human chorionic gonadotropin receptors and FSH receptors and relate this to the differential clinical responses to agonists and antagonists used in the hormonal manipulation of PCa.