Current and future applications of GnRH, kisspeptin and neurokinin B analogues

Abstract

Reproductive hormones affect all stages of life from gamete production, fertilization, fetal development and parturition, neonatal development and puberty through to adulthood and senescence. The reproductive hormone cascade has, therefore, been the target for the development of numerous drugs that modulate its activity at many levels. As the central regulator of the cascade, gonadotropin-releasing hormone (GnRH) agonists and antagonists have found extensive applications in treating a wide range of hormone-dependent diseases, such as precocious puberty, prostate cancer, benign prostatic hyperplasia, endometriosis and uterine fibroids, as well as being an essential component of in vitro fertilization protocols. The neuroendocrine peptides that regulate GnRH neurons, kisspeptin and neurokinin B, have also been identified as therapeutic targets, and novel agonists and antagonists are being developed as modulators of the cascade upstream of GnRH. Here, we review the development and applications of analogues of the major neuroendocrine peptide regulators of the reproductive hormone cascade: GnRH, kisspeptin and neurokinin B.