Gonadotropin-releasing hormone (GnRH) and its natural analogues: a review

The pivotal role of gonadotropin-releasing hormone (GnRH) during the hormonal regulation of reproductive processes is indisputable. Likewise, many factors are known to affect reproductive function by influencing either GnRH release from hypothalamus or pituitary gland responsiveness to GnRH. In veterinary medicine, GnRH and its agonists (GnRHa) are widely used to overcome reduced fertility by ovarian dysfunction, to induce ovulation, and to improve conception rate. GnRHa are, moreover, integrative part of other pro-fertility treatments, e.g. for synchronization of the estrous cycle or stimulation for embryo transfer. Additionally, continuous GnRH which shows desensitizing effects of the pituitary-ovarian axis has been recommended for implementation in anti-fertility treatments like inhibition of ovulation or reversible blockade of the estrous cycle. Just as much, another group of GnRH analogues, antagonists, are now in principle disposable for use. For a few decades, GnRH was thought to be a unique structure with a primary role in regulation gonadotropins. However, it became apparent that other homologous ligands of the GnRH receptor (GnRHR) exist. In the meantime, more than 20 natural variants of the mammalian GnRH have been identified in different species which may compete for binding and/or have their own receptors. These GnRH forms (GnRHs) have apparently common and divergent functions. More studies on GnRHs should contribute to a better understanding of reproductive processes in mammals and interactions between reproduction and other physiological functions. Increased information on GnRHs might raise expectations in the application of these peptides in veterinary practice. It is the aim of this review to discuss latest results from evolutionarily based studies as well as first experimental tests and to answer the question how realistic might be the efforts to develop effective and animal friendly practical applications for endogenous GnRHs and synthetic analogues.