Basic aspects of the control of GnRH and LH secretions by kisspeptin: potential applications for better control of fertility in females
Résumé
The neuronal control of fertility and sterility has been a subject of research for years. However, nowadays, in spite of considerable literature about GnRH during the last few decades, the precise cellular and molecular mechanisms whereby gonadal steroids and other peripheral signals converge in the brain to achieve the fine regulation of GnRH secretion remains partially unknown. In this scenario, a major breakthrough in our understanding of the neuronal signals governing reproduction took place in 2003 with the discovery of metastin/kisspeptin as a major player in the control of GnRH secretion. This molecule, first described as having a crucial role in triggering the onset of puberty, is involved in all phases of reproductive life and hence has attracted the interest of many reproductive neuroendocrinologists. Administered either centrally or peripherally, kisspeptin strongly induces the secretion of gonadotropin in many species, mainly through stimulation of GnRH secretion. Kisspeptin cells involved in the control of GnRH secretion are located in two regions of the brain: the preoptic area and the arcuate nucleus. Carrying oestradiol receptor alpha, kisspeptin cells of these regions appear to be the main integration centres for the expression of both the positive and negative feedback of steroid on GnRH secretion. More recently, this molecule has been shown to be able to synchronize preovulatory surges in cyclic ewes and cause ovulation in seasonally acyclic ewes. This review summarizes the most relevant aspects of the role of kisspeptin in GnRH/LH release and the potential application of this molecule in new strategies for controlling female fertility.