Reproductive functions are maintained by a complex hormonal regulatory network called the hypothalamic–pituitary–gonadal (HPG) axis, which is under the hierarchical control of a network of neurohormones that ultimately modulate the synthesis and pulsatile release of the decapeptide gonadotropin-releasing hormone (GnRH) by specialized neural cells distributed along the mediobasal hypothalamus. This neuropeptide drives the production of the two gonadotropic hormones of the anterior pituitary gland, luteinizing hormone (LH) and folliclestimulating hormone (FSH), which are released into the circulation and regulate specific functions of the ovary and testis. In turn, hormones produced by the gonads feed back to the hypothalamic– pituitary level to maintain functional balance of the HPG axis, through negative and positive (only in females) regulatory loops. In this article, we review the main hormonal regulatory systems that are operative in the HPG axis with special emphasis on recent developments in our knowledge of the neuroendocrine pathways governing GnRH secretion, including the identification of kisspeptins and G-protein-coupled receptor 54 (GPR54) as major gatekeepers of puberty onset and fertility.

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