Embryo implantation and GnRH antagonists - The search for the human placental GnRH receptor

Hypothalamic gonadotrophin-releasing hormone (GnRH) plays a major role in t he endocrine control of reproduction. Acting through its high affinity rece ptors on pituitary gonadotrophs, it regulates the secretion of gonadotrophi ns. In addition, GnRH also functions as a local regulator in a number of ot her cell lines and tissues, including the placenta. In a manner analogous t o hypothalamic GnRH stimulation of LH and FSH from the anterior pituitary, GnRH was found to cause a dose-dependent release of human chorionic gonadot rophin (HCG) from the placenta. So began the search for a putative GnRH rec eptor in the human placenta. Although early radio-receptor studies reported specific binding, the properties of these 'putative' GnRH binding sites we re found to differ significantly from those of their pituitary counterparts in several important respects. This was followed by a series of contradict ory reports that led to more questions and opened up avenues for further in vestigations. Even after nearly two decades of research, the human placenta l GnRH receptor has not been characterized beyond all reasonable doubt. Thi s review recalls the discovery, the controversies and unanswered questions concerning the human placental GnRH receptor.