ABSTRACT
Gonadotropin-releasing hormone (GnRH), the first key hormone of reproduction, is synthesized in some 1000 neurons in the hypothalamus and is released in a pulsatile manner (every 30-120 min, according to the species) to stimulate pituitary gonadotrophs for luteinizing hormone (LH) and follicle stimulating hormone (FSH) synthesis and release. The twenty-three structural variants of GnRH, described in protochordates and vertebrates, evolved over some 550 million years of evolution. The earliest evolved forms of GnRH are the octopus, sea squirt (Ciona) and chicken GnRH-II, which is conserved from bony fish to man. In many vertebrates, three forms of GnRH and three cognate receptors have been described, with GnRH-I (GnRH) regulating the hypothalamo-pituitary axis and gonadotropin release and synthesis. GnRH-II, with a wide distribution in the central and peripheral nervous system, is thought to have a role as a neuromodulator affecting reproductive behavior, and GnRH-III (salmon GnRH) functions only in teleost1. Although three cognate receptors have evolved, in man and several other species GnRH-I and -II interact with the type I GnRH receptor (GnRHR)1. The binding of GnRH to GnRHR results in receptor activation and initiation and propagation of intracellular signaling. It is thought that different GnRH ligands, both agonists and antagonists, can determine preferential interactions with different intracellular protein complexes through stabilization of the GnRHR in different conformations, leading to the activation of specific signal transduction pathways. Here we focus on
GnRH-I (GnRH), interaction with GnRHR-I (GnRHR), and the signaling leading to gonadotropin release and in particular to gonadotropin synthesis.
