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The classical mammalian form of gonadotropin releasing hormone (GnRH), GnRH I, is a hypothalamic neuropeptide that functions as a key regulator of reproduction. The interaction between GnRH I and its receptor, GnRH receptor I (GnRHR I), stimulates gonadotropin secretion from the anterior pituitary gland. The gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), act on the gonads to stimulate either steroidogenesis and ovulation or gametogenesis, respectively. The steroid hormones produced in the gonads act through a feedback pathway to regulate the production of both GnRH I from the hypothalamus and gonadotropins from the anterior pituitary.
Another form of GnRH, GnRH II, has recently been discovered. This isoform differs from GnRH I by 3 amino acids and is highly conserved from bony fish to man (Neill, 2001). Like GnRH I, the GnRH II ligand has been implicated in reproduction. In the rhesus monkey, GnRH II can induce LH and FSH production (Densmore and Urbanski, 2003). Furthermore, administration of GnRH II to mice and musk shrews resulted in rescued reproductive behavior in nutritionally deprived females, demonstrating that GnRH II is correlated with energy balance and reproduction in females (Kauffman et al., 2004; 2006). In male reproduction, GnRH II is involved in steroidogenesis as GnRH II agonist treatment of murine Leydig cells increased testosterone production and expression of the steroidogenic enzymes, steroidogenic acute regulatory protein (StAR), P450c and 3β-hydroxysteroid dehydrogenase (3β-HSD; Lin et al., 2008). Also, boars immunized against GnRH II had decreased gonadotropin secretion and the Leydig cells had reduced ability to respond to LH challenges, indicative of a role in both gonadotropin release and Leydig cell function (Bowen et al., 2006).