Sex Requires Kisses

Imagine a disease that prevents you from having biological children of your own. Hypogonadotropic hypogonadism is characterized by defects in gonadal development, which results in infertility or in failure to go through puberty (1). A deficient production of follicle-stimulating hormone (FSH) and lutinizing hormone (LH) causes the disease (1). Tassigny et al., (2007) made a major discovery about the disease, showing that Kiss1 activates GPR54, a receptor involved in causing hypogonadadotropic hypogonadism (2). In 2003, two independent research laboratories identified mutations in GPR54, a G protein-coupled receptor gene, which causes idiopathic hypogonadadotropic hypogonadism in both humans and mice (1, 3). Deleting GPR54 in mice resulted in underdeveloped reproductive organs in both female and male mice (3,4). Male mice had low levels of testosterone, while females had low levels of reproductive hormones (3,4). Previously, the studies showed that GPR54 is vital for the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which induces secretion of LH and FSH hormones from the anterior pituitary (5). The biological role of LH and FSH hormones is to stimulate the development of reproductive organs. Kiss1 was initially discovered as a tumor suppressor gene (6). Kiss1 encodes for the protein kisspeptin-54, also known as metastin due to its ability to delay metastasis (6). In addition, studies also show that exogenous delivery of kisspeptin-54 stimulates the hypothalamamic-pituitary gonadal axis and the secretion of both LH and FSH hormones in mice (6, 7). Kiss-1 mRNA has been located in the rostral caudal area of the hypothalamus (6, 8). Also, scientists demonstrated that kisspeptins activate GnRH neurons at puberty in female and male mice (9). Until the discovery of Tassigny et al., it was not known what stimulates GPR54. Scientists hypothesized that Kiss1 is a ligand for GPR54, since both seem to modulate the release of FSH and LH, hormones that are crucial for gonadal development. In addition, the exact physiological role of Kiss1 was unknown. To test the hypothesis that Kiss1 is a true ligand for GPR54, Tassigny et al., generated Kiss1 deletion mice. Kiss1 knockout mice, mice that do not express the Kiss1 gene, were created by deleting two exons in the Kiss1 gene located on chromosome 1. Scientists inserted the LacZ reporter gene into one of the deleted Kiss1 exons in order to confirm the deletion of the Kiss1 gene. After confirming the deletion of the Kiss1 gene, scientists began to look at the anatomy and histology of the mice. Because the physiological role of the gene was unknown, scientists looked into this subject. As expected, mutant mice only had ________________________________________________