Mutual Regulation By GnRH and Kisspeptin of Their Receptor Expression and Its Impact on the Gene Expression of Gonadotropin Subunits

Presentation Number: SUN 479
Date of Presentation: April 2nd, 2017

Haruhiko Kanasaki*1, Aki Oride2, Tomomi Hara3 and Satoru Kyo3
1Shimane Univ Sch of Med, Izumo Shimane, Japan, 2Shimane University, Izumo, Japan, 3Shimane University School of Medicine, Izumo, Japan


Hypothalamic kisspeptin plays a pivotal role in the regulation of the hypothalamic-pituitary-gonadal axis by stimulating gonadotropin-releasing hormone (GnRH) release into the portal circulation, with the subsequent release of gonadotropins. Kisspeptin and its receptor, the Kiss 1 receptor (Kiss1R) are also expressed in the pituitary gland. This study demonstrates the interaction between GnRH and kisspeptin within the pituitary gonadotrophs by altering their individual receptor expression. Kisspeptin and Kiss1R were expressed in pituitary gonadotroph cell lines, LβT2. Endogenous Kiss1R did not respond to kisspeptin and failed to stimulate gonadotropin LHβ and FSHβ expression in LβT2 cells; however, kisspeptin increased both LHβ and FSHβ promoter activity in Kiss1R-overexpressing LβT2 cells. Stimulating the cells with GnRH significantly increased Kiss1R expression, whereas kisspeptin increased the expression of the GnRH receptor (GnRHR) in these cells. Elevating the Kiss1R concentration led to an increase in the basal activities of gonadotropin LHβ- and FSHβ-subunit promoters. In addition, the level of kisspeptin-induced LHβ promoter activity, but not FSHβ, was significantly increased when a large number of Kiss1R expression vectors were introduced into the cells. The level of induction of GnRH-induced gonadotropin promoter activities was not significantly changed by increasing Kiss1R expression. Increasing the amount of GnRHR by overexpressing cellular GnRHR did not potentiate basal gonadotropin promoter activities; however, kisspeptin and GnRH stimulated increase of gonadotropin promoter activities were significantly potentiated (except GnRH-induced LHβ promoters). Our current observations demonstrate that GnRH and kisspeptin affect each other’s function to stimulate gonadotropin subunit gene expression by reciprocally increasing the expression of their receptors.


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