MON-LB082 Elevated Expression of KISSR Is Associated with Secretory Function of Functioning Gonadotroph Adenomas

Abstract

Background: Gonadotroph adenomas are identified as the most common histological subtype of pituitary adenomas. But overwhelming majority of them are hormonally silent and act as non-functioning pituitary adenomas that presenting only with mass effects. The rest few named functioning gonadotroph adenomas (FGAs) can secrete biologically active gonadotropins and lead to characteristic abnormities of the hypophysial-gonadal axis function, such as isosexual precocious puberty in children, ovarian hyperstimulation and menstrual irregularity in premenopausal women and testicular enlargement in men. The mechanism remains unknown why FGAs have different secretory function from the clinical non-functioning ones which are morphologically same. Kisspeptin secreted by KISS1 neurons on hypothalamus can stimulate GnRH secretion when combines with its receptor KISS1R. Objective: To investigate whether kisspeptin and KISS1R are of effect for the secretory function of FGAs. Methods: we studied 18 clinically and histologically verified pituitary adenoma tissue samples: Group I(3 FGAs including 2 females and 1 male) ,Group II(12 NFPAs with immunohistochemistry positive for FSH and/or LH)and Group III(3 NFPAs with immunohistochemistry negative for FSH and LH). The mRNA expression levels of Kisspeptin and KISS1R were measured by RT-qPCR and the protein expression of KISS1R were determined by Western bolt. We also sequenced KISS1R gene in sera of all 3 FGAs patients and 2 female FGA stissue samples. The DNA methylation analyses of KISS1R promoter region in PA tissues were also performed. Results: We found that the KISS1R mRNA level was significantly different among three groups(p<0.05): Group I was highest,which was 1.8 times as Group II and 8.5 times as Group III. But there was no difference of Kisspeptin mRNA level among the groups. Western bolt showed that the KISS1R protein level was also significantly up-regulated in FGA group than the other two groups(p<0.05). A missense change c.1091T>A in exon 5 of KISS1R gene was found in the both female FGA pituitary adenoma DNA while no mutations of this gene were found in the serum samples of 3 FGA patients. No DNA methylation differences of KISS1R promoter region were observed among the three groups. Conclusion: We speculate that the elevated expression of KISS1R could play a role in the secretion function of FGAs. The expression of KISS1R might need to achieve to a certain threshold that could bring the secretory ability of FGAs. Sources of Research Support: The National Key Research and Development Program of China” (No. 2016YFC0901501) and CAMS Innovation Fund for Medical Science (CAMS-2016-I2M-1-002) awarded to HJZ. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.