Estradiol-dependent and ?independent upregulation of Kiss1 in the amygdala, BNST and septum of mice.

STEPHENS SBZ; PASRRA N; BIZZOZZERO MARIANNE; KAUFFMAN, ALEXANDER S; DI GIORGIO NP; YANG J; CHAHAL, R; LIAW, M; LIBERTUN CARLOS; LUX LANTOS, V.

Congreso; 9th International Congress of Neuroendocrinology; 2018

Estradiol-dependent and -independent upregulation of Kiss1 in the amygdala, BNST, and septum of miceShannon B.Z. Stephens1*, Noelia P. Di Giorgio2*, Jennifer Yang1, Ruby A. Parra1, Navdeep Chahal1, Reanna B. Liaw1, Marianne Bizzozzero Hiriart2, Carlos Libertun2, Victoria A. Lux-Lantos2, Alexander S. Kauffman11Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA 2Institute of Biology and Experimental Medicine?CONICET, Buenos Aires, Argentina *These authors contributed equally.Kisspeptin, encoded by Kiss1, stimulates GnRH release. Kiss1 neurons reside in the hypothalamic AVPV/PeN and ARC nuclei, and in smaller numbers in extra-hypothalamic areas, including the medial amygdala (MeA), bed nucleus of the stria terminalis (BnST), and lateral septum (LS). We previously demonstrated that: 1) MeA Kiss1 expression is essentially undetectable in the absence of sex steroids and stimulated by estradiol (E2) acting via ERalpha; and 2) gonad-intact GABABRKO mice have much greater Kiss1 expression in the MeA, BnST, and LS than WT littermates. However, it is unknown which estrogen receptor subtype mediates E2?s upregulation of BnST and LS Kiss1 expression or if Kiss1 levels in the MeA, BnST, and LS are still elevated in GABABRKO mice even without sex steroids. Here we used in situ hybridization to compare Kiss1 expression in the MeA, BnST, and LS of gonadectomized and gonadectomized+E2 ERaKO, BERKO, GABABRKO, and WT mice. We found that E2 treatment increases BnST and LS Kiss1 expression in WT and BERKO mice, but not in ERaKOs, indicating Kiss1 expression in these regions is upregulated specifically via ERalpha pathways. Next, we found that, unlike gonadectomized WTs, gonadectomized GABABRKOs still have notable Kiss1 expression in the MeA, BnST, and LS, indicating that absent GABABR signaling upregulates Kiss1 in these regions even in the absence of sex steroids. In both genotypes, E2 further increases Kiss1 in the MeA, BnST, and LS, with higher levels in the GABABRKOs than WTs. Thus, E2 (stimulatory) and GABA (inhibitory) can independently regulate Kiss1 in extra-hypothalamic regions.Research Support: NSF IOS-1025893 and IOS-1457226 (ASK); P50 HD012303 (PLM/ASK); NIH T32 HD007203 (SBZS), NIH F32 HD088060 (SBZS), and NIH K99 HD092894 (SBZS); CONICET- ANPCYT-Fundación René Barón (VLL); ANPCYT-UBA (CL).Keywords: Kisspeptin, Amygdala, BnST, Septum, Estradiol, GABA