Dramatic enhancement of Kiss1 expression in select brain regions of GABAB1 receptor knockout mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 112-141-Hypothalamus-Pituitary Development & Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-127
Noelia Paula Di Giorgio1, Sheila J Semaan2, Bernhard Bettler3, Victoria Adela Lux-Lantos1 and Alexander S Kauffman*2
1IBYME, Buenos Aires, Argentina, 2University of California San Diego, La Jolla, CA, 3Univ. of Basel, Basel, Switzerland
Kisspeptin, a neuropeptide encoded by the Kiss1 gene, stimulates GnRH neurons and is synthesized in the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei of the hypothalamus. Kiss1 is also expressed to a lesser extent in the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST), but the regulation and function of Kiss1 in these regions is poorly understood. The neurotransmitter GABA, acting through GABAA and GABAB receptors (GABABRs), also regulates reproduction. Adult female GABAB1R knockout (GABAB1RKO) mice have altered GnRH pulsatility and GnRH levels, as well as compromised fertility. However, the interaction between GABABRs and Kiss1 neurons is unknown. To test whether reproductive impairments in GABAB1RKOs reflect changes in kisspeptin, we first used double-label in situ hybridization (ISH) to assess GABAB1R co-localization in Kiss1 neurons. We found that virtually all Kiss1 neurons (~98%) co-express GABAB1R. We next studied Kiss1 mRNA levels in the AVPV and ARC of adult wild-type (WT) and GABAB1RKO mice of both sexes. Despite known reproductive impairments in GABAB1RKO mice, Kiss1 expression, assessed by both ISH and real-time PCR, was identical between genotypes in the AVPV and ARC. Next, we analyzed Kiss1 levels in the BNST, MeA, and septum using ISH. Surprisingly, Kiss1 levels were dramatically elevated in all 3 regions in GABAB1RKO mice of both sexes. This result was confirmed with real-time PCR on micropunches from specific areas. Since circulating sex steroids can strongly alter Kiss1 expression, we measured serum estradiol and testosterone levels in adult mice of both genotypes. Interestingly, circulating sex steroid levels were equivalent between genotypes, suggesting alternate reasons for the extremely high Kiss1 expression in extra-hypothalamic regions. Current experiments are determining the developmental ontogeny of these intriguing Kiss1 alterations. Collectively, our novel findings indicate that GABAB1RKO mice have dramatic alterations in the neural Kiss1 system, particularly in the BNST and MeA, and highlight the importance of studying other kisspeptin populations outside of the hypothalamus.

Nothing to Disclose: NPD, SJS, BB, VAL, ASK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm