Impaired GABAB receptor signaling dramatically up-regulates Kiss1 expression selectively in nonhypothalamic brain regions of adult but not prepubertal mice
| Autor: | Carlos Libertun, Joshua Kim, Sheila J. Semaan, Paula V. López, Noelia Paula Di Giorgio, Alexander S. Kauffman, Bernhard Bettler, Victoria Lux-Lantos |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Time Factors Medical and Health Sciences Mice Endocrinology Kisspeptin Receptors Testosterone BRAIN gamma-Aminobutyric Acid Mice Knockout Neurons Brain Mapping Kisspeptins Estradiol Septal nuclei purl.org/becyt/ford/3.1 [https] Bioquímica y Biología Molecular Biological Sciences Amygdala Immunohistochemistry Up-Regulation Medicina Básica medicine.anatomical_structure Phenotype Hypothalamus SIGNALING Neurological purl.org/becyt/ford/3 [https] Female medicine.drug Signal Transduction medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD Genotype Knockout 1.1 Normal biological development and functioning Midline Thalamic Nuclei In situ hybridization Biology GABAB receptor gamma-Aminobutyric acid Endocrinology & Metabolism Underpinning research Internal medicine GABAB medicine Animals Agricultural and Veterinary Sciences GABA-B Contraception/Reproduction Arcuate Nucleus of Hypothalamus Neurosciences Neuroendocrinology Stria terminalis nervous system Receptors GABA-B Gene Expression Regulation Septal Nuclei KISS1 |
| Zdroj: | Endocrinology, vol 155, iss 3 Endocrinology CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | Kisspeptin, encoded by Kiss1, stimulates reproduction and is synthesized in the hypothalamic anteroventral periventricular and arcuate nuclei. Kiss1 is also expressed at lower levels in the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST), but the regulation and function of Kiss1 there is poorly understood. γ-Aminobutyric acid (GABA) also regulates reproduction, and female GABAB1 receptor knockout (KO) mice have compromised fertility. However, the interaction between GABAB receptors and Kiss1 neurons is unknown. Here, using double-label in situ hybridization, we first demonstrated that a majority of hypothalamic Kiss1 neurons coexpress GABAB1 subunit, a finding also confirmed for most MeA Kiss1 neurons. Yet, despite known reproductive impairments in GABAB1KO mice, Kiss1 expression in the anteroventral periventricular and arcuate nuclei, assessed by both in situ hybridization and real-time PCR, was identical between adult wild-type and GABAB1KO mice. Surprisingly, however, Kiss1 levels in the BNST and MeA, as well as the lateral septum (a region normally lacking Kiss1 expression), were dramatically increased in both GABAB1KO males and females. The increased Kiss1 levels in extrahypothalamic regions were not caused by elevated sex steroids (which can increase Kiss1 expression), because circulating estradiol and testosterone were equivalent between genotypes. Interestingly, increased Kiss1 expression was not detected in the MeA or BNST in prepubertal KO mice of either sex, indicating that the enhancements in extrahypothalamic Kiss1 levels initiate during/after puberty. These findings suggest that GABAB signaling may normally directly or indirectly inhibit Kiss1 expression, particularly in the BNST and MeA, and highlight the importance of studying kisspeptin populations outside the hypothalamus. Fil: Di Giorgio, Noelia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Semaan, Sheila J.. University of California at San Diego; Estados Unidos Fil: Kim, Joshua. University of California at San Diego; Estados Unidos Fil: Lopez, Paula Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Bettler, Bernhard. Universidad de Basilea; Suiza Fil: Libertun, Carlos. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Kauffman, Alexander S.. University of California at San Diego; Estados Unidos |
| Databáze: | OpenAIRE |
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