Estradiol-dependent and -independent stimulation of KIss1 expression in the amygdala, BNST, and lateral septum of mice

• Autores: Stephens, Shannon B.Z.; Di Giorgio, Noelia Paula; Liaw, Reanna B.; Parra, Ruby A.; Yang, Jennifer A.; Chahal, Navdeep; Lux, Victoria Adela R.; Kauffman, Alexander S.
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: KISSPEPTIN; KISS1; AMYGDALA; BNST; LATERAL SEPTUM; ESTRADIOL; GABA; GABAB RECEPTOR
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Kisspeptin, encoded by Kiss1, activates reproduction by stimulating GnRH neurons. Although most Kiss1 neurons are located in the hypothalamus, smaller Kiss1 populations also reside in the medial amygdala (MeA), bed nucleus of the stria terminalis (BnST), and lateral septum (LS). However, very little is known about the regulation and function of these extra-hypothalamic Kiss1 neurons. This study focused on the roles and interactions of two signaling factors, estradiol (E 2 ) and GABA, known to stimulate and inhibit, respectively, extra-hypothalamic Kiss1 expression. First, using estrogen receptor (ER)a knockout (KO) and bERKO mice, we demonstrated that Kiss1 in both the BnST and LS is stimulated by E 2 , as occurs in the MeA, and that this E 2 upregulation occurs via ERa, but not ERb. Second, using GABA B R KO and wild-type mice, we determined that whereas E 2 normally increases extra-hypothalamic Kiss1 levels, such upregulation by E 2 is further enhanced by the concurrent absence of GABA B R signaling in the MeA and LS, but not the BnST. Third, we demonstrated that when GABA B R signaling is absent, the additional removal of gonadal sex steroids does not abolish Kiss1 expression in the MeA and BnST, and in some cases the LS. Thus, Kiss1 expression in these extra-hypothalamic regions is not solely dependent on E 2 stimulation. Finally, we demonstrated a significant positive correlation between Kiss1 levels in the MeA, BnST, and LS, but not between these regions and the hypothalamus (anteroventral periventricular nucleus/periventricular nucleus). Collectively, our findings indicate that both E 2 and GABA independently regulate all three extra-hypothalamic Kiss1 populations, but their regulatory interactions may vary by brain region and additional yet-to-be-identified factors are likely involved.
Fil: Stephens, Shannon B.Z.. University of California at San Diego; Estados Unidos
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: Liaw, Reanna B.. University of California at San Diego; Estados Unidos
Fil: Parra, Ruby A.. University of California at San Diego; Estados Unidos
Fil: Yang, Jennifer A.. University of California at San Diego; Estados Unidos
Fil: Chahal, Navdeep. University of California at San Diego; Estados Unidos
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