Responses to kisspeptin are altered in hypothalamic explants of adult GABAB1KO mice.

DI GIORGIO N; CATALANO P; BETTLER B; LIBERTUN C; LUX-LANTOS V

Salzburgo

Simposio; 10th International Symposium on GnRH: hypothalamic-pituitary-gonadal axis in cancer and reproduction; 2011

Adult mice lacking a functional GABAB receptor (GABAB1KO) show an altered regulation of GnRH. Alterations include GnRH and GABA contents, GnRH pulsatility and GnRH and GAD67 mRNA expression in hypothalamus (HT) (Am.J.Physiol.Endocrinol.Metab.2010;298(3):E683-96). We studied the responses to Kisspeptin in GABAB1KO mice. We determined GnRH secretion (RIA) and expression (qRT-PCR) and GAD67 expression in hypothalamic explants of adult mice [both sexes, wild-type (WT) and GABAB1KO] which were incubated with Kiss-10 (1.10-8M) or buffer (control) for 150 min. Kiss-10 increased GnRH secretion in all groups (Three-way ANOVA, all interactions: ns; treatment: p<0.001). However, in the Kiss-10-stimulated group, GnRH secretion was lower in GABAB1KO compared to WT males (p<0.02), without genotype differences in females. GnRH expression was affected by sex, genotype and treatment (Three-way ANOVA, triple interaction: p<0.03). In basal conditions, GABAB1KO males had lower GnRH expression than GABAB1KO females (p<0.01) and WT males (p<0.05), without sexual differences in WTs. Kiss-10 increased GnRH expression only in GABAB1KO males (p<0.05), without differences between Kiss-10 groups. GAD67 expression was affected by sex, genotype and treatment (Three-way ANOVA, triple interaction: p<0.05). Basal GAD67 expression was higher in males than females (p<0.01) and higher in GABAB1KOs than WTs (p<0.01). GAD67 in Kiss-10 males was similar to basal males, keeping their genotype differences. GAD67 increased in Kiss-10 WT females compare to basal females (p<0.03), without differences in GABAB1KO females. Responses to Kisspeptin are altered in hypothalamic explants of adult GABAB1KO mice with sex-specific modifications. (CONICET-ANPCYT-UBA)