Effects of a GABAB Antagonist on Brain Kiss1 Expression in Mice.

BIZZOZZERO, MARIANNE; BOURGUIGNON, NADIA SOLEDAD; DI GIORGIO, NOELIA; TABARES, FLORENCIA; LIBERTUN, CARLOS; LUX-LANTOS, VICTORIA ADELA

Congreso; The Endocrine Society´s; 2017

We have shown that in adult GABAB1KO mice Kiss1 mRNA expression was similar to wild types in hypothalamic nuclei [arcuate (ARC) and anteroventral periventricular nucleus (AVPV)] but Kiss1 expression was markedly increased in extra-hypothalamic areas such as medial amygdala (MeA), bed nucleus of the stria terminalis and lateral septum (1). In contrast in neonatal female GABAB1KO mice Kiss1 mRNA expression in ARC was significantly lower than in WT female neonates, abolishing the normal sex differences observed at this age (females > males) (2). To determine whether these characteristics were imprinted during development or could be mimicked in adulthood, we studied the effects of the administration of a GABAB antagonist, CGP55845, on brain Kiss1 expression in adult and neonatal mice.Adult male Balb/c mice were injected with CGP (1 mg/kg, sc,) or saline (Sal) as control for 5 days, three times/day (8AM, 1PM, 6PM). Neonatal Balb/c mice were injected with CGP (1 mg/kg, sc) or Sal from postnatal day 2 (PND2) to PND6±1, three times/day (8AM, 1PM, 6PM). Mice were sacrificed at 3PM (after two injections on the last day). Serum samples and gonads were collected for hormonal measurements by RIA. Brains were frozen and 400 µm slices for neonates and 500 µm slices for adults were obtained on a cryostat. Micropunches were obtained: adults: ARC and MeA; neonates: ARC and AVPV. Kiss1 mRNA expression was assessed in the micropunches by qPCR (control gene: Cyclophilin B). In neonate micropunches we also determined aromatase expression by qPCR.In adult males Kiss1 expression in ARC (AU: Sal 1.2±0.1; CGP 1.3 ±0.2, NS) and MeA (AU: Sal 1.2±0.2; CGP 1.1±0.1, NS) showed no differences due to treatment. CGP did not modify either serum LH, prolactin or testicular and serum testosterone (T) or testicular estradiol (E2). The administration of a GABAB antagonist during adulthood could not modulate Kiss1 expression. In contrast, CGP significantly decreased ARC Kiss1 expression in both sexes (AU: ♀-Sal: 4.7±1.7, ♀-CGP: 3.0±1.1, ♂-Sal: 1.1±0.2, ♂-CGP: 0.5±0.1; CGP≠SAL: p