Blocking GABAB receptors (GABABR) from birth to weaning in mice induces profound changes in the gonadotropic axis.

BIZZOZZERO MARIANNE; DI GIORGIO NOELIA P; LIBERTUN CARLOS; LUX LANTOS V

Congreso; XX Jornadas anuales de la Sociedad Argentina de Biologia y la XVII Jornada de la Sociedad Uruguaya de Biociencias.; 2018

BLOCKING GABAB RECEPTORS (GABABR) FROM BIRTH TO WEANING IN MICE INDUCES PROFOUND CHANGES IN THE GONADOTROPIC AXISBizzozzero Hiriart M, Di Giorgio NP, Libertun C and Lux-Lantos V. Instituto de Biología y Medicina Experimental (IBYME-CONICET, Buenos Aires, Argentina). m.bizzozzero@hotmail.comWe have previously shown that the administration of a GABAB antagonist (CGP55845) to neonatal BALB/C mice from postnatal day (PND) 2-6 significantly decreased arcuate nucleus (ARC) kisspeptin (Kiss1) expression in both sexes. Furthermore, CGP55845 decreased PND7 BW, increased PND7 and PND21 anogenital index (AGI) and delayed puberty onset in females. Here our aim was to induce a more sustained inhibition of GABABR signaling and evaluate its effects on the gonadotropic axis.Neonatal Balb/c male (M) and female (F) mice were injected with CGP55845 (1 mg/kg, sc, CGP) or saline (Sal) from PND2-21, three times/day (8AM, 1PM, 6PM) and 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 500 µm slices were obtained on a cryostat. ARC and antero ventral periventricular nucleus (AVPV) micropunches were obtained. Kiss1, kisspeptin receptor (Kiss1r), prodynorfin (Pdyn), neurokinin B (Tac2), tyrosine hydrolxylase (TH), progesterone receptor (Pgr), GABAB1 and GABAB2 subunits of the GABABR (GABAB1, GABAB2) mRNA expression was assessed in the micropunches by qPCR (control gene: Cyclophilin B). Body weight (BW) and AGI (anogenital distance/BW) were evaluated on PND 7, 14 and 21. In the ARC CGP induced a decrease in Kiss1 (FCTRL: 1,16±0.24 vs FCGP: 0,67±0.16 vs MCTRL: 1,22±0.24 vs MCGP: 0,70±0.13, CGP vs CTRL p