Alterations In The Regulation Of The GnRH-Gonadotrophic Axis In Neonatal GABAB1KO Mice.

NOELIA DI GIORGIO; PAOLO N. CATALANO; BERNHARD BETTLER; CARLOS LIBERTUN; VICTORIA LUX-LANTOS

Salzburgo

Congreso; The 10th International Symposium on GnRH.; 2011

Kenes International

Lack of functional GABAB receptors (GABAB1KO) alters the gonadotropic axis, including hypothalamic sexual dimorphic GnRH expression and GABA content in adult mice (Am.J.Physiol.Endocrinol.Metab.2010;298(3):E683-96). We studied 4-day-old (PND4) mice to determine whether sex and genotype differences have already occurred at this stage. Both sexes, wild-type (WT) and GABAB1KO mice were killed at PND4, their hypothalami (HT), frontopariental cortex (CT, control) and adenopituitaries obtained to study GnRH and gonadotropins content respectively (RIA) and GABA content (HPLC). We studied GnRH and GAD67 mRNA expression in anterior (AH) and medial-basal (MBH) hypothalamus and CT (qRT-PCR). Serum gonadotropins were measured (RIA). GnRH in HT was sexually dimorphic in WTs, male higher than female; this difference was inverted in GABAB1KO (p<0.01). In AH, GnRH and GAD67 mRNAs were similar among groups. In MBH, they were sexually dimorphic only in GABAB1KO (females higher than males, p<0.03 and p<0.02, respectively). GABA in HT was higher in male than in females (p<0.05), without genotype differences. No differences were observed in CT in any parameter. Pituitary LH increased in GABAB1KO in both sexes (p<0.02), FSH content was similar among groups. Serum LH increased only in GABAB1KO females (p<0.05), FSH was higher in females than in males (p<0.001).The absence of functional GABAB receptors alters the hypothalamic-pituitary axis already at PND4. GABAB1KO mice have alterations in hypothalamic GnRH, GnRH and GAD67 mRNAs in MBH and LH content and serum levels. However, these alterations differ from those observed in adulthood, suggesting additional regulations in later stages of development. (CONICET-ANPCYT-UBA)