Multiple failures in the LH surge generating system in GABA1KO female mice.

BERNHARD BETTLER; NOELIA DI GIORGIO; CARLOS LIBERTUN; MARIANNE BIZZOZZERO HIRIART; VICTORIA LUX LANTOS; NADIA S BOURGUIGNON

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. 13 a 17 de noviembre 2017.; 2017

Sociedades Argentinas de Biociencias

Kisspeptin and GABA regulate reproduction. Global GABAB1KO(KO) females show impaired ovulation and reproduction, alteredcyclicity and GnRH physiology. However Kiss1 mRNA in AVPV orARC was unaltered, suggesting that its expression at the mRNAlevel was not involved. Here we aimed to unravel the origin/s of thereproductive impairment in GABAB1KO female mice. Adult WT/KOfemales were ovariectomized (OVX), treated with E2 valerate (VAL,10ug/kg) and sacrificed 7 days post-OVX. Serum LH and E2 weredetermined (RIA). We evaluated GnRH response to one pulse ofKiss-10 /hour (10-7M) and/or constant E2 (10-8M) in ex vivo incubatedhypothalami (HT). Medium GnRH levels were measured (RIA).Anterior and medial basal HT from another set of WT/KO OVX-VALfemales were dissected to determine estrogen (Esr1 and Esr2) andkisspeptin (Kiss1r) receptors expression (qPCR). Other OVX WT/KO females were given sc E2 implants, which produce an LH surge2 days later around lights off. They were anesthetized at 10AM or6:30PM, blood collected to determine LH and PFA perfused. Brainswere kept for double IHQ assays (c-Fos/Kisspeptin). OVX+VAL hadlower LH compared to OVX and higher E2 than estrous females.GnRH pulse frequency was increased by E2+Kiss-10 in WT HT.Conversely, in KO HT, E2 increased GnRH pulse frequency and thiswas reversed by E2+Kiss-10 (pulses/h: WT:7.6±0.2 vs KO:5.0±0.3,p