IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
147. Infertility in GABAB1KO Female Mice: Possible Role of Brain Estrogens and Hypothalamic Response to Kisspeptin.
Autor/es:
DI GIORGIO N; LOPEZ P; BOURGUIGNON N.; SEEMAN SHEILA; BETTLER, B.; KAUFFMAN AS; LIBERTUN C; LUX LANTOS V
Reunión:
Congreso; ICE/ENDO 2014; 2014
Resumen:
Infertility in GABAB1KO female mice: possible role of brain estrogens and hypothalamic response to kisspeptin. Noelia P Di Giorgio1, Paula V López1, Nadia S Bourguignon1, Sheila J Semaan2, Bernhard Bettler3, Alexander S Kauffman2, Carlos Libertun1-4 and Victoria A Lux-Lantos1. 1. Institute of Biology and Experimental Medicine¬-CONICET, Buenos Aires, Argentina. 2. Dept of Reproductive Medicine, U.C. San Diego, La Jolla, CA, USA. 3. Dept of Biomedicine, Univ. of Basel, Basel, Switzerland. 4. Dept of Physiology, Univ. of Buenos Aires, Buenos Aires, Argentina. Adult GABAB1KO (KO) female mice, which lack functional GABAB receptors, have altered cyclicity, increased GnRH pulsatility and infertility. Moreover, Gnrh1 and Gad1 (enzyme that synthesizes GABA) mRNA expressions are altered in KO hypothalami (H), especially in anterior H (AH) and this is not due to serum estrogen levels. We also showed that Kiss1 mRNA in anteroventral/periventricular (AVPV/PeN) and arcuate (ARC) nuclei is similar to adult WT females (AJP-EM 2010:298:E683, Di Giorgio et al, Endocrinology 2014 Epub). Here we evaluated the role of brain estrogens in these effects, in WT and KO adult female mice (in estrus) and, comparatively, in males. We also evaluated GnRH pulsatility in the presence of Kiss1r agonist and/or antagonist in E2-treated ovariectomized adult mice. We determined aromatase (Cyp19a1) and alpha estrogen receptor (Er1) mRNA expressions in AH and medial basal H (MBH) and progesterone receptor (Pgr) mRNA expression in micropunches of AVPV/PeN and ARC by qPCR in WT and KO mice. For in vitro GnRH pulsatility studies, adult WT and KO females were ovariectomized and treated immediately with a single dose of estradiol valerate (sc, 10µg/kg). Seven days post-ovariectomy, they were sacrificed. H were collected and incubated in 250 µl of Krebs-Ringer bicarbonate buffer-4.5 mg/ml glucose-16 mM HEPES at 37°C for 7.5h. Treatments: control (CT), Kiss-10 (agonist, 1.10-7M), Kiss-234 (antagonist, 1.10-7M) and Kiss-10+Kiss-234 (1.10-7M each). Media were collected at 9-min intervals and replaced with fresh medium with/without stimuli. Secreted GnRH was measured by RIA. Cyp19a1 was higher in males vs females (p