Sex differences in LXR expression in normal offspring and in rats born to diabetic dams.
Gestational diabetes (GD) alters normal fetal development and is related to a diabetogenic effect in the progeny. Liver X receptors (LXRs) are considered to be potential drug targets for the regulation, treatment, or prevention of diabetes. The aim of this study was to evaluate early and late changes of LXR in the hippocampus and hypothalamus of the male and female offspring of control (CO) and diabetic (DO) mothers. We used an experimental model of streptozotocin-induced GD to assess the protein expression of LXRα (NR1H3) and LXRβ (NR1H2) by western blotting. The tissues were obtained from CO and DO animals at postnatal day 1 (1D), day 10 (10D), and day 35 (35D) and 9 months (9M). In CO, the LXR expression showed significant differences among the groups, which were tissue- and receptor-specific (P<0.05). Sex differences in CO were found only in the hypothalamus for LXRβ expression at 35D and 9M (P<0.05). When CO and DO were compared, differences between them were observed in the majority of the studied groups at 1D (male hippocampus, LXRα 31% and LXRβ 161%; female hippocampus, LXRβ 165%; male hypothalamus, LXRβ 182%; and female hypothalamus, LXRα 85%; P<0.05). However, these differences disappeared later with the exception of LXRβ expression in the male hypothalamus (P<0.05). The area under the curve during the glucose tolerance test correlated negatively with LXRβ in CO but not in DO animals. Moreover, in a male DO subpopulation this correlation was positive as it occurs in intolerant animals. These results indicate that GD affects hypothalamic LXR expression differently in male and female offspring.
Laboratorio de NeurobiologíaInstituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, ArgentinaDepartamento de Bioquímica HumanaFacultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG Ciudad Autónoma de Buenos Aires, ArgentinaFacultad de Ciencias MedicasUniversidad Católica de Cuyo, Rivadavia, Provincia de San Juan, Argentina.
María Sol
MS
Kruse
Laboratorio de NeurobiologíaInstituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, ArgentinaDepartamento de Bioquímica HumanaFacultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG Ciudad Autónoma de Buenos Aires, ArgentinaFacultad de Ciencias MedicasUniversidad Católica de Cuyo, Rivadavia, Provincia de San Juan, Argentina.
María Cristina
MC
Vega
Laboratorio de NeurobiologíaInstituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, ArgentinaDepartamento de Bioquímica HumanaFacultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG Ciudad Autónoma de Buenos Aires, ArgentinaFacultad de Ciencias MedicasUniversidad Católica de Cuyo, Rivadavia, Provincia de San Juan, Argentina.
Mariana
M
Rey
Laboratorio de NeurobiologíaInstituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, ArgentinaDepartamento de Bioquímica HumanaFacultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG Ciudad Autónoma de Buenos Aires, ArgentinaFacultad de Ciencias MedicasUniversidad Católica de Cuyo, Rivadavia, Provincia de San Juan, ArgentinaLaboratorio de NeurobiologíaInstituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, ArgentinaDepartamento de Bioquímica HumanaFacultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG Ciudad Autónoma de Buenos Aires, ArgentinaFacultad de Ciencias MedicasUniversidad Católica de Cuyo, Rivadavia, Provincia de San Juan, ArgentinaLaboratorio de NeurobiologíaInstituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, ArgentinaDepartamento de Bioquímica HumanaFacultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 5to Piso, C1121ABG Ciudad Autónoma de Buenos Aires, ArgentinaFacultad de Ciencias MedicasUniversidad Católica de Cuyo, Rivadavia, Provincia de San Juan, Argentina hcoirini@ibyme.conicet.gov.ar.
Héctor
H
Coirini
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005951:Glucose Tolerance Test; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013311:Streptozocin / Q000009:adverse effects; D013997:Time Factors
D000071518:Liver X Receptors; C000605212:Nr1h2 protein, rat; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D013311:Streptozocin
AUC; gestational diabetes; glucose tolerance test; insulin resistance