Sexual differences on LXR expression in the hypothalamus of normal offspring and rats born from diabetic dams

KRUSE, M. S.; VEGA, M.C.; REY, M.; COIRINI, H

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2014 vol. 222 p. 53 - 60

0022-0795

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 LXRa (NR1H3) and LXRb (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 LXRb 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, LXRa 31% and LXRb 161%; female hippocampus, LXRb 165%; male hypothalamus, LXRb 182%; and female hypothalamus, LXRa 85%; P!0.05). However, these differences disappeared later with the exception of LXRb expression in the male hypothalamus (P!0.05). The area under the curve during the glucose tolerance test correlated negatively with LXRb 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.