Effects of dietary phytoestrogen exposure during perinatal period.

Developmental effects of phytoestrogens were studied in offspring from pregnant rats who received a free-feeding diet of either rat chow that was very low in phytoestrogens (low phyto), rat chow low in phytoestrogens and given a genistein and diadzein supplement tablet (high phyto), or normal rat chow (normal) from the second week of pregnancy to weaning (postnatal day 21). Measurements of anogenital distance, daily weights, righting reflex and ultrasonic vocalizations were made on neonatal pups and plasma testosterone and corticosterone were assessed in adult males. There was a significant effect of phytoestrogen treatment on USV for all male and female offspring. Differences between groups in daily weights and anogenital distance were attributed to the micronutrient levels of the two rat chow types employed in this study. No differences in righting reflex test, corticosterone levels or testosterone levels were found among treatment conditions. These results are the first demonstration of phytoestrogens affecting USVs and underscore the complexity of the effects of these substances on biobehavioral development.

Conversion of human-selective PPARalpha agonists to human/mouse dual agonists: a molecular modeling analysis.

To understand the species selectivity in a series of alpha-methyl-alpha-phenoxy carboxylic acid PPARalpha/gamma dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARalpha. This study suggested that interaction of both 4-phenoxy and phenyloxazole substituents of these ligands with F272 and M279 in mouse PPARalpha leads to the species-specific divergence in ligand binding. Insights obtained in the molecular modeling studies of these key interactions resulted in the ability to convert a human-selective PPARalpha agonist to a human and mouse dual agonist within the same platform.