[Effect of retinol on interaction of the protein period1, oxytocin, and GABA at the prenatal period of formation of the circadian clock-mechanism in rats]

Abstract

Clock-gene proteins are expressed in mammals in neurons of the hypothalamus suprachiasmatic nucleus and of other CNS structures, in muscles, viscercal organs, and vessels, and form circadian rhythms of many functions. Little is known about the factors of formation of the circadian mechanism at the prenatal period. In rats the E20 stage is characterized by a high level of oxytocin and selective expression of the first protein of the clock-genes PER1. The foal of the present study was to check the suggestion about the positive feedback between PER1 and oxytocin at the prenatal period as well as to elucidate a possible role of PER1 in regulation of interactions between oxytocin and GABA at the period of formation of the cerebral circadian mechanism of clock-genes. With aid of western-blotting, we analyzed the nuclear and cytoplasmic fractions from anterior hypothalamus homogenate in pregnant females and embryos of rats (E20). The retinol metabolites through their nuclear receptor RORalpha are known to be bound to promoters of genes of oxytocin and per 1. Next day after administration of retinol to the females, a rise of PER1 content was noted in their cytoplasm, whereas in their embryos the PER1 content was elevated in the nucleus. In the embryo cytoplasm there was a significant rise of production of oxytocin receptors and a decrease of the level of enzymes of GABA synthesis (glutamate decarboxylases 67 and 65). The results indicate the oxytocin- and retinol-dependent increase of the PER1 expression and the subsequent change of ratio of efficiency of oxytocin and GABA at the prenatal stage of formation of the circadian clock-mechanism of the rat embryo anterior hypothalamus.