Meeting Abstract

P1.127  Monday, Jan. 4  Progesterone metabolites, “xenobiotic-sensing” nuclear receptors, and the metabolism of maternal steroids PAITZ, RT*; BOWDEN, RM; Illinois State University; Illinois State University rpaitz@ilstu.edu

During development, embryos utilize steroid signals to direct sexual differentiation of tissues necessary for reproduction. Modulation of these signals by exogenous substances (both natural and synthetic) frequently produces phenotypic effects that can persist into adulthood and influence reproduction. In both oviparous and viviparous amniotes, embryos may be exposed to active steroid signals from the maternal environment. Understanding how embryos process maternal steroids is important to deciphering the evolutionary consequences of these steroid signals. Here we present evidence that during embryonic development, progesterone metabolites and xenobiotic-sensing nuclear receptors may interact to increase the expression of numerous enzymes responsible for steroid metabolism and illustrate how such a system can operate in both oviparous and placental amniotes. In these groups, embryonic development is characterized by 1) elevated progesterone concentrations, 2) 5β reduction being the primary metabolic pathway of progesterone, 3) the presence of xenobiotic-sensing nuclear receptors that can bind 5β metabolites of progesterone, and 4) increased expression of a suite of enzymes responsible for the metabolism of multiple steroids. We propose that xenobiotic-sensing nuclear receptors initially evolved to buffer the developing embryo from the potentially adverse effects of various maternal steroids on sexual differentiation.