Fetal liver may reinstate activity of GABAergic steroids inactivated by placental oxidoreductases
R. Kanceva1, M. Hill1, A. Parizek2, L. Kancheva1 & L. Starka1
Recently we have completed steroid metabolomic study including unconjugated (n=39) and conjugated steroids (n=30) in maternal and fetal body fluids using GC-MS method with two separate multicomponent analyses (for unconjugated steroids and steroid polar conjugates). Our previous data indicate that primarily oxidative isoforms of pluripotent 17β-hydroxysteroid dehydrogenases and aldoketoreductases in placental tissue close to the fetal compartment convert 3α-,17β- and 20α-hydroxy-groups in progestogens, estrogens and GABAergic steroids to the corresponding ketones. Therefore, GABAergic steroids are mostly inactivated when entering the fetus, which may negatively influence neuroprotective potential of these substances in the fetal brain. In this study we investigated the role of fetal liver in the reinstatement of the steroid GABAergic activity. The trial was approved by the Ethics Committee of the Institute of Endocrinology of Endocrinology, Prague, Czech Republic. In the study participated twelve women giving uncomplicated birth after the 38th week of gestation and 38 women with preterm labors (28th37th week) who were selected to provide maximum conformity of the steroid metabolome with the actual GA. The umbilical arteriovenous differences evaluated by Wilcoxons robust paired test as well as by multivariate statistics indicated that the activity of GABAergic steroids inactivated by placental oxidoreductases may be reinstated by liver enzymes, most probably from the aldoketoreductase family.
Grants IGA NT/11513 and NT/12211 and the advanced education of own staff in clinical and molecular endocrinology (CZ.2.17/1.1.00/32386) supported the study.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.