title: Steroid metabolome in fetal and maternal body fluids in human late pregnancy.
abstract: Despite the extensive research during the last six decades the fundamental questions concerning the role of steroids in the initiation of human parturition and origin and function of some steroids in pregnancy were not definitely answered. Based on steroid metabolomic data found in the literature and our so far unpublished results, we attempted to bring new insights concerning the role of steroids in the sustaining and termination of human pregnancy, and predictive value of these substances for estimation of term. We also aimed to explain enigmas concerning the biosynthesis of progesterone and its bioactive catabolites considering the conjunctions between placental production of CRH, synthesis of bioactive steroids produced by fetal adrenal, localization of placental oxidoreductases and sustaining of human pregnancy. Evaluation of data available in the literature, including our recent findings as well as our new unpublished data indicates increasing progesterone synthesis and its concurrently increasing catabolism with approaching parturition, confirms declining production of pregnancy sustaining 5β-pregnane steroids providing uterine quiescence in late pregnancy, increased sulfation of further neuroinhibiting and pregnancy sustaining steroids. In contrast to the established concept considering LDL cholesterol as the primary substrate for progesterone synthesis in pregnancy, our data demonstrates the functioning of alternative mechanism for progesterone synthesis, which is based on the utilization of fetal pregnenolone sulfate for progesterone production in placenta. Close relationships were found between localization of placental oxidoreductases and consistently higher levels of sex hormones, neuroactive steroids and their metabolites in the oxidized form in the fetus and in the reduced form in the maternal compartment.
authors.affiliation: Institute of Endocrinology, Národní třída 8, Prague CZ 116 94, Czech Republic. mhill@endo.cz
authors.forename: Martin
authors.initials: M
authors.lastname: Hill
authors.forename: Antonín
authors.initials: A
authors.lastname: Pařízek
authors.forename: David
authors.initials: D
authors.lastname: Cibula
authors.forename: Radmila
authors.initials: R
authors.lastname: Kancheva
authors.forename: Jan Evangelista
authors.initials: JE
authors.lastname: Jirásek
authors.forename: Marie
authors.initials: M
authors.lastname: Jirkovská
authors.forename: Marta
authors.initials: M
authors.lastname: Velíková
authors.forename: Jana
authors.initials: J
authors.lastname: Kubátová
authors.forename: Michaela
authors.initials: M
authors.lastname: Klímková
authors.forename: Andrea
authors.initials: A
authors.lastname: Pašková
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Zižka
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Kancheva
authors.forename: Hana
authors.initials: H
authors.lastname: Kazihnitková
authors.forename: Ludmila
authors.initials: L
authors.lastname: Zamrazilová
authors.forename: Luboslav
authors.initials: L
authors.lastname: Stárka
mesh_terms: D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism*
chemical_list: D013256:Steroids