Steroids and endocrine disruptors—History, recent state of art and open questions. Issue 155 (January 2016)

• Record Type: Journal Article
• Authors: Hampl, Richard; Kubátová, Jana; Stárka, Luboslav
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 155 Part B(2016)
• Page Start: 217
• Page End: 223
• Publication Date: 2016-01
• Subjects: BPA bisphenol A -- DDE 2, 2′-bis-(4-chlorophenyl)-1, 1′-dichloroethene -- DDT dichlorodiphenyltrichloroethane -- FSH folitropin -- LH lutropin -- PCB(s) polychlorinated biphenyl(s) -- PFOA perfluorooctanoic acid -- PFOS perfluorooctanesulfonic acid -- SHBG sex hormone-binding globulin; Steroids -- Endocrine disruptors -- Sites of action -- Overreview; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2014.04.013
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Levels and sites at which endocrine disruptors affect steroid actions are overeviewed. Opened questions and perspectives are pointed out, especially. Effects of endocrine disruptors on hypothalamic–pituitary gonadal and adrenal axes. Effects of endocrine disruptors steroid binding to plasma proteins. Association of endocrine disruptor concentrations with steroid levels in body fluids. Abstract: This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3β-, 11β- and 17β-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo–pituitary–adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in mammals, and various EDs affect its expression and function. Finally, advances in analytics of EDs, especially those persisting in the environment, in various body fluids (plasma, urine, seminal fluid, and follicular fluid) are mentioned. Surprisingly, relatively scarce information is available on the simultaneous determination of EDs and steroids in the same biological material. This article is part of a Special Issue entitled 'Endocrine disruptors & steroids'.