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      Placental contribution to the endocrinology of gestation and parturition

      research-article
      1 , 4 , 2 , 3
      Animal Reproduction
      Colégio Brasileiro de Reprodução Animal
      gonadotrophins, placenta, placental lactogen, relaxin, steroids.

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          Abstract

          In addition to many other functions, the placenta is a source of a vast number of autocrine, paracrine and endocrine factors. However, the spectrum of placental regulatory factors, their concentrations, gestational profiles and roles may differ considerably even between phylogenetically closely related species. Depending on the species, placental regulatory factors of a broad range of molecule classes have been found including (glyco-)proteins, peptides, steroids and prostaglandins. Local placental regulatory factors are especially important for the dialogue between the fetal and the maternal compartment immediately at the feto-maternal borderline and for the control of growth, differentiation and functions of the placenta itself. Moreover, placental hormones in a proper sense may also have effects in more remote targets within the maternal compartment, serving functions such as pregnancy-specific adaptations of maternal circulation, provision of hemotrophe to the fetus or the development and function of the mammary gland. Functions of placental hormones in the fetus proper are less clear but may be especially important before the establishment of a functional fetal endocrine system and near term within the highly species-specific networks of signals preparing and initiating parturition. This review takes a comparative view on the situation in different domestic animals focusing on ruminants and on placental hormones occurring at significant concentrations in the maternal circulation.

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          Most cited references181

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          Androgen Receptor Structure, Function and Biology: From Bench to Bedside.

          The actions of androgens such as testosterone and dihydrotestosterone are mediated via the androgen receptor (AR), a ligand-dependent nuclear transcription factor and member of the steroid hormone nuclear receptor family. Given its widespread expression in many cells and tissues, the AR has a diverse range of biological actions including important roles in the development and maintenance of the reproductive, musculoskeletal, cardiovascular, immune, neural and haemopoietic systems. AR signalling may also be involved in the development of tumours in the prostate, bladder, liver, kidney and lung. Androgens can exert their actions via the AR in a DNA binding-dependent manner to regulate target gene transcription, or in a non-DNA binding-dependent manner to initiate rapid, cellular events such as the phosphorylation of 2(nd) messenger signalling cascades. More recently, ligand-independent actions of the AR have also been identified. Given the large volume of studies relating to androgens and the AR, this review is not intended as an extensive review of all studies investigating the AR, but rather as an overview of the structure, function, signalling pathways and biology of the AR as well as its important role in clinical medicine, with emphasis on recent developments in this field.
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            Relaxin family peptides and their receptors.

            There are seven relaxin family peptides that are all structurally related to insulin. Relaxin has many roles in female and male reproduction, as a neuropeptide in the central nervous system, as a vasodilator and cardiac stimulant in the cardiovascular system, and as an antifibrotic agent. Insulin-like peptide-3 (INSL3) has clearly defined specialist roles in male and female reproduction, relaxin-3 is primarily a neuropeptide involved in stress and metabolic control, and INSL5 is widely distributed particularly in the gastrointestinal tract. Although they are structurally related to insulin, the relaxin family peptides produce their physiological effects by activating a group of four G protein-coupled receptors (GPCRs), relaxin family peptide receptors 1-4 (RXFP1-4). Relaxin and INSL3 are the cognate ligands for RXFP1 and RXFP2, respectively, that are leucine-rich repeat containing GPCRs. RXFP1 activates a wide spectrum of signaling pathways to generate second messengers that include cAMP and nitric oxide, whereas RXFP2 activates a subset of these pathways. Relaxin-3 and INSL5 are the cognate ligands for RXFP3 and RXFP4 that are closely related to small peptide receptors that when activated inhibit cAMP production and activate MAP kinases. Although there are still many unanswered questions regarding the mode of action of relaxin family peptides, it is clear that they have important physiological roles that could be exploited for therapeutic benefit.
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              The Regulation of Steroid Action by Sulfation and Desulfation

              Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined.
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                Author and article information

                Journal
                Anim Reprod
                Anim Reprod
                ar
                Animal Reproduction
                Colégio Brasileiro de Reprodução Animal
                1806-9614
                1984-3143
                03 August 2018
                Jul-Sep 2018
                : 15
                : Suppl 1
                : 822-842
                Affiliations
                [1 ] originalVeterinary Clinic for Obstetrics, Gynecology and Andrology, Faculty of Veterinary Medicine, Justus Liebig University, Giessen, Germany
                [2 ] originalLeibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
                [3 ] originalInstitute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
                Author notes
                [4 ] Corresponding author: gerhard.schuler@ 123456vetmed.uni-giessen.de Phone: +49(0641)99-38718; Fax: +49(0641)99-38709
                Article
                10.21451/1984-3143-AR2018-0015
                9536075
                36249837
                8deffa16-32e7-4059-afc7-e062885873b3

                Copyright © The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 January 2018
                : 18 May 2018
                Categories
                Article

                gonadotrophins,placenta,placental lactogen,relaxin,steroids.

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