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In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological...
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In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 20675

Special Issue Editors

Prof. Dr. Thierry Charlier

E-Mail Website
Guest Editor
Research Institute for Health, Environmental and Occupational Health (IRSET), U1085 Inserm, TREC Team, University of Rennes, 35000 Rennes, France
Interests: behavioral neuroendocrinology; aromatase; hypothalamus; estrogens; androgens; endocrine disrupters
Special Issues, Collections and Topics in MDPI journals
Prof. Cathy Vaillancourt

E-Mail Website
Guest Editor
Centre Armand Frappier Santé Biotechnologie, Laval, QC H7V1B7, Canada
Interests: placenta; neuroendocrinology; gestation; neurotransmitters; hormones; stress; edocrine disrupters
Special Issues, Collections and Topics in MDPI journals
Dr. Devaleena S. Pradhan

E-Mail Website
Guest Editor
Department of Biological Sciences, Idaho State University, Pocatello, ID, USA
Interests: behavioral neuroendocrinology; steroidogenic enzymes; stress; hormone receptor; environmental physiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are delighted to announce a call for submissions to a Special Issue of the International Journal of Molecular Sciences on “In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions”. The current understanding of the mechanisms regulating steroid synthesis and metabolism goes far beyond the classical slow transcriptional processes occurring in a single defined gland. In addition to being steroid-targets, numerous tissues in various organs also participate in local steroidogenesis and steroid metabolism, and these modulations can occur rapidly, notably via post-translational modifications of steroidogenic enzymes. The scope of this Special Issue is to bring together research papers, targeted reviews, opinions, and perspectives that will lay out the latest understanding and pending questions regarding the mechanisms of steroid synthesis and metabolism in vivo. Amongst the various topics to be addressed are regulatory processes of steroid synthesis and metabolism by non-classical tissues, the rapid modulation of enzymatic activity, and the consequence of environmental and therapeutic exposure. In addition, we encourage submissions discussing these regulatory processes in light of changes during life span, physiological and pathological conditions, as well as sex differences.

Prof. Cathy Vaillancourt
Prof. Thierry Charlier
Dr. Devaleena S. Pradhan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Sex dimorphism 
  • Hormone 
  • Endocrine disruptor 
  • Receptors 
  • Local synthesis 
  • Steroid signaling

Related Special Issue

Published Papers (5 papers)

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Research

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24 pages, 5982 KiB  
Article
Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells
by Sathvika Venugopal, Melanie Galano, Rachel Chan, Esha Sanyal, Leeyah Issop, Sunghoon Lee, Lorne Taylor, Pushwinder Kaur, Edward Daly and Vassilios Papadopoulos
Int. J. Mol. Sci. 2021, 22(5), 2554; https://doi.org/10.3390/ijms22052554 - 04 Mar 2021
Cited by 6 | Viewed by 2325
Abstract
Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations [...] Read more.
Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations between the plasma membrane (PM) and the endoplasmic reticulum (ER) and between the ER and mitochondria. cAMP stimulation also increased the movement of cholesterol from the PM compared to untreated cells, which was partially inhibited when ATPase family AAA-domain containing protein 3 A (ATAD3A), which functions in ER and mitochondria interactions, was knocked down. Mitochondria, ER, cytoplasm, PM, PM-associated membranes (PAMs), and mitochondria-associated membranes (MAMs) were isolated from control and hormone-stimulated cells. Lipidomic analyses revealed that each isolated compartment had a unique lipid composition, and the induction of steroidogenesis caused the significant remodeling of its lipidome. cAMP-induced changes in lipid composition included an increase in phosphatidylserine and cardiolipin levels in PAM and PM compartments, respectively; an increase in phosphatidylinositol in the ER, mitochondria, and MAMs; and a reorganization of phosphatidic acid, cholesterol ester, ceramide, and phosphatidylethanolamine. Abundant lipids, such as phosphatidylcholine, were not affected by hormone treatment. Our data suggested that PM–ER–mitochondria tethering may be involved in lipid trafficking between organelles and indicated that hormone-induced acute steroid production involves extensive organelle remodeling. Full article
(This article belongs to the Special Issue In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions)
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17 pages, 3154 KiB  
Article
Role of Constitutive STAR in Leydig Cells
by Melanie Galano, Yuchang Li, Lu Li, Chantal Sottas and Vassilios Papadopoulos
Int. J. Mol. Sci. 2021, 22(4), 2021; https://doi.org/10.3390/ijms22042021 - 18 Feb 2021
Cited by 36 | Viewed by 2985
Abstract
Leydig cells contain significant amounts of constitutively produced steroidogenic acute regulatory protein (STAR; STARD1). Hormone-induced STAR plays an essential role in inducing the transfer of cholesterol into the mitochondria for hormone-dependent steroidogenesis. STAR acts at the outer mitochondrial membrane, where it interacts with [...] Read more.
Leydig cells contain significant amounts of constitutively produced steroidogenic acute regulatory protein (STAR; STARD1). Hormone-induced STAR plays an essential role in inducing the transfer of cholesterol into the mitochondria for hormone-dependent steroidogenesis. STAR acts at the outer mitochondrial membrane, where it interacts with a protein complex, which includes the translocator protein (TSPO). Mutations in STAR cause lipoid congenital adrenal hyperplasia (lipoid CAH), a disorder characterized by severe defects in adrenal and gonadal steroid production; in Leydig cells, the defects are seen mainly after the onset of hormone-dependent androgen formation. The function of constitutive STAR in Leydig cells is unknown. We generated STAR knockout (KO) MA-10 mouse tumor Leydig cells and showed that STAR KO cells failed to form progesterone in response to dibutyryl-cAMP and to TSPO drug ligands, but not to 22(R)-hydroxycholesterol, which is a membrane-permeable intermediate of the CYP11A1 reaction. Electron microscopy of STAR KO cells revealed that the number and size of lipid droplets were similar to those in wild-type (WT) MA-10 cells. However, the density of lipid droplets in STAR KO cells was drastically different than that seen in WT cells. We isolated the lipid droplets and analyzed their content by liquid chromatography–mass spectrometry. There was a significant increase in cholesteryl ester and phosphatidylcholine content in STAR KO cell lipid droplets, but the most abundant increase was in the amount of diacylglycerol (DAG); DAG 38:1 was the predominantly affected species. Lastly, we identified genes involved in DAG signaling and lipid metabolism which were differentially expressed between WT MA-10 and STAR KO cells. These results suggest that constitutive STAR in Leydig cells is involved in DAG accumulation in lipid droplets, in addition to cholesterol transport. The former event may affect cell functions mediated by DAG signaling. Full article
(This article belongs to the Special Issue In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions)
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16 pages, 1883 KiB  
Article
Revisiting Steroidogenic Pathways in the Human Placenta and Primary Human Trophoblast Cells
by Rona Karahoda, Sampada Kallol, Michael Groessl, Edgar Ontsouka, Pascale Anderle, Christa Fluck, Frantisek Staud and Christiane Albrecht
Int. J. Mol. Sci. 2021, 22(4), 1704; https://doi.org/10.3390/ijms22041704 - 08 Feb 2021
Cited by 24 | Viewed by 3816
Abstract
Steroid hormones play a crucial role in supporting a successful pregnancy and ensuring proper fetal development. The placenta is one of the principal tissues in steroid production and metabolism, expressing a vast range of steroidogenic enzymes. Nevertheless, a comprehensive characterization of steroidogenic pathways [...] Read more.
Steroid hormones play a crucial role in supporting a successful pregnancy and ensuring proper fetal development. The placenta is one of the principal tissues in steroid production and metabolism, expressing a vast range of steroidogenic enzymes. Nevertheless, a comprehensive characterization of steroidogenic pathways in the human placenta and potential developmental changes occurring during gestation are poorly understood. Furthermore, the specific contribution of trophoblast cells in steroid release is largely unknown. Thus, this study aimed to (i) identify gestational age-dependent changes in the gene expression of key steroidogenic enzymes and (ii) explore the role of trophoblast cells in steroid biosynthesis and metabolism. Quantitative and Droplet Digital PCR analysis of 12 selected enzymes was carried out in the first trimester (n = 13) and term (n = 20) human placentas. Primary trophoblast cells (n = 5) isolated from human term placentas and choriocarcinoma-derived cell lines (BeWo, BeWo b30 clone, and JEG-3) were further screened for gene expression of enzymes involved in placental synthesis/metabolism of steroids. Finally, de novo steroid synthesis by primary human trophoblasts was evaluated, highlighting the functional activity of steroidogenic enzymes in these cells. Collectively, we provide insights into the expression patterns of steroidogenic enzymes as a function of gestational age and delineate the cellular origin of steroidogenesis in the human placenta. Full article
(This article belongs to the Special Issue In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions)
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Review

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33 pages, 3415 KiB  
Review
Six Decades of Research on Human Fetal Gonadal Steroids
by Stéphane Connan-Perrot, Thibaut Léger, Pauline Lelandais, Christèle Desdoits-Lethimonier, Arthur David, Paul A. Fowler and Séverine Mazaud-Guittot
Int. J. Mol. Sci. 2021, 22(13), 6681; https://doi.org/10.3390/ijms22136681 - 22 Jun 2021
Cited by 15 | Viewed by 7084
Abstract
Human fetal gonads acquire endocrine steroidogenic capabilities early during their differentiation. Genetic studies show that this endocrine function plays a central role in the sexually dimorphic development of the external genitalia during fetal development. When this endocrine function is dysregulated, congenital malformations and [...] Read more.
Human fetal gonads acquire endocrine steroidogenic capabilities early during their differentiation. Genetic studies show that this endocrine function plays a central role in the sexually dimorphic development of the external genitalia during fetal development. When this endocrine function is dysregulated, congenital malformations and pathologies are the result. In this review, we explain how the current knowledge of steroidogenesis in human fetal gonads has benefited from both the technological advances in steroid measurements and the assembly of detailed knowledge of steroidogenesis machinery and its expression in human fetal gonads. We summarise how the conversion of radiolabelled steroid precursors, antibody-based assays, mass spectrometry, ultrastructural studies, and the in situ labelling of proteins and mRNA have all provided complementary information. In this review, our discussion goes beyond the debate on recommendations concerning the best choice between the different available technologies, and their degrees of reproducibility and sensitivity. The available technologies and techniques can be used for different purposes and, as long as all quality controls are rigorously employed, the question is how to maximise the generation of robust, reproducible data on steroid hormones and their crucial roles in human fetal development and subsequent functions. Full article
(This article belongs to the Special Issue In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions)
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13 pages, 897 KiB  
Review
The Enigma of the Adrenarche: Identifying the Early Life Mechanisms and Possible Role in Postnatal Brain Development
by Angela L. Cumberland, Jonathan J. Hirst, Emilio Badoer, Stefan A. Wudy, Ronda F. Greaves, Margaret Zacharin and David W. Walker
Int. J. Mol. Sci. 2021, 22(9), 4296; https://doi.org/10.3390/ijms22094296 - 21 Apr 2021
Cited by 10 | Viewed by 3591
Abstract
Dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) are dynamically regulated before birth and the onset of puberty. Yet, the origins and purpose of increasing DHEA[S] in postnatal development remain elusive. Here, we draw attention to this pre-pubertal surge from the adrenal gland—the adrenarche—and [...] Read more.
Dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) are dynamically regulated before birth and the onset of puberty. Yet, the origins and purpose of increasing DHEA[S] in postnatal development remain elusive. Here, we draw attention to this pre-pubertal surge from the adrenal gland—the adrenarche—and discuss whether this is the result of intra-adrenal gene expression specifically affecting the zona reticularis (ZR), if the ZR is influenced by the hypothalamic-pituitary axis, and the possible role of spino-sympathetic innervation in prompting increased ZR activity. We also discuss whether neural DHEA[S] synthesis is coordinately regulated with the developing adrenal gland. We propose that DHEA[S] is crucial in the brain maturation of humans prior to and during puberty, and suggest that the function of the adrenarche is to modulate, adapt and rewire the pre-adolescent brain for new and ever-changing social challenges. The etiology of DHEA[S] synthesis, neurodevelopment and recently described 11-keto and 11-oxygenated androgens are difficult to investigate in humans owing to: (i) ethical restrictions on mechanistic studies, (ii) the inability to predict which individuals will develop specific mental characteristics, and (iii) the difficulty of conducting retrospective studies based on perinatal complications. We discuss new opportunities for animal studies to overcome these important issues. Full article
(This article belongs to the Special Issue In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions)
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