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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. Dr. Thierry Charlier
Dr. Devaleena S. Pradhan
Dr. Cathy Vaillancourt
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.

Related Special Issue

Published Papers (2 papers)

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Research

25 pages, 3172 KiB

Open AccessArticle

Mechanism of Action of an Environmentally Relevant Organochlorine Mixture in Repressing Steroid Hormone Biosynthesis in Leydig Cells

by Annick N. Enangue Njembele, Zoheir B. Demmouche, Janice L. Bailey and Jacques J. Tremblay

Int. J. Mol. Sci. 2022, 23(7), 3997; https://doi.org/10.3390/ijms23073997 - 03 Apr 2022

Cited by 3 | Viewed by 2903

Abstract

Within Leydig cells, steroidogenesis is induced by the pituitary luteinizing hormone (LH). The binding of LH to its receptor increases cAMP production, which then activates the expression of genes involved in testosterone biosynthesis. One of these genes codes for the steroidogenic acute regulatory (STAR) protein. STAR is part of a complex that shuttles cholesterol, the precursor of all steroid hormones, through the mitochondrial membrane where steroidogenesis is initiated. Organochlorine chemicals (OCs) are environmental persistent organic pollutants that are found at high concentrations in Arctic areas. OCs are known to affect male reproductive health by decreasing semen quality in different species, including humans. We previously showed that an environmentally relevant mixture of OCs found in Northern Quebec disrupts steroidogenesis by decreasing STAR protein levels without affecting the transcription of the gene. We hypothesized that OCs might affect STAR protein stability. To test this, MA-10 Leydig cell lines were incubated for 6 h with vehicle or the OCs mixture in the presence or absence of 8Br-cAMP with or without MG132, an inhibitor of protein degradation. We found that MG132 prevented the OC-mediated decrease in STAR protein levels following 8Br-cAMP stimulation. However, progesterone production was still decreased by the OC mixture, even in the presence of MG132. This suggested that proteins involved in steroid hormone production in addition to STAR are also affected by the OC mixture. To identify these proteins, a whole cell approach was used and total proteins from MA-10 Leydig cells exposed to the OC mixture with or without stimulation with 8Br-cAMP were analyzed by 2D SDS-PAGE and LC-MS/MS. Bioinformatics analyses revealed that several proteins involved in numerous biological processes are affected by the OC mixture, including proteins involved in mitochondrial transport, lipid metabolism, and steroidogenesis. Full article

(This article belongs to the Special Issue In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions 2.0)

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19 pages, 3355 KiB

Open AccessArticle

Mechanisms of MEHP Inhibitory Action and Analysis of Potential Replacement Plasticizers on Leydig Cell Steroidogenesis

by Annick N. Enangue Njembele and Jacques J. Tremblay

Int. J. Mol. Sci. 2021, 22(21), 11456; https://doi.org/10.3390/ijms222111456 - 24 Oct 2021

Cited by 9 | Viewed by 3449

Abstract

Steroid production in Leydig cells is stimulated mainly by the pituitary luteinizing hormone, which leads to increased expression of genes involved in steroidogenesis, including the gene encoding the steroidogenic acute regulatory (STAR) protein. Mono(2-ethylhexyl)phthalate (MEHP), the active metabolite of the widely used plasticizer DEHP, is known to disrupt Leydig steroidogenesis but its mechanisms of action remain poorly understood. We found that MEHP caused a significant reduction in hormone-induced steroid hormone production in two Leydig cell lines, MA-10 and MLTC-1. Consistent with disrupted cholesterol transport, we found that MEHP represses cAMP-induced Star promoter activity. MEHP responsiveness was mapped to the proximal Star promoter, which contains multiple binding sites for several transcription factors. In addition to STAR, we found that MEHP also reduced the levels of ferredoxin reductase, a protein essential for electron transport during steroidogenesis. Finally, we tested new plasticizers as alternatives to phthalates. Two plasticizers, dioctyl succinate and 1,6-hexanediol dibenzoate, had no significant effect on hormone-induced steroidogenesis. Our current findings reveal that MEHP represses steroidogenesis by affecting cholesterol transport and its conversion into pregnenolone. We also found that two novel molecules with desirable plasticizer properties have no impact on Leydig cell steroidogenesis and could be suitable phthalate replacements. Full article

(This article belongs to the Special Issue In Vivo Steroid Synthesis and Metabolism in Healthy and Pathological Conditions 2.0)

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