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{"title"=>"Fsh Controls Gene Expression in Fish both Independently of and through Steroid Mediation", "type"=>"journal", "authors"=>[{"first_name"=>"Elisabeth", "last_name"=>"Sambroni", "scopus_author_id"=>"6506070871"}, {"first_name"=>"Jean Jacques", "last_name"=>"Lareyre", "scopus_author_id"=>"6701608663"}, {"first_name"=>"Florence", "last_name"=>"Le Gac", "scopus_author_id"=>"6701423681"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84886078858", "doi"=>"10.1371/journal.pone.0076684", "isbn"=>"1932-6203", "pmid"=>"24194844", "issn"=>"19326203", "scopus"=>"2-s2.0-84886078858", "pui"=>"370091161"}, "id"=>"8b695d62-08f7-38ba-8e2b-261790931eca", "abstract"=>"The mechanisms and the mediators relaying Fsh action on testicular functions are poorly understood. Unlike in mammals, in fish both gonadotropins (Fsh and Lh) are able to efficiently stimulate steroidogenesis, likely through a direct interaction with their cognate receptors present on the Leydig cells. In this context, it is crucial to understand if Fsh effects are mediated through the production of steroids. To address this issue we performed transcriptome studies after in vitro incubations of rainbow trout testis explants in the presence of Fsh alone or in combination with trilostane, an inhibitor of Δ4- steroidogenesis. Trilostane significantly reduced or suppressed the response of many genes to Fsh (like wisp1, testis gapdhs, cldn11, inha, vt1 or dmrt1) showing that, in fish, important aspects of Fsh action follow indirect pathways and require the production of Δ4-steroids. What is more, most of the genes regulated by Fsh through steroid mediation were similarly regulated by Lh (and/or androgens). In contrast, the response to Fsh of other genes was not suppressed in the presence of trilostane. These latter included genes encoding for anti-mullerian hormone, midkine a (pleiotrophin related), angiopoietine-related protein, cyclins E1 and G1, hepatocyte growth factor activator, insulin-like growth factor 1b/3. A majority of those genes were preferentially regulated by Fsh, when compared to Lh, suggesting that specific regulatory effects of Fsh did not depend on steroid production. Finally, antagonistic effects between Fsh and steroids were found, in particular for genes encoding key factors of steroidogenesis (star, hsd3b1, cyp11b2-2) or for genes of the Igf system (igf1b/3). Our study provides the first clear evidence that, in fish, Fsh exerts Δ4-steroid-independent regulatory functions on many genes which are highly relevant for the onset of spermatogenesis.", "link"=>"http://www.mendeley.com/research/fsh-controls-gene-expression-fish-both-independently-through-steroid-mediation", "reader_count"=>36, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Student > Doctoral Student"=>4, "Researcher"=>5, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>6, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Student > Doctoral Student"=>4, "Researcher"=>5, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>6, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>2, "Neuroscience"=>1, "Chemistry"=>1, "Social Sciences"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "Mexico"=>1}, "group_count"=>0}

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• http://doi.org/10.1002/mrd.22752
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• http://doi.org/10.1016/j.ygcen.2019.04.020
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• http://doi.org/10.3389/fendo.2019.00304
• http://doi.org/10.1016/j.ygcen.2014.11.015

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• {"files"=>["https://ndownloader.figshare.com/files/1256163"], "description"=>"<p>Relative expression of selected mRNA transcripts in testicular explants cultured during 4 days in the absence (Ctrl) or presence of either Fsh (500 ng/mL), 11-ketotestosterone (11KT) or 17α-methyltestosterone (MT) at 300 ng/mL (∼10⁻⁶ M). Bars represent mean ± SD of 5 to 6 replicates. Expression data were normalized to the reference gene <i>rps15</i>. Different letters indicate that treatments are significantly different as determined by non-parametric Mann & Whitney test.</p>", "links"=>[], "tags"=>["pcr"], "article_id"=>831085, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g005", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Real_time_PCR_measurement_of_candidate_gene_expression_/831085", "title"=>"Real-time PCR measurement of candidate gene expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256157"], "description"=>"<p>Heatmap representation of the hierarchical classification of the 102 clones differentially regulated in trout testis after an <i>in vitro</i> 4-day incubation without any substance (Ctrl) or with Fsh alone at 500 ng/mL (Fsh), trilostane alone at 10 µg/mL (Tri) or with both Fsh and trilostane (Fsh+Tri). Trilostane was added 1 h before Fsh addition in the medium. Media and hormones were renewed after 2 days. Clones segregated into 5 main groups, corresponding to genes which were up- or down-regulated by Fsh and sensitive or not to trilostane. Normalized expression values are shown according to the scale bar. Each line represents a clone and each column is a sample.</p>", "links"=>[], "tags"=>["fsh-responsive"], "article_id"=>831081, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_Fsh_responsive_genes_/831081", "title"=>"Expression of Fsh-responsive genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256156"], "description"=>"<p>11KT production in culture media after 48(500 ng/mL) alone or in combination with trilostane (10 µg/mL). Culture media were replaced after 48 h. Each bar represents the mean ± SD of 6 replicates. Different letters for each incubation duration indicate that treatments have significantly different effects as determined by non-parametric Mann & Whitney test (p<0.01).</p>", "links"=>[], "tags"=>["trilostane"], "article_id"=>831080, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_trilostane_treatment_efficiency_/831080", "title"=>"Evaluation of trilostane treatment efficiency.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256183"], "description"=>"<p>1- The primary action of Fsh is to stimulate steroidogenic cells to produce steroids which in turn regulate gene expression. 2- Fsh exerts specific regulatory effects independently of steroid mediation. 2 bis- In some cases steroids could have either an antagonistic or a redundant effect on gene expression. Plain lines with an arrow head indicate stimulatory effects whereas dotted lines illustrate inhibitory effects.</p>", "links"=>[], "tags"=>["mechanisms", "fsh", "rainbow", "trout"], "article_id"=>831093, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g008", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_mechanisms_underlying_Fsh_action_on_gene_expression_in_rainbow_trout_testis_/831093", "title"=>"Summary of the mechanisms underlying Fsh action on gene expression in rainbow trout testis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256182"], "description"=>"<p>Meta-analysis: heatmap representation of the unsupervised hierarchical classification of the 58 clones found regulated by Fsh in the present study and in our previous study where Fsh and Lh effects on testicular transcriptome were measured (Sambroni et al., 2013).</p>", "links"=>[], "tags"=>["heatmap", "unsupervised", "hierarchical", "classification", "58", "clones", "regulated", "fsh", "lh", "testicular", "transcriptome", "et"], "article_id"=>831092, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g007", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Meta_analysis_heatmap_representation_of_the_unsupervised_hierarchical_classification_of_the_58_clones_found_regulated_by_Fsh_in_the_present_study_and_in_our_previous_study_where_Fsh_and_Lh_effects_on_testicular_transcriptome_were_measured_Sambroni_et_al_/831092", "title"=>"Meta-analysis: heatmap representation of the unsupervised hierarchical classification of the 58 clones found regulated by Fsh in the present study and in our previous study where Fsh and Lh effects on testicular transcriptome were measured (Sambroni et al., 2013).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256176"], "description"=>"<p>The <i>mdka</i> and <i>hsd3b1</i> genes belong to Cluster 2 and the <i>amh</i> gene is segregated in Cluster 5. Four additional candidates previously demonstrated as being regulated by gonadotropins - <i>ccnd1</i>, <i>fstl3</i>, <i>igf1b/igf3</i> and <i>cyp11b2-2</i> - behave like genes of Cluster 2. Furthermore an increased response to Fsh in the presence of trilostane suggests an antagonism between Fsh and the Δ4- steroids. Bars represent mean ± SD of 5 to 6 replicates. Expression data were normalized to the reference gene <i>rps15</i>.</p>", "links"=>[], "tags"=>["fsh", "steady-state", "mrna", "transcripts"], "article_id"=>831086, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g006", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Steroid_independent_action_of_Fsh_on_the_steady_state_level_of_mRNA_transcripts_measured_by_qPCR_/831086", "title"=>"Steroid-independent action of Fsh on the steady-state level of mRNA transcripts measured by qPCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256159"], "description"=>"<p><i>slc26a4</i>, <i>vt1</i>, <i>mmp19</i> and <i>wisp1</i> and <i>inha</i> genes segregate in Cluster 1. The <i>inhba</i> gene belongs to Cluster 4. Three additional transcripts (<i>fshr</i>, <i>lhcgr</i> and <i>igfbp6</i>) previously demonstrated as up-regulated by gonadotropins are found to behave like genes in Cluster 1. Note that Fsh regulations of <i>inha</i>, <i>wisp1</i> and <i>igfbp6</i> are only partially lost in the presence of Tri. Bars represent mean ± SD of 5 to 6 replicates. Expression data were normalized to the reference gene <i>rps15</i>. Different letters indicate that treatments are significantly different as determined by non-parametric Mann & Whitney test.</p>", "links"=>[], "tags"=>["fsh", "steady-state", "mrna", "transcripts"], "article_id"=>831083, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Steroid_mediated_action_of_Fsh_on_the_steady_state_level_of_mRNA_transcripts_measured_by_qPCR_/831083", "title"=>"Steroid-mediated action of Fsh on the steady-state level of mRNA transcripts measured by qPCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256187", "https://ndownloader.figshare.com/files/1256188"], "description"=>"<div><p>The mechanisms and the mediators relaying Fsh action on testicular functions are poorly understood. Unlike in mammals, in fish both gonadotropins (Fsh and Lh) are able to efficiently stimulate steroidogenesis, likely through a direct interaction with their cognate receptors present on the Leydig cells. In this context, it is crucial to understand if Fsh effects are mediated through the production of steroids. To address this issue we performed transcriptome studies after <i>in vitro</i> incubations of rainbow trout testis explants in the presence of Fsh alone or in combination with trilostane, an inhibitor of Δ4- steroidogenesis.</p><p>Trilostane significantly reduced or suppressed the response of many genes to Fsh (like <i>wisp1</i>, testis <i>gapdhs</i>, <i>cldn11</i>, <i>inha</i>, <i>vt1</i> or <i>dmrt1</i>) showing that, in fish, important aspects of Fsh action follow indirect pathways and require the production of Δ4-steroids. What is more, most of the genes regulated by Fsh through steroid mediation were similarly regulated by Lh (and/or androgens). In contrast, the response to Fsh of other genes was not suppressed in the presence of trilostane. These latter included genes encoding for anti-mullerian hormone, midkine a (pleiotrophin related), angiopoietine-related protein, cyclins E1 and G1, hepatocyte growth factor activator, insulin-like growth factor 1b/3. A majority of those genes were preferentially regulated by Fsh, when compared to Lh, suggesting that specific regulatory effects of Fsh did not depend on steroid production. Finally, antagonistic effects between Fsh and steroids were found, in particular for genes encoding key factors of steroidogenesis (<i>star</i>, <i>hsd3b1</i>, <i>cyp11b2-2</i>) or for genes of the Igf system (<i>igf1b/3</i>). Our study provides the first clear evidence that, in fish, Fsh exerts Δ4-steroid-independent regulatory functions on many genes which are highly relevant for the onset of spermatogenesis.</p></div>", "links"=>[], "tags"=>["controls", "independently", "steroid"], "article_id"=>831097, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0076684.s001", "https://dx.doi.org/10.1371/journal.pone.0076684.s002"], "stats"=>{"downloads"=>11, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fsh_Controls_Gene_Expression_in_Fish_both_Independently_of_and_through_Steroid_Mediation_/831097", "title"=>"Fsh Controls Gene Expression in Fish both Independently of and through Steroid Mediation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256158"], "description"=>"<p>Fold changes are relative to the control group. All the 102 clones included were individually found significantly affected by Fsh. Bars represent mean ± SEM. Y-axis is log-2 scaled and value 1 represents the control level. For convenience, note that the clusters are not shown in numerically ascending order.</p>", "links"=>[], "tags"=>["fold-change"], "article_id"=>831082, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.g003", "stats"=>{"downloads"=>3, "page_views"=>41, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representation_of_the_mean_fold_change_in_each_cluster_/831082", "title"=>"Representation of the mean fold-change in each cluster.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256185"], "description"=>"<p>Up-regulated genes mostly segregated in Cluster 2 whereas down-regulated genes segregated in Cluster 5. The response to Fsh was further identified as insensitive to trilostane in pairwise comparisons (Limma statistical test, p≤5%). When the information was available, we indicated the response to Lh (<b>¹</b>) Sambroni et al., 2013), the testicular expression profile as well as the <i>in vivo</i> regulation by androgens ((<b>²</b>)Rolland et al., 2009 and (<b>³</b>) Rolland et al., 2013). -: not determined.</p>", "links"=>[], "tags"=>["transcripts", "regulated", "fsh", "independently"], "article_id"=>831095, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.t003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_transcripts_regulated_by_Fsh_independently_of_916_4_steroid_production_/831095", "title"=>"Representative transcripts regulated by Fsh independently of Δ4-steroid production.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256186"], "description"=>"<p>The corresponding genes segregated in Clusters 1or 2 and the response to Fsh was further identified as highly or moderately sensitive to trilostane in pairwise comparisons (Limma statistical test, p≤5%). When the information was available, we indicated the response to Lh (<b>¹</b>) Sambroni et al., 2013), the testicular expression profile as well as the <i>in vivo</i> regulation by androgens ((²)Rolland et al., 2009 and (³) Rolland et al., 2013). -: not determined.</p>", "links"=>[], "tags"=>["transcripts", "up-regulated", "fsh", "trilostane"], "article_id"=>831096, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.t002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_transcripts_up_regulated_by_Fsh_and_sensitive_to_trilostane_treatment_/831096", "title"=>"Representative transcripts up-regulated by Fsh and sensitive to trilostane treatment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-10-23 03:23:09"}
• {"files"=>["https://ndownloader.figshare.com/files/1256184"], "description"=>"<p>These genes were of interest since they were previously found to be differentially regulated by gonadotropins (Sambroni et al., 2013).</p>", "links"=>[], "tags"=>["genes", "studied"], "article_id"=>831094, "categories"=>["Biological Sciences"], "users"=>["Elisabeth Sambroni", "Jean-Jacques Lareyre", "Florence Le Gac"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0076684.t001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Additional_candidate_genes_studied_using_qPCR_/831094", "title"=>"Additional candidate genes studied using qPCR.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-10-23 03:23:09"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime