Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling
Two specialized functions of cholesterol during fetal development include serving as a precursor to androgen synthesis and supporting hedgehog (HH) signaling activity. Androgens are produced by the testes to facilitate masculinization of the fetus. Recent evidence shows that intricate interactions b...
Gespeichert in:
| Veröffentlicht in: | Endocrinology (Philadelphia) 2021-07, Vol.162 (7), p.1 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 7 |
| container_start_page | 1 |
| container_title | Endocrinology (Philadelphia) |
| container_volume | 162 |
| creator | Kothandapani, Anbarasi Jefcoate, Colin R Jorgensen, Joan S |
| description | Two specialized functions of cholesterol during fetal development include serving as a precursor to androgen synthesis and supporting hedgehog (HH) signaling activity. Androgens are produced by the testes to facilitate masculinization of the fetus. Recent evidence shows that intricate interactions between the HH and androgen signaling pathways are required for optimal male sex differentiation and defects of either can cause birth anomalies indicative of 46,XY male variations of sex development (VSD). Further, perturbations in cholesterol synthesis can cause developmental defects, including VSD, that phenocopy those caused by disrupted androgen or HH signaling, highlighting the functional role of cholesterol in promoting male sex differentiation. In this review, we focus on the role of cholesterol in systemic androgen and local HH signaling events during fetal masculinization and their collective contributions to pediatric VSD. |
| doi_str_mv | 10.1210/endocr/bqab066 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8168945</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A775899165</galeid><oup_id>10.1210/endocr/bqab066</oup_id><sourcerecordid>A775899165</sourcerecordid><originalsourceid>FETCH-LOGICAL-c519t-da640fb8ee54b4ab3c2e9653ad969729294f1506cf05e7a9765f3651e3067d8e3</originalsourceid><addsrcrecordid>eNqFks9rFDEUx4Modq1ePUrASz1Mm8xMkslFWLZqCxXBreeQmXmZSckm22Sm2JP_ull2rT8oSHiE5H3eN3lfHkKvKTmlJSVn4PvQxbP2VreE8ydoQWXNCkEFeYoWhNCqEGUpjtCLlG7ysa7r6jk6qirR1DkW6MdqDA7SBDE4vAp-iradJ0h4CvizdoDX8B2fW2Mggp-snmzw-HqMYR5GfDklfA534MJ2k7Pa4a9ZDFuPl76PYQCP1_d-GiHZhLXv8QX0A4xhwGs7eO2sH16iZ0a7BK8O-zH69vHD9eqiuPry6XK1vCo6RuVU9JrXxLQNAKvbWrdVV4LkrNK95FKUspS1oYzwzhAGQkvBmak4o1ARLvoGqmP0fq-7ndsN9F3-btRObaPd6Hivgrbq74y3oxrCnWoob7KlWeDkIBDD7ZwdUxubOnBOewhzUiUjgvMmR0bf_oPehDnmfjPVSMqZYJz8poZss7LehPxutxNVSyFYI3dkpk4fofLqYWO74MHYfP9YQRdDShHMQ4-UqN3IqP3IqMPI5II3fzrzgP-akQy82wNh3v5P7CcBbM4S</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2891657560</pqid></control><display><type>article</type><title>Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Kothandapani, Anbarasi ; Jefcoate, Colin R ; Jorgensen, Joan S</creator><creatorcontrib>Kothandapani, Anbarasi ; Jefcoate, Colin R ; Jorgensen, Joan S</creatorcontrib><description>Two specialized functions of cholesterol during fetal development include serving as a precursor to androgen synthesis and supporting hedgehog (HH) signaling activity. Androgens are produced by the testes to facilitate masculinization of the fetus. Recent evidence shows that intricate interactions between the HH and androgen signaling pathways are required for optimal male sex differentiation and defects of either can cause birth anomalies indicative of 46,XY male variations of sex development (VSD). Further, perturbations in cholesterol synthesis can cause developmental defects, including VSD, that phenocopy those caused by disrupted androgen or HH signaling, highlighting the functional role of cholesterol in promoting male sex differentiation. In this review, we focus on the role of cholesterol in systemic androgen and local HH signaling events during fetal masculinization and their collective contributions to pediatric VSD.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/endocr/bqab066</identifier><identifier>PMID: 33784378</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Analysis ; Androgens ; Androgens - biosynthesis ; Animals ; Anomalies ; Antilipemic agents ; Birth defects ; Cholesterol ; Cholesterol - biosynthesis ; Cholesterol - physiology ; Defects ; Development and progression ; Differences of sex development ; Differentiation ; Disorders of Sex Development ; Endocrinology ; Fetal Development - physiology ; Fetus ; Fetus - metabolism ; Fetuses ; Growth ; Hedgehog protein ; Hedgehog Proteins - metabolism ; Humans ; Leydig Cells - physiology ; Male ; Males ; Mini-Reviews ; Pediatrics ; Sex ; Sex differentiation ; Sex Differentiation - physiology ; Signal Transduction - physiology ; Synthesis ; Testis - embryology ; Testis - metabolism</subject><ispartof>Endocrinology (Philadelphia), 2021-07, Vol.162 (7), p.1</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2021 Oxford University Press</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-da640fb8ee54b4ab3c2e9653ad969729294f1506cf05e7a9765f3651e3067d8e3</citedby><cites>FETCH-LOGICAL-c519t-da640fb8ee54b4ab3c2e9653ad969729294f1506cf05e7a9765f3651e3067d8e3</cites><orcidid>0000-0001-9701-0800 ; 0000-0002-5787-8856</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33784378$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kothandapani, Anbarasi</creatorcontrib><creatorcontrib>Jefcoate, Colin R</creatorcontrib><creatorcontrib>Jorgensen, Joan S</creatorcontrib><title>Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Two specialized functions of cholesterol during fetal development include serving as a precursor to androgen synthesis and supporting hedgehog (HH) signaling activity. Androgens are produced by the testes to facilitate masculinization of the fetus. Recent evidence shows that intricate interactions between the HH and androgen signaling pathways are required for optimal male sex differentiation and defects of either can cause birth anomalies indicative of 46,XY male variations of sex development (VSD). Further, perturbations in cholesterol synthesis can cause developmental defects, including VSD, that phenocopy those caused by disrupted androgen or HH signaling, highlighting the functional role of cholesterol in promoting male sex differentiation. In this review, we focus on the role of cholesterol in systemic androgen and local HH signaling events during fetal masculinization and their collective contributions to pediatric VSD.</description><subject>Analysis</subject><subject>Androgens</subject><subject>Androgens - biosynthesis</subject><subject>Animals</subject><subject>Anomalies</subject><subject>Antilipemic agents</subject><subject>Birth defects</subject><subject>Cholesterol</subject><subject>Cholesterol - biosynthesis</subject><subject>Cholesterol - physiology</subject><subject>Defects</subject><subject>Development and progression</subject><subject>Differences of sex development</subject><subject>Differentiation</subject><subject>Disorders of Sex Development</subject><subject>Endocrinology</subject><subject>Fetal Development - physiology</subject><subject>Fetus</subject><subject>Fetus - metabolism</subject><subject>Fetuses</subject><subject>Growth</subject><subject>Hedgehog protein</subject><subject>Hedgehog Proteins - metabolism</subject><subject>Humans</subject><subject>Leydig Cells - physiology</subject><subject>Male</subject><subject>Males</subject><subject>Mini-Reviews</subject><subject>Pediatrics</subject><subject>Sex</subject><subject>Sex differentiation</subject><subject>Sex Differentiation - physiology</subject><subject>Signal Transduction - physiology</subject><subject>Synthesis</subject><subject>Testis - embryology</subject><subject>Testis - metabolism</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9rFDEUx4Modq1ePUrASz1Mm8xMkslFWLZqCxXBreeQmXmZSckm22Sm2JP_ull2rT8oSHiE5H3eN3lfHkKvKTmlJSVn4PvQxbP2VreE8ydoQWXNCkEFeYoWhNCqEGUpjtCLlG7ysa7r6jk6qirR1DkW6MdqDA7SBDE4vAp-iradJ0h4CvizdoDX8B2fW2Mggp-snmzw-HqMYR5GfDklfA534MJ2k7Pa4a9ZDFuPl76PYQCP1_d-GiHZhLXv8QX0A4xhwGs7eO2sH16iZ0a7BK8O-zH69vHD9eqiuPry6XK1vCo6RuVU9JrXxLQNAKvbWrdVV4LkrNK95FKUspS1oYzwzhAGQkvBmak4o1ARLvoGqmP0fq-7ndsN9F3-btRObaPd6Hivgrbq74y3oxrCnWoob7KlWeDkIBDD7ZwdUxubOnBOewhzUiUjgvMmR0bf_oPehDnmfjPVSMqZYJz8poZss7LehPxutxNVSyFYI3dkpk4fofLqYWO74MHYfP9YQRdDShHMQ4-UqN3IqP3IqMPI5II3fzrzgP-akQy82wNh3v5P7CcBbM4S</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Kothandapani, Anbarasi</creator><creator>Jefcoate, Colin R</creator><creator>Jorgensen, Joan S</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9701-0800</orcidid><orcidid>https://orcid.org/0000-0002-5787-8856</orcidid></search><sort><creationdate>20210701</creationdate><title>Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling</title><author>Kothandapani, Anbarasi ; Jefcoate, Colin R ; Jorgensen, Joan S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-da640fb8ee54b4ab3c2e9653ad969729294f1506cf05e7a9765f3651e3067d8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Androgens</topic><topic>Androgens - biosynthesis</topic><topic>Animals</topic><topic>Anomalies</topic><topic>Antilipemic agents</topic><topic>Birth defects</topic><topic>Cholesterol</topic><topic>Cholesterol - biosynthesis</topic><topic>Cholesterol - physiology</topic><topic>Defects</topic><topic>Development and progression</topic><topic>Differences of sex development</topic><topic>Differentiation</topic><topic>Disorders of Sex Development</topic><topic>Endocrinology</topic><topic>Fetal Development - physiology</topic><topic>Fetus</topic><topic>Fetus - metabolism</topic><topic>Fetuses</topic><topic>Growth</topic><topic>Hedgehog protein</topic><topic>Hedgehog Proteins - metabolism</topic><topic>Humans</topic><topic>Leydig Cells - physiology</topic><topic>Male</topic><topic>Males</topic><topic>Mini-Reviews</topic><topic>Pediatrics</topic><topic>Sex</topic><topic>Sex differentiation</topic><topic>Sex Differentiation - physiology</topic><topic>Signal Transduction - physiology</topic><topic>Synthesis</topic><topic>Testis - embryology</topic><topic>Testis - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kothandapani, Anbarasi</creatorcontrib><creatorcontrib>Jefcoate, Colin R</creatorcontrib><creatorcontrib>Jorgensen, Joan S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kothandapani, Anbarasi</au><au>Jefcoate, Colin R</au><au>Jorgensen, Joan S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>162</volume><issue>7</issue><spage>1</spage><pages>1-</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>Two specialized functions of cholesterol during fetal development include serving as a precursor to androgen synthesis and supporting hedgehog (HH) signaling activity. Androgens are produced by the testes to facilitate masculinization of the fetus. Recent evidence shows that intricate interactions between the HH and androgen signaling pathways are required for optimal male sex differentiation and defects of either can cause birth anomalies indicative of 46,XY male variations of sex development (VSD). Further, perturbations in cholesterol synthesis can cause developmental defects, including VSD, that phenocopy those caused by disrupted androgen or HH signaling, highlighting the functional role of cholesterol in promoting male sex differentiation. In this review, we focus on the role of cholesterol in systemic androgen and local HH signaling events during fetal masculinization and their collective contributions to pediatric VSD.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33784378</pmid><doi>10.1210/endocr/bqab066</doi><orcidid>https://orcid.org/0000-0001-9701-0800</orcidid><orcidid>https://orcid.org/0000-0002-5787-8856</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0013-7227 |
| ispartof | Endocrinology (Philadelphia), 2021-07, Vol.162 (7), p.1 |
| issn | 0013-7227 1945-7170 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8168945 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Analysis Androgens Androgens - biosynthesis Animals Anomalies Antilipemic agents Birth defects Cholesterol Cholesterol - biosynthesis Cholesterol - physiology Defects Development and progression Differences of sex development Differentiation Disorders of Sex Development Endocrinology Fetal Development - physiology Fetus Fetus - metabolism Fetuses Growth Hedgehog protein Hedgehog Proteins - metabolism Humans Leydig Cells - physiology Male Males Mini-Reviews Pediatrics Sex Sex differentiation Sex Differentiation - physiology Signal Transduction - physiology Synthesis Testis - embryology Testis - metabolism |
| title | Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T18%3A45%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cholesterol%20Contributes%20to%20Male%20Sex%20Differentiation%20Through%20Its%20Developmental%20Role%20in%20Androgen%20Synthesis%20and%20Hedgehog%20Signaling&rft.jtitle=Endocrinology%20(Philadelphia)&rft.au=Kothandapani,%20Anbarasi&rft.date=2021-07-01&rft.volume=162&rft.issue=7&rft.spage=1&rft.pages=1-&rft.issn=0013-7227&rft.eissn=1945-7170&rft_id=info:doi/10.1210/endocr/bqab066&rft_dat=%3Cgale_pubme%3EA775899165%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2891657560&rft_id=info:pmid/33784378&rft_galeid=A775899165&rft_oup_id=10.1210/endocr/bqab066&rfr_iscdi=true |