Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications
Abstract Androgen deficiency (hypogonadism) affects males of all ages. Testosterone replacement therapy (TRT) is effective in restoring serum testosterone and relieving symptoms. TRT, however, is reported to have possible adverse effects in part because administered testosterone is not produced in r...
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| Veröffentlicht in: | Endocrine reviews 2020-02, Vol.41 (1), p.22-32 |
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| description | Abstract
Androgen deficiency (hypogonadism) affects males of all ages. Testosterone replacement therapy (TRT) is effective in restoring serum testosterone and relieving symptoms. TRT, however, is reported to have possible adverse effects in part because administered testosterone is not produced in response to the hypothalamic–pituitary–gonadal (HPG) axis. Progress in stem cell biology offers potential alternatives for treating hypogonadism. Adult Leydig cells (ALCs) are generated by stem Leydig cells (SLCs) during puberty. SLCs persist in the adult testis. Considerable progress has been made in the identification, isolation, expansion and differentiation of SLCs in vitro. In addition to forming ALCs, SLCs are multipotent, with the ability to give rise to all 3 major cell lineages of typical mesenchymal stem cells, including osteoblasts, adipocytes, and chondrocytes. Several regulatory factors, including Desert hedgehog and platelet-derived growth factor, have been reported to play key roles in the proliferation and differentiation of SLCs into the Leydig lineage. In addition, stem cells from several nonsteroidogenic sources, including embryonic stem cells, induced pluripotent stem cells, mature fibroblasts, and mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord have been transdifferentiated into Leydig-like cells under a variety of induction protocols. ALCs generated from SLCs in vitro, as well as Leydig-like cells, have been successfully transplanted into ALC-depleted animals, restoring serum testosterone levels under HPG control. However, important questions remain, including: How long will the transplanted cells continue to function? Which induction protocol is safest and most effective? For translational purposes, more work is needed with primate cells, especially human.
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| doi_str_mv | 10.1210/endrev/bnz013 |
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| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7753054</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A698914098</galeid><oup_id>10.1210/endrev/bnz013</oup_id><sourcerecordid>A698914098</sourcerecordid><originalsourceid>FETCH-LOGICAL-c581t-4f75c74cef20b4e8eef055dc065334404c47d80a9284caf1d7802e8bfccf84323</originalsourceid><addsrcrecordid>eNqFks9rFDEUx4Modls9epWAFw9Om0wyk8SDsCz-ggVFK3gyZDMvuymzyTSZKbR_fbPdWlsRJIeEvE--ed_HF6EXlBzTmpITCF2Ci5NVuCKUPUIzqnhTCSrVYzQjtGWVaNXPA3SY8xkhhBOpnqIDRlvBWiVm6Nf3EbZ4CZedX-MF9H3GPuBxA3jeTf2ITyGPPr_Fi41Jxo6Q_JUZfQxv8DdYT_3NGZvQ4a9xhDB60-P5MPTe3lTyM_TEmT7D89v9CP348P508alafvn4eTFfVraRdKy4E40V3IKryYqDBHCkaTpL2oYxzgm3XHSSGFVLbo2jnZCkBrly1jrJWc2O0Lu97jCtttDZ0koyvR6S35p0qaPx-mEl-I1exwstRMNIw4vA61uBFM-nYlpvfbZlHiZAnLKuGS3DVFLRgr76Cz2LUwrFnq5Lq0wpwe5Ra9OD9sHF8q_diep5u9PhRMlCHf-DKquDrbcxgPPl_sGDav_ApphzAnfnkRK9C4TeB0LvA1H4l_cHc0f_TsAf43Ea_qN1DTEXwQE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2404399731</pqid></control><display><type>article</type><title>Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><source>ProQuest Central</source><creator>Chen, Panpan ; Zirkin, Barry R ; Chen, Haolin</creator><creatorcontrib>Chen, Panpan ; Zirkin, Barry R ; Chen, Haolin</creatorcontrib><description>Abstract
Androgen deficiency (hypogonadism) affects males of all ages. Testosterone replacement therapy (TRT) is effective in restoring serum testosterone and relieving symptoms. TRT, however, is reported to have possible adverse effects in part because administered testosterone is not produced in response to the hypothalamic–pituitary–gonadal (HPG) axis. Progress in stem cell biology offers potential alternatives for treating hypogonadism. Adult Leydig cells (ALCs) are generated by stem Leydig cells (SLCs) during puberty. SLCs persist in the adult testis. Considerable progress has been made in the identification, isolation, expansion and differentiation of SLCs in vitro. In addition to forming ALCs, SLCs are multipotent, with the ability to give rise to all 3 major cell lineages of typical mesenchymal stem cells, including osteoblasts, adipocytes, and chondrocytes. Several regulatory factors, including Desert hedgehog and platelet-derived growth factor, have been reported to play key roles in the proliferation and differentiation of SLCs into the Leydig lineage. In addition, stem cells from several nonsteroidogenic sources, including embryonic stem cells, induced pluripotent stem cells, mature fibroblasts, and mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord have been transdifferentiated into Leydig-like cells under a variety of induction protocols. ALCs generated from SLCs in vitro, as well as Leydig-like cells, have been successfully transplanted into ALC-depleted animals, restoring serum testosterone levels under HPG control. However, important questions remain, including: How long will the transplanted cells continue to function? Which induction protocol is safest and most effective? For translational purposes, more work is needed with primate cells, especially human.
Graphical Abstract
Graphical Abstract</description><identifier>ISSN: 0163-769X</identifier><identifier>EISSN: 1945-7189</identifier><identifier>DOI: 10.1210/endrev/bnz013</identifier><identifier>PMID: 31673697</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adipocytes ; Adipose tissue ; Adult ; Animals ; Biomedical materials ; Bone marrow ; Cell Differentiation ; Cell Lineage - physiology ; Chondrocytes ; Differentiation ; Embryo cells ; Embryonic stem cells ; Fibroblasts ; Growth factors ; Hormone replacement therapy ; Humans ; Hypogonadism ; Hypogonadism - etiology ; Hypogonadism - pathology ; Hypogonadism - therapy ; Hypothalamus ; Leydig cells ; Leydig Cells - cytology ; Leydig Cells - physiology ; Male ; Mesenchyme ; Osteoblasts ; Pituitary ; Platelet-derived growth factor ; Pluripotency ; Puberty ; Reviews ; Spermatogenesis - physiology ; Stem cell transplantation ; Stem cells ; Stem Cells - cytology ; Stem Cells - physiology ; Testis - cytology ; Testis - physiology ; Testosterone ; Transplantation ; Umbilical cord</subject><ispartof>Endocrine reviews, 2020-02, Vol.41 (1), p.22-32</ispartof><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2019</rights><rights>Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2020 Oxford University Press</rights><rights>Endocrine Society 2019. 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-c581t-4f75c74cef20b4e8eef055dc065334404c47d80a9284caf1d7802e8bfccf84323</citedby><cites>FETCH-LOGICAL-c581t-4f75c74cef20b4e8eef055dc065334404c47d80a9284caf1d7802e8bfccf84323</cites><orcidid>0000-0001-7021-7115</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2404399731?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,776,780,881,21367,27901,27902,33721,33722,43781</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31673697$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Panpan</creatorcontrib><creatorcontrib>Zirkin, Barry R</creatorcontrib><creatorcontrib>Chen, Haolin</creatorcontrib><title>Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications</title><title>Endocrine reviews</title><addtitle>Endocr Rev</addtitle><description>Abstract
Androgen deficiency (hypogonadism) affects males of all ages. Testosterone replacement therapy (TRT) is effective in restoring serum testosterone and relieving symptoms. TRT, however, is reported to have possible adverse effects in part because administered testosterone is not produced in response to the hypothalamic–pituitary–gonadal (HPG) axis. Progress in stem cell biology offers potential alternatives for treating hypogonadism. Adult Leydig cells (ALCs) are generated by stem Leydig cells (SLCs) during puberty. SLCs persist in the adult testis. Considerable progress has been made in the identification, isolation, expansion and differentiation of SLCs in vitro. In addition to forming ALCs, SLCs are multipotent, with the ability to give rise to all 3 major cell lineages of typical mesenchymal stem cells, including osteoblasts, adipocytes, and chondrocytes. Several regulatory factors, including Desert hedgehog and platelet-derived growth factor, have been reported to play key roles in the proliferation and differentiation of SLCs into the Leydig lineage. In addition, stem cells from several nonsteroidogenic sources, including embryonic stem cells, induced pluripotent stem cells, mature fibroblasts, and mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord have been transdifferentiated into Leydig-like cells under a variety of induction protocols. ALCs generated from SLCs in vitro, as well as Leydig-like cells, have been successfully transplanted into ALC-depleted animals, restoring serum testosterone levels under HPG control. However, important questions remain, including: How long will the transplanted cells continue to function? Which induction protocol is safest and most effective? For translational purposes, more work is needed with primate cells, especially human.
Graphical Abstract
Graphical Abstract</description><subject>Adipocytes</subject><subject>Adipose tissue</subject><subject>Adult</subject><subject>Animals</subject><subject>Biomedical materials</subject><subject>Bone marrow</subject><subject>Cell Differentiation</subject><subject>Cell Lineage - physiology</subject><subject>Chondrocytes</subject><subject>Differentiation</subject><subject>Embryo cells</subject><subject>Embryonic stem cells</subject><subject>Fibroblasts</subject><subject>Growth factors</subject><subject>Hormone replacement therapy</subject><subject>Humans</subject><subject>Hypogonadism</subject><subject>Hypogonadism - etiology</subject><subject>Hypogonadism - pathology</subject><subject>Hypogonadism - therapy</subject><subject>Hypothalamus</subject><subject>Leydig cells</subject><subject>Leydig Cells - cytology</subject><subject>Leydig Cells - physiology</subject><subject>Male</subject><subject>Mesenchyme</subject><subject>Osteoblasts</subject><subject>Pituitary</subject><subject>Platelet-derived growth factor</subject><subject>Pluripotency</subject><subject>Puberty</subject><subject>Reviews</subject><subject>Spermatogenesis - physiology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - physiology</subject><subject>Testis - cytology</subject><subject>Testis - physiology</subject><subject>Testosterone</subject><subject>Transplantation</subject><subject>Umbilical cord</subject><issn>0163-769X</issn><issn>1945-7189</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFks9rFDEUx4Modls9epWAFw9Om0wyk8SDsCz-ggVFK3gyZDMvuymzyTSZKbR_fbPdWlsRJIeEvE--ed_HF6EXlBzTmpITCF2Ci5NVuCKUPUIzqnhTCSrVYzQjtGWVaNXPA3SY8xkhhBOpnqIDRlvBWiVm6Nf3EbZ4CZedX-MF9H3GPuBxA3jeTf2ITyGPPr_Fi41Jxo6Q_JUZfQxv8DdYT_3NGZvQ4a9xhDB60-P5MPTe3lTyM_TEmT7D89v9CP348P508alafvn4eTFfVraRdKy4E40V3IKryYqDBHCkaTpL2oYxzgm3XHSSGFVLbo2jnZCkBrly1jrJWc2O0Lu97jCtttDZ0koyvR6S35p0qaPx-mEl-I1exwstRMNIw4vA61uBFM-nYlpvfbZlHiZAnLKuGS3DVFLRgr76Cz2LUwrFnq5Lq0wpwe5Ra9OD9sHF8q_diep5u9PhRMlCHf-DKquDrbcxgPPl_sGDav_ApphzAnfnkRK9C4TeB0LvA1H4l_cHc0f_TsAf43Ea_qN1DTEXwQE</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Chen, Panpan</creator><creator>Zirkin, Barry R</creator><creator>Chen, Haolin</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7021-7115</orcidid></search><sort><creationdate>20200201</creationdate><title>Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications</title><author>Chen, Panpan ; Zirkin, Barry R ; Chen, Haolin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c581t-4f75c74cef20b4e8eef055dc065334404c47d80a9284caf1d7802e8bfccf84323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adipocytes</topic><topic>Adipose tissue</topic><topic>Adult</topic><topic>Animals</topic><topic>Biomedical materials</topic><topic>Bone marrow</topic><topic>Cell Differentiation</topic><topic>Cell Lineage - physiology</topic><topic>Chondrocytes</topic><topic>Differentiation</topic><topic>Embryo cells</topic><topic>Embryonic stem cells</topic><topic>Fibroblasts</topic><topic>Growth factors</topic><topic>Hormone replacement therapy</topic><topic>Humans</topic><topic>Hypogonadism</topic><topic>Hypogonadism - etiology</topic><topic>Hypogonadism - pathology</topic><topic>Hypogonadism - therapy</topic><topic>Hypothalamus</topic><topic>Leydig cells</topic><topic>Leydig Cells - cytology</topic><topic>Leydig Cells - physiology</topic><topic>Male</topic><topic>Mesenchyme</topic><topic>Osteoblasts</topic><topic>Pituitary</topic><topic>Platelet-derived growth factor</topic><topic>Pluripotency</topic><topic>Puberty</topic><topic>Reviews</topic><topic>Spermatogenesis - physiology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - physiology</topic><topic>Testis - cytology</topic><topic>Testis - physiology</topic><topic>Testosterone</topic><topic>Transplantation</topic><topic>Umbilical cord</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Panpan</creatorcontrib><creatorcontrib>Zirkin, Barry R</creatorcontrib><creatorcontrib>Chen, Haolin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Endocrine reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Panpan</au><au>Zirkin, Barry R</au><au>Chen, Haolin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications</atitle><jtitle>Endocrine reviews</jtitle><addtitle>Endocr Rev</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>41</volume><issue>1</issue><spage>22</spage><epage>32</epage><pages>22-32</pages><issn>0163-769X</issn><eissn>1945-7189</eissn><abstract>Abstract
Androgen deficiency (hypogonadism) affects males of all ages. Testosterone replacement therapy (TRT) is effective in restoring serum testosterone and relieving symptoms. TRT, however, is reported to have possible adverse effects in part because administered testosterone is not produced in response to the hypothalamic–pituitary–gonadal (HPG) axis. Progress in stem cell biology offers potential alternatives for treating hypogonadism. Adult Leydig cells (ALCs) are generated by stem Leydig cells (SLCs) during puberty. SLCs persist in the adult testis. Considerable progress has been made in the identification, isolation, expansion and differentiation of SLCs in vitro. In addition to forming ALCs, SLCs are multipotent, with the ability to give rise to all 3 major cell lineages of typical mesenchymal stem cells, including osteoblasts, adipocytes, and chondrocytes. Several regulatory factors, including Desert hedgehog and platelet-derived growth factor, have been reported to play key roles in the proliferation and differentiation of SLCs into the Leydig lineage. In addition, stem cells from several nonsteroidogenic sources, including embryonic stem cells, induced pluripotent stem cells, mature fibroblasts, and mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord have been transdifferentiated into Leydig-like cells under a variety of induction protocols. ALCs generated from SLCs in vitro, as well as Leydig-like cells, have been successfully transplanted into ALC-depleted animals, restoring serum testosterone levels under HPG control. However, important questions remain, including: How long will the transplanted cells continue to function? Which induction protocol is safest and most effective? For translational purposes, more work is needed with primate cells, especially human.
Graphical Abstract
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| subjects | Adipocytes Adipose tissue Adult Animals Biomedical materials Bone marrow Cell Differentiation Cell Lineage - physiology Chondrocytes Differentiation Embryo cells Embryonic stem cells Fibroblasts Growth factors Hormone replacement therapy Humans Hypogonadism Hypogonadism - etiology Hypogonadism - pathology Hypogonadism - therapy Hypothalamus Leydig cells Leydig Cells - cytology Leydig Cells - physiology Male Mesenchyme Osteoblasts Pituitary Platelet-derived growth factor Pluripotency Puberty Reviews Spermatogenesis - physiology Stem cell transplantation Stem cells Stem Cells - cytology Stem Cells - physiology Testis - cytology Testis - physiology Testosterone Transplantation Umbilical cord |
| title | Stem Leydig Cells in the Adult Testis: Characterization, Regulation and Potential Applications |
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