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Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries
The elevated insulin concentrations that occur in many women with polycystic ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism. The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between pol...
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Published in: | Molecular human reproduction 2004-07, Vol.10 (7), p.473-479 |
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description | The elevated insulin concentrations that occur in many women with polycystic ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism. The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between polycystic ovaries and regular cycling controls. Individual follicles \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((3{\mbox{--}}7{\,}mm)\) \end{document} were obtained from 11 women with PCOS and 10 regularly cycling control women. The theca and granulosa cells were microdissected from each follicle. Total protein was extracted and signalling proteins were measured by western blot analysis. There was no difference in insulin receptor content between PCOS and controls in either theca or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathit{P}{ |
doi_str_mv | 10.1093/molehr/gah066 |
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The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between polycystic ovaries and regular cycling controls. Individual follicles \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((3{\mbox{--}}7{\,}mm)\) \end{document} were obtained from 11 women with PCOS and 10 regularly cycling control women. The theca and granulosa cells were microdissected from each follicle. Total protein was extracted and signalling proteins were measured by western blot analysis. There was no difference in insulin receptor content between PCOS and controls in either theca or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathit{P}{<}0.05),\) \end{document} but IRS-4 was decreased \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathit{P}{<}0.03)\) \end{document} in PCOS theca cells. There were no changes in IRS-1, -2 or -4 in granulosa cells. IRS-3 was undetectable in all samples. There were no changes in phosphatidyl inositol-3 kinase catalytic subunits p110α or p110β in either theca or granulosa cells. These data demonstrate cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia.</description><identifier>ISSN: 1360-9947</identifier><identifier>ISSN: 1460-2407</identifier><identifier>EISSN: 1460-2407</identifier><identifier>DOI: 10.1093/molehr/gah066</identifier><identifier>PMID: 15155816</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adaptor Proteins, Signal Transducing ; Adult ; Animals ; Biological and medical sciences ; Embryology: invertebrates and vertebrates. Teratology ; Female ; Fundamental and applied biological sciences. Psychology ; granulosa cell ; Granulosa Cells - cytology ; Granulosa Cells - metabolism ; Humans ; Insulin - metabolism ; insulin receptor substrate ; Insulin Receptor Substrate Proteins ; insulin signalling ; Intracellular Signaling Peptides and Proteins ; PCOS ; Phosphoproteins - metabolism ; Polycystic Ovary Syndrome - metabolism ; Receptor, Insulin - metabolism ; Signal Transduction - physiology ; theca cell ; Theca Cells - cytology ; Theca Cells - metabolism</subject><ispartof>Molecular human reproduction, 2004-07, Vol.10 (7), p.473-479</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Jul 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-8a681177abac34a884d9da7395892a0299e0fe1dd6c6454eb5fb7fb911c7e20a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16057723$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15155816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yen, H-W.</creatorcontrib><creatorcontrib>Jakimiuk, A.J.</creatorcontrib><creatorcontrib>Munir, I.</creatorcontrib><creatorcontrib>Magoffin, D.A.</creatorcontrib><title>Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries</title><title>Molecular human reproduction</title><addtitle>Mol. Hum. Reprod</addtitle><description>The elevated insulin concentrations that occur in many women with polycystic ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism. The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between polycystic ovaries and regular cycling controls. Individual follicles \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((3{\mbox{--}}7{\,}mm)\) \end{document} were obtained from 11 women with PCOS and 10 regularly cycling control women. The theca and granulosa cells were microdissected from each follicle. Total protein was extracted and signalling proteins were measured by western blot analysis. There was no difference in insulin receptor content between PCOS and controls in either theca or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathit{P}{<}0.05),\) \end{document} but IRS-4 was decreased \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathit{P}{<}0.03)\) \end{document} in PCOS theca cells. There were no changes in IRS-1, -2 or -4 in granulosa cells. IRS-3 was undetectable in all samples. There were no changes in phosphatidyl inositol-3 kinase catalytic subunits p110α or p110β in either theca or granulosa cells. These data demonstrate cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Adult</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>granulosa cell</subject><subject>Granulosa Cells - cytology</subject><subject>Granulosa Cells - metabolism</subject><subject>Humans</subject><subject>Insulin - metabolism</subject><subject>insulin receptor substrate</subject><subject>Insulin Receptor Substrate Proteins</subject><subject>insulin signalling</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>PCOS</subject><subject>Phosphoproteins - metabolism</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Receptor, Insulin - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>theca cell</subject><subject>Theca Cells - cytology</subject><subject>Theca Cells - metabolism</subject><issn>1360-9947</issn><issn>1460-2407</issn><issn>1460-2407</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqF0c9rFDEUB_BBFFurR68SBHtybJLJj5mj1OoKFRUrFS_hTeZNd-rsZM3LFNe_3iy7uOBFCLwH-eTntyieCv5K8KY6W4URl_HsBpbcmHvFsVCGl1Jxez_3Ve6bRtmj4hHRLefCSl0_LI6EFlrXwhwXv7_giD4Nd8hgTBghDWEiNkx50DzmGtHjOoXIaG4pZYBUipeslAymjpVqa9MSPbB2TmwKid1EmOYxEDCP40isj2HF1mHc-A2lwbNwB3FAelw86GEkfLKvJ8XXtxdX54vy8uO79-evL0uvtEplDaYWwlpowVcK6lp1TQe2anTdSOCyaZD3KLrOeJMXYKv71vZtI4S3KDlUJ8Xpbt91DD9npORWA21vBhOGmZyVXHIj9X-h5EpxKUWGz_-Bt2GOU36Ek1JvmTUZlTvkYyCK2Lt1HFYQN05wt43O7aJzu-iyf7bfdG5X2B30PqsMXuwBkIexz7_sBzo4w7W1sjocPFDCX3_nIf5wxlZWu8W3727x4frzp6vryr2p_gA_tLM0</recordid><startdate>20040701</startdate><enddate>20040701</enddate><creator>Yen, H-W.</creator><creator>Jakimiuk, A.J.</creator><creator>Munir, I.</creator><creator>Magoffin, D.A.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QP</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20040701</creationdate><title>Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries</title><author>Yen, H-W. ; Jakimiuk, A.J. ; Munir, I. ; Magoffin, D.A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-8a681177abac34a884d9da7395892a0299e0fe1dd6c6454eb5fb7fb911c7e20a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Adult</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>granulosa cell</topic><topic>Granulosa Cells - cytology</topic><topic>Granulosa Cells - metabolism</topic><topic>Humans</topic><topic>Insulin - metabolism</topic><topic>insulin receptor substrate</topic><topic>Insulin Receptor Substrate Proteins</topic><topic>insulin signalling</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>PCOS</topic><topic>Phosphoproteins - metabolism</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Receptor, Insulin - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>theca cell</topic><topic>Theca Cells - cytology</topic><topic>Theca Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yen, H-W.</creatorcontrib><creatorcontrib>Jakimiuk, A.J.</creatorcontrib><creatorcontrib>Munir, I.</creatorcontrib><creatorcontrib>Magoffin, D.A.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular human reproduction</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yen, H-W.</au><au>Jakimiuk, A.J.</au><au>Munir, I.</au><au>Magoffin, D.A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries</atitle><jtitle>Molecular human reproduction</jtitle><addtitle>Mol. Hum. Reprod</addtitle><date>2004-07-01</date><risdate>2004</risdate><volume>10</volume><issue>7</issue><spage>473</spage><epage>479</epage><pages>473-479</pages><issn>1360-9947</issn><issn>1460-2407</issn><eissn>1460-2407</eissn><abstract>The elevated insulin concentrations that occur in many women with polycystic ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism. The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between polycystic ovaries and regular cycling controls. Individual follicles \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((3{\mbox{--}}7{\,}mm)\) \end{document} were obtained from 11 women with PCOS and 10 regularly cycling control women. The theca and granulosa cells were microdissected from each follicle. Total protein was extracted and signalling proteins were measured by western blot analysis. There was no difference in insulin receptor content between PCOS and controls in either theca or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathit{P}{<}0.05),\) \end{document} but IRS-4 was decreased \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathit{P}{<}0.03)\) \end{document} in PCOS theca cells. There were no changes in IRS-1, -2 or -4 in granulosa cells. IRS-3 was undetectable in all samples. There were no changes in phosphatidyl inositol-3 kinase catalytic subunits p110α or p110β in either theca or granulosa cells. These data demonstrate cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>15155816</pmid><doi>10.1093/molehr/gah066</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adaptor Proteins, Signal Transducing Adult Animals Biological and medical sciences Embryology: invertebrates and vertebrates. Teratology Female Fundamental and applied biological sciences. Psychology granulosa cell Granulosa Cells - cytology Granulosa Cells - metabolism Humans Insulin - metabolism insulin receptor substrate Insulin Receptor Substrate Proteins insulin signalling Intracellular Signaling Peptides and Proteins PCOS Phosphoproteins - metabolism Polycystic Ovary Syndrome - metabolism Receptor, Insulin - metabolism Signal Transduction - physiology theca cell Theca Cells - cytology Theca Cells - metabolism |
title | Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries |
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