G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope
Gonadotropin-releasing hormone (GnRH) acts at gonadotropes to direct the synthesis of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The frequency of GnRH pulses determines the pattern of gonadotropin synthesis. Several hypotheses for how the gonadotrope decodes...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 2012-06, Vol.287 (25), p.21550-21560 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 21560 |
|---|---|
| container_issue | 25 |
| container_start_page | 21550 |
| container_title | The Journal of biological chemistry |
| container_volume | 287 |
| creator | Choi, Soon-Gang Jia, Jingjing Pfeffer, Robert L. Sealfon, Stuart C. |
| description | Gonadotropin-releasing hormone (GnRH) acts at gonadotropes to direct the synthesis of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The frequency of GnRH pulses determines the pattern of gonadotropin synthesis. Several hypotheses for how the gonadotrope decodes GnRH frequency to regulate gonadotropin subunit genes differentially have been proposed. However, key regulators and underlying mechanisms remain uncertain. We investigated the role of individual G proteins by perturbations using siRNA or bacterial toxins. In LβT2 gonadotrope cells, FSHβ gene induction depended predominantly on Gαq/11, whereas LHβ expression depended on Gαs. Specifically reducing Gαs signaling also disinhibited FSHβ expression, suggesting the presence of a Gαs-dependent signal that suppressed FSH biosynthesis. The presence of secreted factors influencing FSHβ expression levels was tested by studying the effects of conditioned media from Gαs knockdown and cholera toxin-treated cells on FSHβ expression. These studies and related Transwell culture experiments implicate Gαs-dependent secreted factors in regulating both FSHβ and LHβ gene expression. siRNA studies identify inhibinα as a Gαs-dependent GnRH-induced autocrine regulatory factor that contributes to feedback suppression of FSHβ expression. These results uncover differential regulation of the gonadotropin genes by Gαq/11 and by Gαs and implicate autocrine and gonadotrope-gonadotrope paracrine regulatory loops in the differential induction of gonadotropin genes.
The mechanism for differential control of gonadotropin gene induction by GnRH is not established.
GnRH activates Gαs and Gαq/11, which modulate LH and FSH synthesis, respectively, by a mechanism including secreted factors.
Different G proteins and autocrine signaling regulate the pattern of FSH and LH expression by GnRH.
A novel G protein and autocrine signaling mechanism has been identified. |
| doi_str_mv | 10.1074/jbc.M112.348607 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3375576</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925820498461</els_id><sourcerecordid>1021126114</sourcerecordid><originalsourceid>FETCH-LOGICAL-c509t-77a246ab7caebdf8647b7ad0371b48634f56c93c575ad918266a73c9b1b48ad13</originalsourceid><addsrcrecordid>eNp1kU1v1DAQhi0EotvCmRvykUu2dhzHyQWpKu0WqahVCxI3y7Eny1RZe7Gdiv77erWlKgd8GcnzzDsfLyEfOFtypprju8Euv3FeL0XTtUy9IgvOOlEJyX--JgvGal71tewOyGFKd6y8pudvyUFdy6ZXPVuQtKLXMWRAn6jxjp7MOdiIHugtrr2Z0K_pFxxHiOAzmml6oDewnieTga6CNy7kGLbo6e08zB4zPfuzjZASBk_L7zXmGbOJDy9geEfejGZK8P4pHpEf52ffTy-qy6vV19OTy8pK1udKKVM3rRmUNTC4sWsbNSjjmFB8KNuKZpSt7YWVShrX865uW6OE7Ydd2jgujsjnve52HjbgbNkgmklvI27KRDoY1P9mPP7S63CvhVBSqrYIfHoSiOH3DCnrDSYL02Q8hDlpXu7L65bzpqDHe9TGkFKE8bkNZ3pnlS5W6Z1Vem9Vqfj4crpn_q83Bej3AJQb3SNEnSyCt-Awgs3aBfyv-CMrXqZ1</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1021126114</pqid></control><display><type>article</type><title>G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Choi, Soon-Gang ; Jia, Jingjing ; Pfeffer, Robert L. ; Sealfon, Stuart C.</creator><creatorcontrib>Choi, Soon-Gang ; Jia, Jingjing ; Pfeffer, Robert L. ; Sealfon, Stuart C.</creatorcontrib><description>Gonadotropin-releasing hormone (GnRH) acts at gonadotropes to direct the synthesis of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The frequency of GnRH pulses determines the pattern of gonadotropin synthesis. Several hypotheses for how the gonadotrope decodes GnRH frequency to regulate gonadotropin subunit genes differentially have been proposed. However, key regulators and underlying mechanisms remain uncertain. We investigated the role of individual G proteins by perturbations using siRNA or bacterial toxins. In LβT2 gonadotrope cells, FSHβ gene induction depended predominantly on Gαq/11, whereas LHβ expression depended on Gαs. Specifically reducing Gαs signaling also disinhibited FSHβ expression, suggesting the presence of a Gαs-dependent signal that suppressed FSH biosynthesis. The presence of secreted factors influencing FSHβ expression levels was tested by studying the effects of conditioned media from Gαs knockdown and cholera toxin-treated cells on FSHβ expression. These studies and related Transwell culture experiments implicate Gαs-dependent secreted factors in regulating both FSHβ and LHβ gene expression. siRNA studies identify inhibinα as a Gαs-dependent GnRH-induced autocrine regulatory factor that contributes to feedback suppression of FSHβ expression. These results uncover differential regulation of the gonadotropin genes by Gαq/11 and by Gαs and implicate autocrine and gonadotrope-gonadotrope paracrine regulatory loops in the differential induction of gonadotropin genes.
The mechanism for differential control of gonadotropin gene induction by GnRH is not established.
GnRH activates Gαs and Gαq/11, which modulate LH and FSH synthesis, respectively, by a mechanism including secreted factors.
Different G proteins and autocrine signaling regulate the pattern of FSH and LH expression by GnRH.
A novel G protein and autocrine signaling mechanism has been identified.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M112.348607</identifier><identifier>PMID: 22549790</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Autocrine ; Autocrine Communication - physiology ; Cell Line ; Cell Signaling ; Follicle Stimulating Hormone - genetics ; Follicle Stimulating Hormone - metabolism ; G Protein-coupled Receptors (GPCRs) ; G Proteins ; Gene Expression Regulation - physiology ; Gene Regulation ; Gonadotrope ; Gonadotropin ; Gonadotropin-Releasing Hormone ; Gonadotropins - genetics ; Gonadotropins - metabolism ; GTP-Binding Proteins - genetics ; GTP-Binding Proteins - metabolism ; Luteinizing Hormone - genetics ; Luteinizing Hormone - metabolism ; Mice ; Paracrine ; Pituitary Gland - metabolism ; Signaling Circuit ; siRNA</subject><ispartof>The Journal of biological chemistry, 2012-06, Vol.287 (25), p.21550-21560</ispartof><rights>2012 © 2012 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2012 by The American Society for Biochemistry and Molecular Biology, Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-77a246ab7caebdf8647b7ad0371b48634f56c93c575ad918266a73c9b1b48ad13</citedby><cites>FETCH-LOGICAL-c509t-77a246ab7caebdf8647b7ad0371b48634f56c93c575ad918266a73c9b1b48ad13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375576/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375576/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22549790$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Soon-Gang</creatorcontrib><creatorcontrib>Jia, Jingjing</creatorcontrib><creatorcontrib>Pfeffer, Robert L.</creatorcontrib><creatorcontrib>Sealfon, Stuart C.</creatorcontrib><title>G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Gonadotropin-releasing hormone (GnRH) acts at gonadotropes to direct the synthesis of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The frequency of GnRH pulses determines the pattern of gonadotropin synthesis. Several hypotheses for how the gonadotrope decodes GnRH frequency to regulate gonadotropin subunit genes differentially have been proposed. However, key regulators and underlying mechanisms remain uncertain. We investigated the role of individual G proteins by perturbations using siRNA or bacterial toxins. In LβT2 gonadotrope cells, FSHβ gene induction depended predominantly on Gαq/11, whereas LHβ expression depended on Gαs. Specifically reducing Gαs signaling also disinhibited FSHβ expression, suggesting the presence of a Gαs-dependent signal that suppressed FSH biosynthesis. The presence of secreted factors influencing FSHβ expression levels was tested by studying the effects of conditioned media from Gαs knockdown and cholera toxin-treated cells on FSHβ expression. These studies and related Transwell culture experiments implicate Gαs-dependent secreted factors in regulating both FSHβ and LHβ gene expression. siRNA studies identify inhibinα as a Gαs-dependent GnRH-induced autocrine regulatory factor that contributes to feedback suppression of FSHβ expression. These results uncover differential regulation of the gonadotropin genes by Gαq/11 and by Gαs and implicate autocrine and gonadotrope-gonadotrope paracrine regulatory loops in the differential induction of gonadotropin genes.
The mechanism for differential control of gonadotropin gene induction by GnRH is not established.
GnRH activates Gαs and Gαq/11, which modulate LH and FSH synthesis, respectively, by a mechanism including secreted factors.
Different G proteins and autocrine signaling regulate the pattern of FSH and LH expression by GnRH.
A novel G protein and autocrine signaling mechanism has been identified.</description><subject>Animals</subject><subject>Autocrine</subject><subject>Autocrine Communication - physiology</subject><subject>Cell Line</subject><subject>Cell Signaling</subject><subject>Follicle Stimulating Hormone - genetics</subject><subject>Follicle Stimulating Hormone - metabolism</subject><subject>G Protein-coupled Receptors (GPCRs)</subject><subject>G Proteins</subject><subject>Gene Expression Regulation - physiology</subject><subject>Gene Regulation</subject><subject>Gonadotrope</subject><subject>Gonadotropin</subject><subject>Gonadotropin-Releasing Hormone</subject><subject>Gonadotropins - genetics</subject><subject>Gonadotropins - metabolism</subject><subject>GTP-Binding Proteins - genetics</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Luteinizing Hormone - genetics</subject><subject>Luteinizing Hormone - metabolism</subject><subject>Mice</subject><subject>Paracrine</subject><subject>Pituitary Gland - metabolism</subject><subject>Signaling Circuit</subject><subject>siRNA</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1v1DAQhi0EotvCmRvykUu2dhzHyQWpKu0WqahVCxI3y7Eny1RZe7Gdiv77erWlKgd8GcnzzDsfLyEfOFtypprju8Euv3FeL0XTtUy9IgvOOlEJyX--JgvGal71tewOyGFKd6y8pudvyUFdy6ZXPVuQtKLXMWRAn6jxjp7MOdiIHugtrr2Z0K_pFxxHiOAzmml6oDewnieTga6CNy7kGLbo6e08zB4zPfuzjZASBk_L7zXmGbOJDy9geEfejGZK8P4pHpEf52ffTy-qy6vV19OTy8pK1udKKVM3rRmUNTC4sWsbNSjjmFB8KNuKZpSt7YWVShrX865uW6OE7Ydd2jgujsjnve52HjbgbNkgmklvI27KRDoY1P9mPP7S63CvhVBSqrYIfHoSiOH3DCnrDSYL02Q8hDlpXu7L65bzpqDHe9TGkFKE8bkNZ3pnlS5W6Z1Vem9Vqfj4crpn_q83Bej3AJQb3SNEnSyCt-Awgs3aBfyv-CMrXqZ1</recordid><startdate>20120615</startdate><enddate>20120615</enddate><creator>Choi, Soon-Gang</creator><creator>Jia, Jingjing</creator><creator>Pfeffer, Robert L.</creator><creator>Sealfon, Stuart C.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120615</creationdate><title>G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope</title><author>Choi, Soon-Gang ; Jia, Jingjing ; Pfeffer, Robert L. ; Sealfon, Stuart C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-77a246ab7caebdf8647b7ad0371b48634f56c93c575ad918266a73c9b1b48ad13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Autocrine</topic><topic>Autocrine Communication - physiology</topic><topic>Cell Line</topic><topic>Cell Signaling</topic><topic>Follicle Stimulating Hormone - genetics</topic><topic>Follicle Stimulating Hormone - metabolism</topic><topic>G Protein-coupled Receptors (GPCRs)</topic><topic>G Proteins</topic><topic>Gene Expression Regulation - physiology</topic><topic>Gene Regulation</topic><topic>Gonadotrope</topic><topic>Gonadotropin</topic><topic>Gonadotropin-Releasing Hormone</topic><topic>Gonadotropins - genetics</topic><topic>Gonadotropins - metabolism</topic><topic>GTP-Binding Proteins - genetics</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Luteinizing Hormone - genetics</topic><topic>Luteinizing Hormone - metabolism</topic><topic>Mice</topic><topic>Paracrine</topic><topic>Pituitary Gland - metabolism</topic><topic>Signaling Circuit</topic><topic>siRNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Soon-Gang</creatorcontrib><creatorcontrib>Jia, Jingjing</creatorcontrib><creatorcontrib>Pfeffer, Robert L.</creatorcontrib><creatorcontrib>Sealfon, Stuart C.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Soon-Gang</au><au>Jia, Jingjing</au><au>Pfeffer, Robert L.</au><au>Sealfon, Stuart C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2012-06-15</date><risdate>2012</risdate><volume>287</volume><issue>25</issue><spage>21550</spage><epage>21560</epage><pages>21550-21560</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Gonadotropin-releasing hormone (GnRH) acts at gonadotropes to direct the synthesis of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The frequency of GnRH pulses determines the pattern of gonadotropin synthesis. Several hypotheses for how the gonadotrope decodes GnRH frequency to regulate gonadotropin subunit genes differentially have been proposed. However, key regulators and underlying mechanisms remain uncertain. We investigated the role of individual G proteins by perturbations using siRNA or bacterial toxins. In LβT2 gonadotrope cells, FSHβ gene induction depended predominantly on Gαq/11, whereas LHβ expression depended on Gαs. Specifically reducing Gαs signaling also disinhibited FSHβ expression, suggesting the presence of a Gαs-dependent signal that suppressed FSH biosynthesis. The presence of secreted factors influencing FSHβ expression levels was tested by studying the effects of conditioned media from Gαs knockdown and cholera toxin-treated cells on FSHβ expression. These studies and related Transwell culture experiments implicate Gαs-dependent secreted factors in regulating both FSHβ and LHβ gene expression. siRNA studies identify inhibinα as a Gαs-dependent GnRH-induced autocrine regulatory factor that contributes to feedback suppression of FSHβ expression. These results uncover differential regulation of the gonadotropin genes by Gαq/11 and by Gαs and implicate autocrine and gonadotrope-gonadotrope paracrine regulatory loops in the differential induction of gonadotropin genes.
The mechanism for differential control of gonadotropin gene induction by GnRH is not established.
GnRH activates Gαs and Gαq/11, which modulate LH and FSH synthesis, respectively, by a mechanism including secreted factors.
Different G proteins and autocrine signaling regulate the pattern of FSH and LH expression by GnRH.
A novel G protein and autocrine signaling mechanism has been identified.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22549790</pmid><doi>10.1074/jbc.M112.348607</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 2012-06, Vol.287 (25), p.21550-21560 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3375576 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Autocrine Autocrine Communication - physiology Cell Line Cell Signaling Follicle Stimulating Hormone - genetics Follicle Stimulating Hormone - metabolism G Protein-coupled Receptors (GPCRs) G Proteins Gene Expression Regulation - physiology Gene Regulation Gonadotrope Gonadotropin Gonadotropin-Releasing Hormone Gonadotropins - genetics Gonadotropins - metabolism GTP-Binding Proteins - genetics GTP-Binding Proteins - metabolism Luteinizing Hormone - genetics Luteinizing Hormone - metabolism Mice Paracrine Pituitary Gland - metabolism Signaling Circuit siRNA |
| title | G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T03%3A27%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=G%20Proteins%20and%20Autocrine%20Signaling%20Differentially%20Regulate%20Gonadotropin%20Subunit%20Expression%20in%20Pituitary%20Gonadotrope&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Choi,%20Soon-Gang&rft.date=2012-06-15&rft.volume=287&rft.issue=25&rft.spage=21550&rft.epage=21560&rft.pages=21550-21560&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M112.348607&rft_dat=%3Cproquest_pubme%3E1021126114%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1021126114&rft_id=info:pmid/22549790&rft_els_id=S0021925820498461&rfr_iscdi=true |