AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene
Malnutrition is one of the factors that induces reproductive disorders. However, the underlying biological processes are unclear. AMP-activated protein kinase (AMPK) is an enzyme that plays crucial role as a cellular energy sensor. In the present study, we examined the effects of AMPK activation on...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Society for Reproduction and Development
2019-12-01
|
| Series: | The Journal of Reproduction and Development |
| Subjects: | |
| Online Access: | https://www.jstage.jst.go.jp/article/jrd/66/2/66_2019-143/_pdf/-char/en |
| _version_ | 1827752594944032768 |
|---|---|
| author | Ryutaro MORIYAMA Koichi IWAMOTO Teruki HAGIWARA Saishu YOSHIDA Takako KATO Yukio KATO |
| author_facet | Ryutaro MORIYAMA Koichi IWAMOTO Teruki HAGIWARA Saishu YOSHIDA Takako KATO Yukio KATO |
| author_sort | Ryutaro MORIYAMA |
| collection | DOAJ |
| description | Malnutrition is one of the factors that induces reproductive disorders. However, the underlying biological processes are unclear. AMP-activated protein kinase (AMPK) is an enzyme that plays crucial role as a cellular energy sensor. In the present study, we examined the effects of AMPK activation on the transcription of the murine gonadotropin subunit genes Cga, Lhb, and Fshb, and the gonadotropin-releasing hormone receptor Gnrh-r. Real-time PCR and transcription assay using LβT2 cells demonstrated that 5-amino-imidazole carboxamide riboside (AICAR), a cell-permeable AMP analog, repressed the expression of Lhb. Next, we examined deletion mutants of the upstream region of Lhb and found that the upstream regulatory region of Lhb (–2527 to –2198 b) was responsible for the repression by AICAR. Furthermore, putative transcription factors (SP1, STAT5a, and TEF) that might mediate transcriptional control of the Lhb repression induced by AICAR were identified. In addition, it was confirmed that both AICAR and a competitive inhibitor of glucose metabolism, 2-deoxy-D-glucose, induced AMPK phosphorylation in LβT2 cells. Therefore, the upstream region of Lhb is one of the target sites for glucoprivation inducing AMPK activation. In addition, AMPK plays a role in repressing Lhb expression through the distal –2527 to –2198 b region. |
| first_indexed | 2024-03-11T07:24:28Z |
| format | Article |
| id | doaj.art-66db9f18df8b4974a371f7088cda3378 |
| institution | Directory Open Access Journal |
| issn | 0916-8818 1348-4400 |
| language | English |
| last_indexed | 2024-03-11T07:24:28Z |
| publishDate | 2019-12-01 |
| publisher | The Society for Reproduction and Development |
| record_format | Article |
| series | The Journal of Reproduction and Development |
| spelling | doaj.art-66db9f18df8b4974a371f7088cda33782023-11-17T07:43:30ZengThe Society for Reproduction and DevelopmentThe Journal of Reproduction and Development0916-88181348-44002019-12-016629710410.1262/jrd.2019-143jrdAMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit geneRyutaro MORIYAMA0Koichi IWAMOTO1Teruki HAGIWARA2Saishu YOSHIDA3Takako KATO4Yukio KATO5Laboratory of Environmental Physiology, Department of Life Science, School of Science and Engineering, Kindai University, Osaka 577-8502, JapanLaboratory of Environmental Physiology, Department of Life Science, School of Science and Engineering, Kindai University, Osaka 577-8502, JapanLaboratory of Molecular and Cellular Biology, Department of Life Science, School of Science and Engineering, Kindai University, Osaka 577-8502, JapanDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo 105-8461, JapanLaboratory of Molecular Biology and Gene Regulation, Department of Life Science, School of Agriculture, Meiji University, Kanagawa 214-8571, JapanLaboratory of Molecular Biology and Gene Regulation, Department of Life Science, School of Agriculture, Meiji University, Kanagawa 214-8571, JapanMalnutrition is one of the factors that induces reproductive disorders. However, the underlying biological processes are unclear. AMP-activated protein kinase (AMPK) is an enzyme that plays crucial role as a cellular energy sensor. In the present study, we examined the effects of AMPK activation on the transcription of the murine gonadotropin subunit genes Cga, Lhb, and Fshb, and the gonadotropin-releasing hormone receptor Gnrh-r. Real-time PCR and transcription assay using LβT2 cells demonstrated that 5-amino-imidazole carboxamide riboside (AICAR), a cell-permeable AMP analog, repressed the expression of Lhb. Next, we examined deletion mutants of the upstream region of Lhb and found that the upstream regulatory region of Lhb (–2527 to –2198 b) was responsible for the repression by AICAR. Furthermore, putative transcription factors (SP1, STAT5a, and TEF) that might mediate transcriptional control of the Lhb repression induced by AICAR were identified. In addition, it was confirmed that both AICAR and a competitive inhibitor of glucose metabolism, 2-deoxy-D-glucose, induced AMPK phosphorylation in LβT2 cells. Therefore, the upstream region of Lhb is one of the target sites for glucoprivation inducing AMPK activation. In addition, AMPK plays a role in repressing Lhb expression through the distal –2527 to –2198 b region.https://www.jstage.jst.go.jp/article/jrd/66/2/66_2019-143/_pdf/-char/en5-amino-imidazole carboxamide riboside (aicar)amp-activated protein kinase (ampk)glucoprivationluteinizing hormone (lh)pituitary |
| spellingShingle | Ryutaro MORIYAMA Koichi IWAMOTO Teruki HAGIWARA Saishu YOSHIDA Takako KATO Yukio KATO AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene The Journal of Reproduction and Development 5-amino-imidazole carboxamide riboside (aicar) amp-activated protein kinase (ampk) glucoprivation luteinizing hormone (lh) pituitary |
| title | AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene |
| title_full | AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene |
| title_fullStr | AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene |
| title_full_unstemmed | AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene |
| title_short | AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene |
| title_sort | amp activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β subunit gene |
| topic | 5-amino-imidazole carboxamide riboside (aicar) amp-activated protein kinase (ampk) glucoprivation luteinizing hormone (lh) pituitary |
| url | https://www.jstage.jst.go.jp/article/jrd/66/2/66_2019-143/_pdf/-char/en |
| work_keys_str_mv | AT ryutaromoriyama ampactivatedproteinkinaseactivationreducesthetranscriptionalactivityofthemurineluteinizinghormonebsubunitgene AT koichiiwamoto ampactivatedproteinkinaseactivationreducesthetranscriptionalactivityofthemurineluteinizinghormonebsubunitgene AT terukihagiwara ampactivatedproteinkinaseactivationreducesthetranscriptionalactivityofthemurineluteinizinghormonebsubunitgene AT saishuyoshida ampactivatedproteinkinaseactivationreducesthetranscriptionalactivityofthemurineluteinizinghormonebsubunitgene AT takakokato ampactivatedproteinkinaseactivationreducesthetranscriptionalactivityofthemurineluteinizinghormonebsubunitgene AT yukiokato ampactivatedproteinkinaseactivationreducesthetranscriptionalactivityofthemurineluteinizinghormonebsubunitgene |