Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promoters
Activin, GnRH, and estrogen are key endocrine inputs known to regulate the GnRH receptor (GnRHR) promoter; however, it has become increasingly evident that the mechanisms regulating the GnRHR promoter vary by model and species. To explore these differences, transgenic mice harboring either a wild-ty...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1597028/full |
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| author | Christianne Magee Jennifer E. Kouri Brian D. Cherrington Jeremy D. Cantlon Dilyara A. Murtazina Todd A. Farmerie Meredith H. Davidsen Terry M. Nett Colin M. Clay |
| author_facet | Christianne Magee Jennifer E. Kouri Brian D. Cherrington Jeremy D. Cantlon Dilyara A. Murtazina Todd A. Farmerie Meredith H. Davidsen Terry M. Nett Colin M. Clay |
| author_sort | Christianne Magee |
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| description | Activin, GnRH, and estrogen are key endocrine inputs known to regulate the GnRH receptor (GnRHR) promoter; however, it has become increasingly evident that the mechanisms regulating the GnRHR promoter vary by model and species. To explore these differences, transgenic mice harboring either a wild-type mouse GnRHR (mGnRHR) or sheep (oGnRHR) GnRHR promoter fused to luciferase (-LUC) were infected with an adenovirus overexpressing follistatin, neutralizing activin and decreasing serum concentrations of FSH in both animal models. However, follistatin overexpression in the oGnRHR-LUC mouse more than doubled luciferase expression, whereas in the mGnRHR-LUC animals it led to a 40% decrease in luciferase expression. Thus, the divergent transcriptional responses of the mouse and sheep GnRHR genes to activin appear to be reliably recapitulated in transgenic mice. To further elucidate mechanisms regulating oGnRHR expression, a mouse with a mutated cyclic AMP response element (µCRE) in the proximal oGnRHR-LUC promoter was developed. Using an electrophoretic mobility shift assay, a specific and high affinity interaction of the ovine CRE with nuclear components exists, but these are not modified in the presence of E2, indicating that CRE binding protein (CREB) is necessary but not sufficient to mediate E2 input to oGnRHR expression. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-2eeb2ea8a70546c5bce890313e5e83132025-08-20T03:34:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.15970281597028Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promotersChristianne Magee0Jennifer E. Kouri1Brian D. Cherrington2Jeremy D. Cantlon3Dilyara A. Murtazina4Todd A. Farmerie5Meredith H. Davidsen6Terry M. Nett7Colin M. Clay8Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesCollege of Agriculture, Life Sciences, and Natural Resources, Department of Zoology and Physiology, University of Wyoming, Laramie, WY, United StatesAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesAnimal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesActivin, GnRH, and estrogen are key endocrine inputs known to regulate the GnRH receptor (GnRHR) promoter; however, it has become increasingly evident that the mechanisms regulating the GnRHR promoter vary by model and species. To explore these differences, transgenic mice harboring either a wild-type mouse GnRHR (mGnRHR) or sheep (oGnRHR) GnRHR promoter fused to luciferase (-LUC) were infected with an adenovirus overexpressing follistatin, neutralizing activin and decreasing serum concentrations of FSH in both animal models. However, follistatin overexpression in the oGnRHR-LUC mouse more than doubled luciferase expression, whereas in the mGnRHR-LUC animals it led to a 40% decrease in luciferase expression. Thus, the divergent transcriptional responses of the mouse and sheep GnRHR genes to activin appear to be reliably recapitulated in transgenic mice. To further elucidate mechanisms regulating oGnRHR expression, a mouse with a mutated cyclic AMP response element (µCRE) in the proximal oGnRHR-LUC promoter was developed. Using an electrophoretic mobility shift assay, a specific and high affinity interaction of the ovine CRE with nuclear components exists, but these are not modified in the presence of E2, indicating that CRE binding protein (CREB) is necessary but not sufficient to mediate E2 input to oGnRHR expression.https://www.frontiersin.org/articles/10.3389/fendo.2025.1597028/fullGnRH receptoractivinestrogen gene expressiontransgenic micefollistatin |
| spellingShingle | Christianne Magee Jennifer E. Kouri Brian D. Cherrington Jeremy D. Cantlon Dilyara A. Murtazina Todd A. Farmerie Meredith H. Davidsen Terry M. Nett Colin M. Clay Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promoters Frontiers in Endocrinology GnRH receptor activin estrogen gene expression transgenic mice follistatin |
| title | Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promoters |
| title_full | Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promoters |
| title_fullStr | Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promoters |
| title_full_unstemmed | Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promoters |
| title_short | Evidence for divergent endocrine regulation of the murine and ovine GnRH receptor gene promoters |
| title_sort | evidence for divergent endocrine regulation of the murine and ovine gnrh receptor gene promoters |
| topic | GnRH receptor activin estrogen gene expression transgenic mice follistatin |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1597028/full |
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