Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons
Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2013/684659 |
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| author | Annamaria Morelli Paolo Comeglio Erica Sarchielli Ilaria Cellai Linda Vignozzi Gabriella B. Vannelli Mario Maggi |
| author_facet | Annamaria Morelli Paolo Comeglio Erica Sarchielli Ilaria Cellai Linda Vignozzi Gabriella B. Vannelli Mario Maggi |
| author_sort | Annamaria Morelli |
| collection | DOAJ |
| description | Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins), along with glucose transporters (GLUT1, GLUT3, and GLUT4). High glucose exposure (22 mM; 40 mM) significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM). Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions. |
| format | Article |
| id | doaj-art-a4542e4437464212bc1a7890d6b27439 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-a4542e4437464212bc1a7890d6b274392025-02-03T06:01:54ZengWileyInternational Journal of Endocrinology1687-83371687-83452013-01-01201310.1155/2013/684659684659Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone NeuronsAnnamaria Morelli0Paolo Comeglio1Erica Sarchielli2Ilaria Cellai3Linda Vignozzi4Gabriella B. Vannelli5Mario Maggi6Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Sexual Medicine and Andrology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, ItalySection of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Sexual Medicine and Andrology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, ItalySection of Sexual Medicine and Andrology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, ItalySection of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Sexual Medicine and Andrology, Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, ItalyMetabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins), along with glucose transporters (GLUT1, GLUT3, and GLUT4). High glucose exposure (22 mM; 40 mM) significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM). Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.http://dx.doi.org/10.1155/2013/684659 |
| spellingShingle | Annamaria Morelli Paolo Comeglio Erica Sarchielli Ilaria Cellai Linda Vignozzi Gabriella B. Vannelli Mario Maggi Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons International Journal of Endocrinology |
| title | Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons |
| title_full | Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons |
| title_fullStr | Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons |
| title_full_unstemmed | Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons |
| title_short | Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons |
| title_sort | negative effects of high glucose exposure in human gonadotropin releasing hormone neurons |
| url | http://dx.doi.org/10.1155/2013/684659 |
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