MON-009 GLUT1-Mediated Glycolysis Facilitates GnRH-Induced Secretion of Luteinizing Hormone
| Autor: | Mark A. Lawson, Dequina A. Nicholas, Vashti S. Knight, Olivia Molinar-Inglis, Karen J. Tonsfeldt, Pamela L. Mellon, JoAnn Trejo, Tomohiro Terasaka, Shannon B. Z. Stephens, Alexander S. Kauffman |
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| Rok vydání: | 2020 |
| Předmět: |
endocrine system
medicine.medical_specialty medicine.drug_class 1.1 Normal biological development and functioning Endocrinology Diabetes and Metabolism Glucose uptake Stimulation Biology Gonadotropic cell Underpinning research Internal medicine medicine Reproductive Endocrinology Contraception/Reproduction Diabetes Neurosciences Glucose transporter Female Reproduction: Basic Mechanisms Endocrinology biology.protein GLUT1 Gonadotropin Luteinizing hormone AcademicSubjects/MED00250 hormones hormone substitutes and hormone antagonists Hormone |
| Zdroj: | Journal of the Endocrine Society, vol 4, iss Supplement_1 Journal of the Endocrine Society Journal of the Endocrine Society, vol 4, iss Suppl 1 |
| ISSN: | 2472-1972 |
| DOI: | 10.1210/jendso/bvaa046.1694 |
| Popis: | Author(s): Nicholas, Dequina; Knight, Vashti; Tonsfeldt, Karen; Terasaka, Tomohiro; Molinar-Inglis, Olivia; Stephens, Shannon Brooke Zoe; Trejo, Joann; Kauffman, Alexander S; Mellon, Pamela L; Lawson, Mark A | Abstract: Abstract Reproduction requires intensive energy expenditure, and energy availability impacts the function of the reproductive endocrine HPG-axis. Accordingly, the reproductive axis is suppressed during hypoglycemia. Circulating blood glucose can directly interact with gonadotropes within the highly vascular pituitary. Therefore, it is possible that gonadotropes may sense energy availability via the presence of glucose in the circulation and integrate this status with input from GnRH neurons to regulate hormone production. Gonadotropes dominantly express glucose transporter 1 (GLUT1) and increase glucose uptake in response to GnRH. Thus, we hypothesized that gonadotropes engage glycolysis in response to GnRH stimulation due to the high energy demand of protein synthesis required for LH production. We developed an approach to sort and successfully culture primary gonadotropes from wild type mice. Using this approach, we performed extracellular flux analysis and found that gonadotropes respond to GnRH by inducing GLUT1-mediated glycolysis that is independent of mitochondrial respiration. Knock-down of GLUT1 expression in the LβT2 gonadotrope cell line, glucose restriction, or treatment with the competitive inhibitor of glycolysis, 2-DG, diminished GnRH-induced LH secretion, indicating GLUT1 expression is necessary for maximal GnRH-induced LH secretion. We confirmed this observation in primary female mouse gonadotropes by limiting glucose availability which resulted in diminished basal LH and FSH secretion. Lastly, GLUT1 expression in the pituitary correlates with GnRH receptor expression and is increased during the LH surge in a mouse model. These results implicate glucose uptake through GLUT1 as permissive for gonadotrope secretion of LH and therefore reproductive function, especially the LH surge. We conclude that GLUT1-mediated glucose uptake is an important rate-limiting step in gonadotropin synthesis and operation of the HPG-axis. |
| Databáze: | OpenAIRE |
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