Uncarboxylated Osteocalcin Stimulates 25-Hydroxy Vitamin D Production in Leydig Cell Line Through a GPRC6a-Dependent Pathway
| Autor: | Simone Tescari, Vincenzo De Filippis, Luca De Toni, Roberto Vettor, Marco Ferigo, Alberto Ferlin, Angelo Avogaro, Carlo Foresta, Valentina Scattolini |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Osteocalcin GPRC6A Biology Gene Expression Regulation Enzymologic Cell Line Receptors G-Protein-Coupled Human chorionic gonadotropin Bone remodeling Mice Endocrinology Internal medicine medicine Vitamin D and neurology Animals Humans Vitamin D Receptor News and Views Testosterone Leydig cell Leydig Cells Carbon Dioxide Middle Aged medicine.anatomical_structure Case-Control Studies biology.protein Cholestanetriol 26-Monooxygenase Metabolic Networks and Pathways |
| Zdroj: | Endocrinology. 155:4266-4274 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2014-1283 |
| Popis: | Recent studies disclosed a cross talk between testis and bone. By the action of LH, Leydig cells are able to modulate bone metabolism through testosterone and insulin-like factor 3. Moreover, LH modulates the Leydig expression of CYP2R1, the key enzyme involved in vitamin D (Vit D) 25-hydroxylation. However, pathways regulating CYP2R1 expression have been poorly investigated. The cross talk from the bone to the testis of the vitamin D 25-hydroxylase CYP2R1 involves osteocalcin (OC), which is produced by the osteoblasts and stimulates the production of testosterone by the Leydig cells through its putative receptor GPRC6A, a cation-sensing G-protein-coupled receptor. The aim of this study was to investigate the possible action of OC on CYP2R1 expression and 25-hydroxy Vit D (25-OH Vit D) production in a mouse Leydig cell line (MA-10). After confirmation of the expression of GPRC6A by MA-10, we found that stimulation with either human chorionic gonadotropin or uncarboxylated-OC (ucOC) increases CYP2R1 protein expression in a dose-dependent manner and, in turn, increases the release of 25-OH Vit D in culture medium. This effect was abolished by receptor blockade with, respectively, anti-LH receptor and anti-GPRC6A antibodies. Moreover, both agonists converged to phosphorylation of Erk1/2 by a likely differential action on second messengers. Human chorionic gonadotropin induced slow “tonic” increase of intercellular calcium and accumulation of cAMP, whereas ucOC mainly induced phasic increase of cell calcium. Supporting these findings, we found that serum ucOC positively correlated with 25-OH Vit D levels in 40 overweight male patients and 21 controls. Altogether, our results suggest that OC contributes with LH to 25-OH Vit D production by Leydig cells. |
| Databáze: | OpenAIRE |
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