Abstract
1α,25-Dihydroxyvitamin D3 (1,25-D3) is critical for the maintenance of normal male reproduction since reduced fertility is observed in vitamin D-deficient rats. Gamma-glutamyl transpeptidase (GGT) is a membrane-bound enzyme that is localized on Sertoli cells and catalyses the transfer of the gamma-glutamyl residues to an amino acid or peptide acceptor. Sertoli cells are also responsible for providing nutrients, as lactate, to the development of germ cells. The aim of this study was to investigate the effect and the mechanism of action of 1,25-D3 on GGT on Sertoli cell functions from 30-day-old immature rat testis. Results demonstrated that 1,25-D3 stimulates GGT activity at Sertoli cells plasma membrane through a PKA-dependent mechanism of action, which was not dependent of active de novo protein synthesis. The hormone increases glucose uptake, as well as lactate production and release by Sertoli cells without altering the reactive oxygen species (ROS) generation. In addition, 1,25-D3 did not change reduced glutathione (GSH) amount or oxygen consumption, and diminished Sertoli cell death. These findings demonstrate that 1,25-D3 stimulatory effect on GGT activity, glucose uptake, LDH activity and lactate production seem to be an important contribution of Sertoli cells for germ cells nutrition and for a full and active ongoing spermatogenesis.
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Abbreviations
- BDC:
-
Bisdemethoxycurcumin
- CM:
-
Curcumin
- 1,25-D3 :
-
1α,25-dihydroxyvitamin D3
- 14C–DG:
-
[U-14C]-2-deoxy-D-glucose
- GGT:
-
Gamma-glutamyl transpeptidase
- KRb:
-
Krebs Ringer-bicarbonate buffer
- LDH:
-
Lactate dehydrogenase
- GSH:
-
Reduced gluthatione
- VDR:
-
Vitamin D receptor
- VDR-AP:
-
Vitamin D alternative pocket
- VDRnuc:
-
Vitamin D nuclear receptor
- VDRmem:
-
Vitamin D membrane receptor
- CH:
-
Cycloheximide
- ST:
-
Stearoylcarnitine chloride
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Acknowledgments
This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico-Brasil (CNPq n° 472071/2013-0) and Coordenação de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Santa Catarina (FAPESC). RG, AR and DLS are registered on the PPG-Biochemistry/UFSC. APZ is registered on the PGFAR/UFSC. FRMBS, AZ and AL are recipient of CNPq productivity fellowship. We thank LAMEB I-CCB/UFSC technicians for their support.
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Gonçalves, R., Zamoner, A., Zanatta, L. et al. 1,25(OH)2 vitamin D3 signalling on immature rat Sertoli cells: gamma-glutamyl transpeptidase and glucose metabolism. J. Cell Commun. Signal. 11, 233–243 (2017). https://doi.org/10.1007/s12079-016-0367-1
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DOI: https://doi.org/10.1007/s12079-016-0367-1