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Ghrelin increases growth hormone production and functional expression of NaV1.1 and NaV1.2 channels in pituitary somatotropes

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Abstract

A variety of ion channels are expressed in the plasma membrane of somatotropes within the anterior pituitary gland. Modification of these channels is linked to intracellular Ca2+ levels and therefore to hormone secretion. Previous investigations have shown that the gut-derived orexigenic peptide hormone ghrelin and synthetic GH-releasing peptides (GHRPs) stimulate release of growth hormone (GH) and increase the number of functional voltage-gated Ca2+ and Na+ channels in the membrane of clonal GC somatotropes. Here, we reveal that chronic treatment with ghrelin and its synthetic analog GHRP-6 also increases GH release from bovine pituitary somatotropes in culture, and that this action is associated with a significant increase in Na+ macroscopic current. Consistent with this, Na+ current blockade with tetrodotoxin (TTX) abolished the ghrelin- and GHRP-6-induced increase in GH release. Furthermore, semi-quantitative and real-time RT-PCR analysis revealed an upregulation in the transcript levels of GH, as well as of NaV1.1 and NaV1.2, two isoforms of TTX-sensitive Na+ channels expressed in somatotropes, after treatment with ghrelin or GHRP-6. These findings improve our knowledge on (i) the cellular mechanisms involved in the control of GH secretion, (ii) the molecular diversity of Na+ channels in pituitary somatotropes, and (iii) the regulation of GH and Na+ channel gene expression by ghrelin and GHRPs.

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Acknowledgments

This work was partially supported by grants (128707 and 104264) from National Council of Science and Technology (Conacyt, Mexico) to R.F. and B.D., respectively. We thank to the two anonymous reviewers that provided sound guidance and suggestions.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Cell Biology, School of Veterinary Medicine and Animal Science, University of Veracruz, Circunvalación esquina Yáñez s/n, C.P. 91710, Veracruz, Mexico

    Adasue Magdaleno-Méndez & Belisario Domínguez

  2. Department of Chemistry and Biochemistry, Veracruz Institute of Technology, Veracruz, Mexico

    Araceli Rodríguez-Andrade

  3. Laboratory of Reproduction Biology, School of Veterinary Medicine and Animal Science, University of Veracruz, Veracruz, Mexico

    Manuel Barrientos-Morales

  4. Laboratory of Molecular Biology, School of Veterinary Medicine and Animal Science, University of Veracruz, Veracruz, Mexico

    Patricia Cervantes-Acosta

  5. Laboratory of Functional Alterations, School of Veterinary Medicine and Animal Science, University of Veracruz, Veracruz, Mexico

    Antonio Hernández-Beltrán

  6. Department of Molecular Biology and Histocompatibility, “Dr. Manuel Gea González” General Hospital, Mexico City, Mexico

    Ricardo González-Ramírez

  7. Department of Cell Biology, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, Mexico

    Ricardo Felix

  8. Departamento de Biología Celular, Cinvestav-IPN, Avenida IPN 2508, Col. Zacatenco, CP 07360, México, DF, Mexico

    Ricardo Felix

Authors
  1. Adasue Magdaleno-Méndez
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  2. Belisario Domínguez
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  3. Araceli Rodríguez-Andrade
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  4. Manuel Barrientos-Morales
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  5. Patricia Cervantes-Acosta
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  6. Antonio Hernández-Beltrán
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  7. Ricardo González-Ramírez
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  8. Ricardo Felix
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Corresponding authors

Correspondence to Belisario Domínguez or Ricardo Felix.

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Magdaleno-Méndez, A., Domínguez, B., Rodríguez-Andrade, A. et al. Ghrelin increases growth hormone production and functional expression of NaV1.1 and NaV1.2 channels in pituitary somatotropes. Endocrine 48, 929–936 (2015). https://doi.org/10.1007/s12020-014-0392-x

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  • DOI: https://doi.org/10.1007/s12020-014-0392-x

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