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Article

Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway

  • Authors:
    • Xiaocen Chang
    • Yuyan Zhao
    • Shujing Ju
    • Lei Guo
  • View Affiliations / Copyright

    Affiliations: Departments of Endocrinology and Orthopedic Surgery, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 1523-1528
    |
    Published online on: October 6, 2014
       https://doi.org/10.3892/ijmm.2014.1959
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Abstract

Orexin-A is a regulatory peptide involved in the regulation of food intake, sleep-wakefulness, and it has various endocrine and metabolic functions. It orchestrates diverse central and peripheral processes through the stimulation of two G-protein coupled receptors, orexin receptor type 1 (OX1 receptor) and orexin receptor type 2 (OX2 receptor). In this study, human adrenocortical cells (NCI-H295R cells) were incubated with various concentrations of orexin-A (10-10 to 10-6 M) in vitro, and the mRNA and protein expression of OX1 receptor was determined in the cells. In addition, NCI-H295R cells treated with 10-6 M orexin-A were then treated with or without OX1 receptor specific antagonist (SB334867), AKT antagonist (PF-04691502), or a combination of both. Subsequently, cell proliferation, the cortisol content in the medium and the mRNA and protein expression expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) were analyzed. The activity of the AKT signaling pathway was also determined in the NCI-H295R cells. We observed that the increase in the mRNA and protein expression of OX1 receptor was orexin-A concentration-dependent, with 10-6 M orexin-A exerting the most potent effect. Orexin-A enhanced cell proliferation and cortisol production, and increased the mRNA and protein expression of 3β-HSD in the NCI-H295R cells; however, these effects were partly blocked by the OX1 receptor antagonist, the AKT antagonist and the combination of both. Furthermore, orexin-A significantly increased the phosphorylation of AKT, with the levels of total AKT protein remaining unaltered. This effect was blocked in the presence of PF-04691502 (10-6 M), SB334867 (10-6 M) and the combination of both. On the whole, our data demonstrate that the effects of orexin-A on the survival and function of human adrenocortical cells are mediated through the AKT signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Chang X, Zhao Y, Ju S and Guo L: Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway. Int J Mol Med 34: 1523-1528, 2014.
APA
Chang, X., Zhao, Y., Ju, S., & Guo, L. (2014). Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway. International Journal of Molecular Medicine, 34, 1523-1528. https://doi.org/10.3892/ijmm.2014.1959
MLA
Chang, X., Zhao, Y., Ju, S., Guo, L."Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway". International Journal of Molecular Medicine 34.6 (2014): 1523-1528.
Chicago
Chang, X., Zhao, Y., Ju, S., Guo, L."Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway". International Journal of Molecular Medicine 34, no. 6 (2014): 1523-1528. https://doi.org/10.3892/ijmm.2014.1959
Copy and paste a formatted citation
x
Spandidos Publications style
Chang X, Zhao Y, Ju S and Guo L: Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway. Int J Mol Med 34: 1523-1528, 2014.
APA
Chang, X., Zhao, Y., Ju, S., & Guo, L. (2014). Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway. International Journal of Molecular Medicine, 34, 1523-1528. https://doi.org/10.3892/ijmm.2014.1959
MLA
Chang, X., Zhao, Y., Ju, S., Guo, L."Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway". International Journal of Molecular Medicine 34.6 (2014): 1523-1528.
Chicago
Chang, X., Zhao, Y., Ju, S., Guo, L."Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway". International Journal of Molecular Medicine 34, no. 6 (2014): 1523-1528. https://doi.org/10.3892/ijmm.2014.1959
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