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The in vitro regulation of growth hormone secretion by orexins

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Abstract

Orexins, orexigenic neuropeptides, have recently been discovered in lateral hypothalamus and play an important role in the regulation of pituitary hormone secretion. Two subtypes of orexin receptors (orexin-1 and orexin-2) have been demonstrated in pituitaries. In this experiment, the effects of orexins on voltage-gated Ca2+ currents and the GH release in primary cultured ovine somatotropes were examined. Voltage-gated Ca2+ currents were isolated in ovine somatotropes as L, T, and N currents using whole-cell patch-clamp techniques and specific Ca2+ channel blocker and toxin. Application of orexin-A or orexin-B (100 nM) significantly, dose-depen-dently, and reversibly increased only nifedipine-sensitive L-type Ca2+ current. Inhibitors of PKC (calphostin C, PKC inhibitory peptide) but not inhibitors of PKA (H89, PKA inhibitory peptide) cancelled the increase in the L current by orexins. Co-administration of orexin-A and GHRH (10 nM) showed an additive effect on the L current. Specific intracellular Ca2+-store-depleting reagent, thapsigargin (1 µM), did not affect the orexin-induced increase in the L current. Orexin-B alone slightly increased GH release and co-administration of orexin-A and GHRH synergistically stimulated GH secretion in vitro. It is therefore suggested that orexins may play an important role in regulating GHRH-stimulated GH secretion through an increase in the L-type Ca2+ current and the PKC-mediated signaling pathways in ovine somatotropes.

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Authors and Affiliations

  1. Prince Henry’s Institute of Medical Research, and Department of Physiology, Monash University, Clayton, Victoria, Australia

    Chen Chen & Ruwei Xu

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  1. Chen Chen
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Correspondence to Chen Chen.

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Chen, C., Xu, R. The in vitro regulation of growth hormone secretion by orexins. Endocr 22, 57–66 (2003). https://doi.org/10.1385/ENDO:22:1:57

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  • DOI: https://doi.org/10.1385/ENDO:22:1:57

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