title: Ghrelin increases growth hormone production and functional expression of NaV1.1 and Na V1.2 channels in pituitary somatotropes.
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.
authors.affiliation: Laboratory of Cell Biology, School of Veterinary Medicine and Animal Science, University of Veracruz, Circunvalación esquina Yáñez s/n, C.P. 91710, Veracruz, Mexico.
authors.forename: Adasue
authors.initials: A
authors.lastname: Magdaleno-Méndez
authors.forename: Belisario
authors.initials: B
authors.lastname: Domínguez
authors.forename: Araceli
authors.initials: A
authors.lastname: Rodríguez-Andrade
authors.forename: Manuel
authors.initials: M
authors.lastname: Barrientos-Morales
authors.forename: Patricia
authors.initials: P
authors.lastname: Cervantes-Acosta
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernández-Beltrán
authors.forename: Ricardo
authors.initials: R
authors.lastname: González-Ramírez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Felix
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D054439:Ghrelin / Q000494:pharmacology*; D013006:Growth Hormone / Q000096:biosynthesis*; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052683:Somatotrophs / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D054439:Ghrelin; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone