RRC ID 34907
Author Tani Y, Yamada S, Inoshita N, Hirata Y, Shichiri M.
Title Regulation of growth hormone secretion by (pro)renin receptor.
Journal Sci Rep
Abstract (Pro)renin receptor (PRR) has a single transmembrane domain that co-purifies with the vacuolar H(+)-ATPase (V-ATPase). In addition to its role in cellular acidification, V-ATPase has been implicated in membrane fusion and exocytosis via its Vo domain. Results from the present study show that PRR is expressed in pituitary adenoma cells and regulates growth hormone (GH) release via V-ATPase-induced cellular acidification. Positive PRR immunoreactivity was detected more often in surgically resected, growth hormone-producing adenomas (GHomas) than in nonfunctional pituitary adenomas. GHomas strongly expressing PRR showed excess GH secretion, as evidenced by distinctly high plasma GH and insulin-like growth factor-1 levels, as well as an elevated nadir GH in response to the oral glucose tolerance test. Suppression of PRR expression in rat GHoma-derived GH3 cells using PRR siRNA resulted in reduced GH secretion and significantly enhanced intracellular GH accumulation. GH3 treatment with bafilomycin A1, a V-ATPase inhibitor, also blocked GH release, indicating mediation via impaired cellular acidification of V-ATPase. PRR knockdown decreased Atp6l, a subunit of the Vo domain that destabilizes V-ATPase assembly, increased intracellular GH, and decreased GH release. To our knowledge, this is the first report demonstrating a pivotal role for PRR in a pituitary hormone release mechanism.
Volume 5
Pages 10878
Published 2015-6-3
DOI 10.1038/srep10878
PII srep10878
PMID 26039928
PMC PMC4454151
MeSH Animals Cell Line, Tumor Enzyme Stability Female Gene Expression Human Growth Hormone / blood Human Growth Hormone / metabolism* Humans Hydrogen-Ion Concentration Insulin-Like Growth Factor I / metabolism Intracellular Space / metabolism Kruppel-Like Transcription Factors / metabolism Male Middle Aged Pituitary Neoplasms / genetics Pituitary Neoplasms / metabolism Pituitary Neoplasms / pathology Promyelocytic Leukemia Zinc Finger Protein Protein Transport RNA, Small Interfering / genetics Rats Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism* Renin / metabolism Signal Transduction Vacuolar Proton-Translocating ATPases / genetics Vacuolar Proton-Translocating ATPases / metabolism*
IF 3.998
Times Cited 8
DNA material pcDNA3.1_rPLZF (RDB13479)