{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:24Z","timestamp":1792806144187,"version":"4.5.0"},"reference-count":31,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3]]},"abstract":"\n OBJECTIVE<\/jats:title>\n \n Prior profiling of the human pituitary adenoma (PA) DNA methylome showed the potassium channel subunit\u2013encoding gene\n KCNAB2<\/jats:italic>\n to be highly differentially methylated between nonfunctional PAs (NFPAs) and growth hormone (GH)\u2013secreting PAs, with greater\n KCNAB2<\/jats:italic>\n methylation detected in secretory PAs.\n KCNAB2<\/jats:italic>\n encodes an aldo-keto reductase that, among other things, negatively regulates members of the voltage-gated potassium channel (K\n v<\/jats:sub>\n ) family. In this study, the authors aimed to determine whether modulation of Kcnab2 expression would alter GH secretion in the GH3 mammosomatotroph rat cell line. In addition, they examined whether dosing GH3 cells with the antiarrhythmic drug quinidine, a known inhibitor of K\n v<\/jats:sub>\n and voltage-gated sodium channels, would affect hormonal secretion.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Previously generated RNA-seq data were reanalyzed to compare\n KCNAB2<\/jats:italic>\n expression levels in human NFPAs and GH-secreting PAs. Kcnab2 was overexpressed in GH3 cells using plasmid transfection and knocked down using shRNA, with confirmation by quantitative polymerase chain reaction (qPCR). GH concentrations in cell culture supernatants collected 24 hours after cell seeding were measured using enzyme-linked immunosorbent assay (ELISA). Separately, quinidine was administered to GH3 cells at graduated doses. GH and prolactin concentrations in supernatants collected 48 hours after quinidine treatment were measured by fluorometric immunoassay.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Modulation of expression at the transcript level in GH3 cells resulted in proportionate changes in the expression of GH mRNA and secretion of GH peptide, as confirmed by qPCR and ELISA. Specifically, partial knockdown of\n Kcnab2<\/jats:italic>\n was associated with fewer GH RNA transcripts and less GH secretion compared with controls, while augmentation of\n Kcnab2<\/jats:italic>\n expression was associated with more GH transcripts and secretion than the controls. Administration of quinidine (\u2265 50 \u00b5M) reduced both GH and prolactin secretion in a dose-dependent fashion (p \u2264 0.05).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n \n GH secretion in a somatotroph cell line is partially dependent on\n KCNAB2<\/jats:italic>\n gene expression and may be mitigated in vitro by quinidine. These results collectively suggest a potential new target and pharmacological candidate to be considered in the development of clinical therapeutics for acromegaly.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2019.12.jns192435","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T09:52:16Z","timestamp":1583488336000},"page":"787-793","source":"Crossref","is-referenced-by-count":13,"title":["Role of KCNAB2 expression in modulating hormone secretion in somatotroph pituitary adenoma"],"prefix":"10.3171","volume":"134","author":[{"given":"Charles","family":"Ashton","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhn K.","family":"Rhie","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Carmichael","sequence":"additional","affiliation":[{"name":"Medicine (Division of Endocrinology), Keck School of Medicine, University of Southern California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Zada","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Endocr Rev","first-page":"2","article-title":"POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease","volume":"22","author":"Andersen B","year":"2001","unstructured":"Andersen B, Rosenfeld MG: POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. 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