Dexamethasone increases potassium channel messenger RNA and activity in clonal pituitary cells.
Glucocorticoid hormones are released as part of the stress response and regulate secretion by the pituitary. Since the activity of ion channels also influences secretion, we examined the effect of the glucocorticoid agonist dexamethasone on ion channel expression. K+ channel mRNA was detected in rat hypothalamus and anterior pituitary, with probes derived from the rat Kv1 gene, a member of the mammalian voltage-gated K+ channel superfamily. High levels were also detected in PRL-secreting clonal (GH3 and GH4C1) rat pituitary cells. Dexamethasone rapidly increased the steady state concentration of Kv1 mRNA in GH3 cells in a dose-dependent manner. This change in gene expression was accompanied by an increase in whole cell voltage-gated K+ current [lk(i)] with similar pharmacology to the Kv1 gene product. Our findings indicate that hormones may act directly on excitable cells to produce long term effects on electrical activity and secretion by regulating K+ channel expression.
Levitan
E S
ES
Department of Pharmacology, Yale University, New Haven, Connecticut 06510.
Hemmick
L M
LM
Birnberg
N C
NC
Kaczmarek
L K
LK
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011188:Potassium / Q000493:pharmacokinetics; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D015221:Potassium Channels; D012333:RNA, Messenger; D003907:Dexamethasone; D011388:Prolactin; D011188:Potassium