title: Identification of adrenal genes regulated in a potassium-dependent manner.
abstract: Potassium and angiotensin II are the main stimulators of aldosterone secretion from the adrenal cortex. As potassium-induced in vivo gene regulation in the adrenal cortex has not been studied in detail, we applied a stepwise screening approach: first, we investigated the effects of chronic potassium substitution in mice. Microarray analysis of adrenal glands revealed a set of genes (set A) that were counter-regulated in a high potassium (HP) and low potassium substitution group, while others (set B) were highly upregulated in the HP intake group. In a second step, time dependency of expression changes of these pre-defined genes was studied following short-term potassium stimulation experiments in vivo. Thirdly, dose dependency of potassium-induced gene regulation was investigated in vitro. Finally, to provide indirect evidence for the potential relevance of the detected changes for autonomous aldosterone secretion, expression analysis of aldosterone-producing adenomas was compared with normal adrenal glands. While most investigated genes were similarly regulated following long- and short-term potassium stimulation in vivo, observed changes were reproducible in NCI h295R adrenocortical cells mostly for the set of genes identified in the HP group (set B). Similarly, in Conn's adenomas, mostly genes from set B displayed changes in expression pattern in comparison to normal adrenal glands, while genes from set A were mostly unchanged. Thus, while in vivo models can help in identifying genes potentially involved in potassium-dependent aldosterone secretion, these findings also underline the necessity to interpret potassium-induced gene regulation on the basis of the experimental setting.
authors.affiliation: Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians-University, Ziemssenstrasse 1, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dierks
authors.forename: Urs D
authors.initials: UD
authors.lastname: Lichtenauer
authors.forename: Simone
authors.initials: S
authors.lastname: Sackmann
authors.forename: Ariadni
authors.initials: A
authors.lastname: Spyroglou
authors.forename: Igor
authors.initials: I
authors.lastname: Shapiro
authors.forename: Marcel
authors.initials: M
authors.lastname: Geyer
authors.forename: Jenny
authors.initials: J
authors.lastname: Manonopoulou
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
authors.forename: Constanze
authors.initials: C
authors.lastname: Hantel
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
mesh_terms: D000236:Adenoma / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011188:Potassium / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D011188:Potassium