Regulatory expression of bone morphogenetic protein-6 system in aldosterone production by human adrenocortical cells.
Bone morphogenetic protein-6 (BMP-6) enhances aldosterone production by upregulating angiotensin II (Ang II)-to-MAPK pathway. Here we investigated effects of Ang II and potassium on the BMP system in human adrenocortical H295R cells. BMP-6 transcription was transiently downregulated by treatments with Ang II and potassium. Aldosterone also decreased BMP-6 expression at a high concentration. Chemical inhibitions of transcription and translation abolished the transient reduction of BMP-6, suggesting that destabilization of BMP-6 mRNA was hardly involved while new protein synthesis was possibly mediated in this mechanism. However, BMP-6 protein was stably detected during the exposures of Ang II and potassium. Notably, Ang II, potassium and aldosterone decreased mRNA levels of follistatin that extracellularly neutralizes bioactivities of activins and BMPs although the BMP-6 receptor expression was unaffected. Given the maintenance of bioavailable BMP-6 protein and the receptor expression in adrenocortical cells, endogenous BMP-6 may be a key autocrine modulator for aldosterone production.
Inagaki
Kenichi
K
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, 700-8558, Japan.
Otsuka
Fumio
F
Suzuki
Jiro
J
Otani
Hiroyuki
H
Takeda
Masaya
M
Kano
Yoshihiro
Y
Miyoshi
Tomoko
T
Yamashita
Misuzu
M
Ogura
Toshio
T
Makino
Hirofumi
H
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D038681:Follistatin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D020411:Oligonucleotide Array Sequence Analysis; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D012333:RNA, Messenger; D000804:Angiotensin II; D000450:Aldosterone; D011188:Potassium