Regulatory roles of bone morphogenetic proteins and glucocorticoids in catecholamine production by rat pheochromocytoma cells

Yoshihiro Kano, Fumio Otsuka, Masaya Takeda, Jiro Suzuki, Kenichi Inagaki, Tomoko Miyoshi, Manabu Miyamoto, Hiroyuki Otani, Toshio Ogura, Hirofumi Makino

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

Original languageEnglish
Pages (from-to)5332-5340
Number of pages9
JournalEndocrinology
Volume146
Issue number12
DOIs
Publication statusPublished - Dec 2005

Fingerprint

Bone Morphogenetic Proteins
Pheochromocytoma
Activins
Glucocorticoids
Catecholamines
Dexamethasone
PC12 Cells
Activin Receptors
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 2
Dopamine
Dihydroxyphenylalanine
Carboxy-Lyases
Tyrosine 3-Monooxygenase
Ligands
Type I Bone Morphogenetic Protein Receptors
Phosphorylation
Inhibins
p38 Mitogen-Activated Protein Kinases
Epinephrine

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Regulatory roles of bone morphogenetic proteins and glucocorticoids in catecholamine production by rat pheochromocytoma cells. / Kano, Yoshihiro; Otsuka, Fumio; Takeda, Masaya; Suzuki, Jiro; Inagaki, Kenichi; Miyoshi, Tomoko; Miyamoto, Manabu; Otani, Hiroyuki; Ogura, Toshio; Makino, Hirofumi.

In: Endocrinology, Vol. 146, No. 12, 12.2005, p. 5332-5340.

Research output: Contribution to journalArticle

Kano, Yoshihiro ; Otsuka, Fumio ; Takeda, Masaya ; Suzuki, Jiro ; Inagaki, Kenichi ; Miyoshi, Tomoko ; Miyamoto, Manabu ; Otani, Hiroyuki ; Ogura, Toshio ; Makino, Hirofumi. / Regulatory roles of bone morphogenetic proteins and glucocorticoids in catecholamine production by rat pheochromocytoma cells. In: Endocrinology. 2005 ; Vol. 146, No. 12. pp. 5332-5340.
@article{f4bebf26e10f4a879eb40013e16e63ed,
title = "Regulatory roles of bone morphogenetic proteins and glucocorticoids in catecholamine production by rat pheochromocytoma cells",
abstract = "We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.",
author = "Yoshihiro Kano and Fumio Otsuka and Masaya Takeda and Jiro Suzuki and Kenichi Inagaki and Tomoko Miyoshi and Manabu Miyamoto and Hiroyuki Otani and Toshio Ogura and Hirofumi Makino",
year = "2005",
month = "12",
doi = "10.1210/en.2005-0474",
language = "English",
volume = "146",
pages = "5332--5340",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "12",

}

TY - JOUR

T1 - Regulatory roles of bone morphogenetic proteins and glucocorticoids in catecholamine production by rat pheochromocytoma cells

AU - Kano, Yoshihiro

AU - Otsuka, Fumio

AU - Takeda, Masaya

AU - Suzuki, Jiro

AU - Inagaki, Kenichi

AU - Miyoshi, Tomoko

AU - Miyamoto, Manabu

AU - Otani, Hiroyuki

AU - Ogura, Toshio

AU - Makino, Hirofumi

PY - 2005/12

Y1 - 2005/12

N2 - We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

AB - We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

UR - http://www.scopus.com/inward/record.url?scp=27844470592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27844470592&partnerID=8YFLogxK

U2 - 10.1210/en.2005-0474

DO - 10.1210/en.2005-0474

M3 - Article

C2 - 16150914

AN - SCOPUS:27844470592

VL - 146

SP - 5332

EP - 5340

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 12

ER -