Abstract
Melatonin is functionally involved in the control of circadian rhythm and hormonal secretion. In the present study, we investigated the roles of melatonin in the interaction of catecholamine synthesis with adrenocortical steroids by focusing on bone morphogenetic protein (BMP)-4 expressed in the adrenal medulla using rat pheochromocytoma PC12 cells. Melatonin treatment significantly reduced the mRNA expression of catecholamine synthases, including the rate-limiting enzyme tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanine decarboxylase and dopamine-β-hydroxylase expressed in PC12 cells. In accordance with changes in the expression levels of enzymes, dopamine production and cAMP synthesis determined in the culture medium and cell lysate were also suppressed by melatonin. The MT1 receptor, but not the MT2 receptor, was expressed in PC12 cells, and luzindole treatment reversed the inhibitory effect of melatonin on Th expression, suggesting that MT1 is a functional receptor for the control of catecholamine synthesis. Interestingly, melatonin enhanced the inhibitory effect of BMP-4 on Th mRNA expression in PC12 cells. Melatonin treatment accelerated BMP-4-induced phosphorylation of SMAD1/5/8 and transcription of the BMP target gene Id1. Of note, melatonin significantly upregulated Alk2 and Bmpr2 mRNA levels but suppressed inhibitory Smad6/7 expression, leading to the enhancement of SMAD1/5/8 signaling in PC12 cells, while BMP-4 did not affect Mt1 expression. Regarding the interaction with adrenocortical steroids, melatonin preferentially enhanced glucocorticoid-induced Th mRNA through upregulation of the glucocorticoid receptor and downregulation of Bmp4 expression, whereas melatonin repressed Th mRNA expression induced by aldosterone or androgen without affecting expression levels of the receptors for mineralocorticoid and androgen. Collectively, the results indicate that melatonin plays a modulatory role in catecholamine synthesis by cooperating with BMP-4 and glucocorticoid in the adrenal medulla.
| Original language | English |
|---|---|
| Pages (from-to) | 182-189 |
| Number of pages | 8 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 165 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- Bone morphogenetic protein
- Catecholamine
- Glucocorticoid
- Melatonin
- PC12
- Pheochromocytoma
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Medicine(all)
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Endocrinology
- Clinical Biochemistry
- Cell Biology
Cite this
Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions. / Komatsubara, Motoshi; Hara, Takayuki; Hosoya, Takeshi; Toma, Kishio; Tsukamoto-Yamauchi, Naoko; Iwata, Nahoko; Inagaki, Kenichi; Wada, Jun; Otsuka, Fumio.
In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 165, 01.01.2017, p. 182-189.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions
AU - Komatsubara, Motoshi
AU - Hara, Takayuki
AU - Hosoya, Takeshi
AU - Toma, Kishio
AU - Tsukamoto-Yamauchi, Naoko
AU - Iwata, Nahoko
AU - Inagaki, Kenichi
AU - Wada, Jun
AU - Otsuka, Fumio
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Melatonin is functionally involved in the control of circadian rhythm and hormonal secretion. In the present study, we investigated the roles of melatonin in the interaction of catecholamine synthesis with adrenocortical steroids by focusing on bone morphogenetic protein (BMP)-4 expressed in the adrenal medulla using rat pheochromocytoma PC12 cells. Melatonin treatment significantly reduced the mRNA expression of catecholamine synthases, including the rate-limiting enzyme tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanine decarboxylase and dopamine-β-hydroxylase expressed in PC12 cells. In accordance with changes in the expression levels of enzymes, dopamine production and cAMP synthesis determined in the culture medium and cell lysate were also suppressed by melatonin. The MT1 receptor, but not the MT2 receptor, was expressed in PC12 cells, and luzindole treatment reversed the inhibitory effect of melatonin on Th expression, suggesting that MT1 is a functional receptor for the control of catecholamine synthesis. Interestingly, melatonin enhanced the inhibitory effect of BMP-4 on Th mRNA expression in PC12 cells. Melatonin treatment accelerated BMP-4-induced phosphorylation of SMAD1/5/8 and transcription of the BMP target gene Id1. Of note, melatonin significantly upregulated Alk2 and Bmpr2 mRNA levels but suppressed inhibitory Smad6/7 expression, leading to the enhancement of SMAD1/5/8 signaling in PC12 cells, while BMP-4 did not affect Mt1 expression. Regarding the interaction with adrenocortical steroids, melatonin preferentially enhanced glucocorticoid-induced Th mRNA through upregulation of the glucocorticoid receptor and downregulation of Bmp4 expression, whereas melatonin repressed Th mRNA expression induced by aldosterone or androgen without affecting expression levels of the receptors for mineralocorticoid and androgen. Collectively, the results indicate that melatonin plays a modulatory role in catecholamine synthesis by cooperating with BMP-4 and glucocorticoid in the adrenal medulla.
AB - Melatonin is functionally involved in the control of circadian rhythm and hormonal secretion. In the present study, we investigated the roles of melatonin in the interaction of catecholamine synthesis with adrenocortical steroids by focusing on bone morphogenetic protein (BMP)-4 expressed in the adrenal medulla using rat pheochromocytoma PC12 cells. Melatonin treatment significantly reduced the mRNA expression of catecholamine synthases, including the rate-limiting enzyme tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanine decarboxylase and dopamine-β-hydroxylase expressed in PC12 cells. In accordance with changes in the expression levels of enzymes, dopamine production and cAMP synthesis determined in the culture medium and cell lysate were also suppressed by melatonin. The MT1 receptor, but not the MT2 receptor, was expressed in PC12 cells, and luzindole treatment reversed the inhibitory effect of melatonin on Th expression, suggesting that MT1 is a functional receptor for the control of catecholamine synthesis. Interestingly, melatonin enhanced the inhibitory effect of BMP-4 on Th mRNA expression in PC12 cells. Melatonin treatment accelerated BMP-4-induced phosphorylation of SMAD1/5/8 and transcription of the BMP target gene Id1. Of note, melatonin significantly upregulated Alk2 and Bmpr2 mRNA levels but suppressed inhibitory Smad6/7 expression, leading to the enhancement of SMAD1/5/8 signaling in PC12 cells, while BMP-4 did not affect Mt1 expression. Regarding the interaction with adrenocortical steroids, melatonin preferentially enhanced glucocorticoid-induced Th mRNA through upregulation of the glucocorticoid receptor and downregulation of Bmp4 expression, whereas melatonin repressed Th mRNA expression induced by aldosterone or androgen without affecting expression levels of the receptors for mineralocorticoid and androgen. Collectively, the results indicate that melatonin plays a modulatory role in catecholamine synthesis by cooperating with BMP-4 and glucocorticoid in the adrenal medulla.
KW - Bone morphogenetic protein
KW - Catecholamine
KW - Glucocorticoid
KW - Melatonin
KW - PC12
KW - Pheochromocytoma
UR - http://www.scopus.com/inward/record.url?scp=85000578306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85000578306&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2016.06.002
DO - 10.1016/j.jsbmb.2016.06.002
M3 - Article
C2 - 27267863
AN - SCOPUS:85000578306
VL - 165
SP - 182
EP - 189
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
ER -