PMID- 19342457
OWN - NLM
STAT- MEDLINE
DCOM- 20090724
LR  - 20211020
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 7
DP  - 2009 Jul
TI  - Regulation of aldosterone and cortisol production by the transcriptional 
      repressor neuron restrictive silencer factor.
PG  - 3110-7
LID - 10.1210/en.2008-1624 [doi]
AB  - Aldosterone synthase (CYP11B2) and 11 beta-hydroxylase (CYP11B1) regulate 
      aldosterone and cortisol production, respectively. The expression of these 
      enzymes is promoted by calcium influx through Cav3.2, a T-type calcium channel. 
      Neuron-restrictive silencer factor (NRSF) binds to neuron-restrictive silencer 
      element (NRSE) to suppress the transcription of NRSE-containing genes. We found a 
      NRSE-like sequence in human CYP11B2 and CYP11B1 genes as well as the CACNA1H gene 
      of many mammalian species. The CACNA1H gene encodes the alpha-subunit of Cav3.2. 
      Here we investigated how NRSF/NRSE regulates aldosterone and cortisol synthesis. 
      Inhibition of endogenous NRSF by an adenovirus-expressing dominant-negative NRSF 
      (AD/dnNRSF) increased human CYP11B2 and CYP11B1 mRNA expression, leading to 
      aldosterone and cortisol secretion in human adrenocortical (H295R) cells. In 
      reporter gene experiments, NRSE suppressed luciferase reporters driven by CYP11B2 
      and CYP11B1 promoters and dnNRSF enhanced them. Moreover, cotransfection of 
      dnNRSF increased luciferase activity of reporter genes after deletion or mutation 
      of NRSE, suggesting that NRSF/NRSE regulates transcription of CYP11B2 and CYP11B1 
      genes indirectly. AD/dnNRSF augmented mRNA expression of rat CYP11B2 and CYP11B1 
      genes, neither of which contains a NRSE-like sequence in rat adrenal cells. 
      AD/dnNRSE also significantly increased CACNA1H mRNA in H295R and rat adrenal 
      cells. Efonidipine, a T/L-type calcium channel blocker, significantly suppressed 
      dnNRSF-mediated up-regulation of CYP11B2 and CYP11B1 expression. Moreover, 
      NRSF/NRSE is also involved in angiotensin II- and K(+)-stimulated augmentation of 
      CYP11B2 and CYP11B1 gene transcription. In conclusion, NRSF/NRSE controls 
      aldosterone and cortisol synthesis by regulating CYP11B2 and CYP11B1 gene 
      transcription mainly through NRSF/NRSE-mediated enhancement of the CACNA1H gene.
FAU - Somekawa, Satoshi
AU  - Somekawa S
AD  - The First Department of Internal Medicine, Nara Medical University, 840 
      Shijo-cho, Kashihara, Nara 634, Japan.
FAU - Imagawa, Keiichi
AU  - Imagawa K
FAU - Naya, Noriyuki
AU  - Naya N
FAU - Takemoto, Yasuhiro
AU  - Takemoto Y
FAU - Onoue, Kenji
AU  - Onoue K
FAU - Okayama, Satoshi
AU  - Okayama S
FAU - Takeda, Yukiji
AU  - Takeda Y
FAU - Kawata, Hiroyuki
AU  - Kawata H
FAU - Horii, Manabu
AU  - Horii M
FAU - Nakajima, Tamio
AU  - Nakajima T
FAU - Uemura, Shiro
AU  - Uemura S
FAU - Mochizuki, Naoki
AU  - Mochizuki N
FAU - Saito, Yoshihiko
AU  - Saito Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090402
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (CACNA1H protein, human)
RN  - 0 (Calcium Channels, T-Type)
RN  - 0 (RE1-silencing transcription factor)
RN  - 0 (Repressor Proteins)
RN  - 11128-99-7 (Angiotensin II)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 1.14.15.4 (Cytochrome P-450 CYP11B2)
RN  - EC 1.14.15.4 (Steroid 11-beta-Hydroxylase)
RN  - RWP5GA015D (Potassium)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Aldosterone/*biosynthesis
MH  - Angiotensin II/physiology
MH  - Animals
MH  - Calcium Channels, T-Type/genetics
MH  - Cell Line
MH  - Cytochrome P-450 CYP11B2/genetics/metabolism
MH  - Humans
MH  - Hydrocortisone/*biosynthesis
MH  - Potassium/physiology
MH  - Rats
MH  - Repressor Proteins/*physiology
MH  - Steroid 11-beta-Hydroxylase/genetics
PMC - PMC2703558
EDAT- 2009/04/04 09:00
MHDA- 2009/07/25 09:00
PMCR- 2010/07/01
CRDT- 2009/04/04 09:00
PHST- 2009/04/04 09:00 [entrez]
PHST- 2009/04/04 09:00 [pubmed]
PHST- 2009/07/25 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - en.2008-1624 [pii]
AID - 4849 [pii]
AID - 10.1210/en.2008-1624 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Jul;150(7):3110-7. doi: 10.1210/en.2008-1624. Epub 2009 Apr 
      2.