PMID- 20420936
OWN - NLM
STAT- MEDLINE
DCOM- 20101018
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1801
IP  - 9
DP  - 2010 Sep
TI  - 1alpha,25-Dihydroxyvitamin D3 affects hormone production and expression of 
      steroidogenic enzymes in human adrenocortical NCI-H295R cells.
PG  - 1056-62
LID - 10.1016/j.bbalip.2010.04.009 [doi]
AB  - The current study presents data indicating that 1alpha,25-dihydroxyvitamin D(3) 
      affects the production of hormones and expression of crucial steroidogenic 
      enzymes in the human adrenocortical cell line NCI-H295R. This cell line is widely 
      used as a model for adrenal steroidogenesis. Treatment of the cells with 
      1alpha,25-dihydroxyvitamin D(3) suppressed the levels of corticosterone, 
      aldosterone, DHEA, DHEA-sulfate and androstenedione in the culture medium. In 
      order to study the mechanisms behind this suppression of hormone production, we 
      investigated the effects of 1alpha,25-dihydroxyvitamin D(3) on important genes 
      and enzymes controlling the biosynthesis of adrenal hormones. The mRNA levels 
      were decreased for CYP21A2 while they were increased for CYP11A1 and CYP17A1. No 
      significant changes were observed in mRNA for CYP11B1, CYP11B2 or 
      3beta-hydroxysteroid dehydrogenase (3betaHSD). In similarity with the effects on 
      mRNA levels, also the endogenous enzyme activity of CYP21A2 decreased after 
      treatment with 1alpha,25-dihydroxyvitamin D(3). Interestingly, the two 
      CYP17A1-mediated activities were influenced reciprocally - the 
      17alpha-hydroxylase activity increased whereas the 17,20-lyase activity 
      decreased. The current data indicate that the 1alpha,25-dihydroxyvitamin 
      D(3)-mediated decrease in corticosterone and androgen production is due to 
      suppression of the 21-hydroxylase activity by CYP21A2 and the 17,20-lyase 
      activity by CYP17A1, respectively. In conclusion, the current study reports novel 
      findings on 1alpha,25-dihydroxyvitamin D(3)-mediated effects on hormone 
      production and regulation of genes and enzymes involved in steroidogenesis in the 
      adrenocortical NCI-H295R cell line, a model for human adrenal cortex.
CI  - 2010 Elsevier B.V. All rights reserved.
FAU - Lundqvist, Johan
AU  - Lundqvist J
AD  - Department of Pharmaceutical Biosciences, Division of Biochemistry, Box 578, 
      University of Uppsala, SE-75123 Uppsala, Sweden.
FAU - Norlin, Maria
AU  - Norlin M
FAU - Wikvall, Kjell
AU  - Wikvall K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100424
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Calcium Channel Agonists)
RN  - 0 (Hormones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Steroids)
RN  - 409J2J96VR (Androstenedione)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 4964P6T9RB (Aldosterone)
RN  - 57B09Q7FJR (Dehydroepiandrosterone Sulfate)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
RN  - EC 1.14.14.16 (CYP21A2 protein, human)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
RN  - EC 1.14.14.19 (CYP17A1 protein, human)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
RN  - EC 1.14.15.4 (Cytochrome P-450 CYP11B2)
RN  - EC 1.14.15.4 (Steroid 11-beta-Hydroxylase)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
RN  - FXC9231JVH (Calcitriol)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 3-Hydroxysteroid Dehydrogenases/genetics/metabolism
MH  - Adrenal Cortex/*drug effects/*metabolism
MH  - Aldosterone/metabolism
MH  - Androstenedione/metabolism
MH  - Blotting, Western
MH  - Calcitriol/*pharmacology
MH  - Calcium Channel Agonists/*pharmacology
MH  - Cells, Cultured/drug effects/enzymology
MH  - Cholesterol Side-Chain Cleavage Enzyme/genetics/metabolism
MH  - Corticosterone/metabolism
MH  - Cytochrome P-450 CYP11B2/genetics/metabolism
MH  - Dehydroepiandrosterone/metabolism
MH  - Dehydroepiandrosterone Sulfate/metabolism
MH  - Hormones/*metabolism
MH  - Humans
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Steroid 11-beta-Hydroxylase/genetics/metabolism
MH  - Steroid 17-alpha-Hydroxylase/genetics/*metabolism
MH  - Steroid 21-Hydroxylase/genetics/*metabolism
MH  - Steroids/metabolism
EDAT- 2010/04/28 06:00
MHDA- 2010/10/19 06:00
CRDT- 2010/04/28 06:00
PHST- 2009/12/22 00:00 [received]
PHST- 2010/03/05 00:00 [revised]
PHST- 2010/04/12 00:00 [accepted]
PHST- 2010/04/28 06:00 [entrez]
PHST- 2010/04/28 06:00 [pubmed]
PHST- 2010/10/19 06:00 [medline]
AID - S1388-1981(10)00088-0 [pii]
AID - 10.1016/j.bbalip.2010.04.009 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2010 Sep;1801(9):1056-62. doi: 
      10.1016/j.bbalip.2010.04.009. Epub 2010 Apr 24.