PMID- 24265455
OWN - NLM
STAT- MEDLINE
DCOM- 20140320
LR  - 20211021
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 155
IP  - 2
DP  - 2014 Feb
TI  - Synergistic activation of steroidogenic acute regulatory protein expression and 
      steroid biosynthesis by retinoids: involvement of cAMP/PKA signaling.
PG  - 576-91
LID - 10.1210/en.2013-1694 [doi]
AB  - Both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the 
      action of retinoids that play important roles in reproductive development and 
      function, as well as steroidogenesis. Regulation of steroid biosynthesis is 
      principally mediated by the steroidogenic acute regulatory protein (StAR); 
      however, the modes of action of retinoids in the regulation of steroidogenesis 
      remain obscure. In this study we demonstrate that all-trans retinoic acid (atRA) 
      enhances StAR expression, but not its phosphorylation (P-StAR), and progesterone 
      production in MA-10 mouse Leydig cells. Activation of the protein kinase A (PKA) 
      cascade, by dibutyrl-cAMP or type I/II PKA analogs, markedly increased 
      retinoid-responsive StAR, P-StAR, and steroid levels. Targeted silencing of 
      endogenous RARalpha and RXRalpha, with small interfering RNAs, resulted in decreases in 
      9-cis RA-stimulated StAR and progesterone levels. Truncation of and mutational 
      alterations in the 5'-flanking region of the StAR gene demonstrated the 
      importance of the -254/-1-bp region in retinoid responsiveness. An 
      oligonucleotide probe encompassing an RXR/liver X receptor recognition motif, 
      located within the -254/-1-bp region, specifically bound MA-10 nuclear proteins 
      and in vitro transcribed/translated RXRalpha and RARalpha in EMSAs. Transcription of the 
      StAR gene in response to atRA and dibutyrl-cAMP was influenced by several 
      factors, its up-regulation being dependent on phosphorylation of cAMP 
      response-element binding protein (CREB). Chromatin immunoprecipitation studies 
      revealed the association of phosphorylation of CREB, CREB binding protein, RXRalpha, 
      and RARalpha to the StAR promoter. Further studies elucidated that hormone-sensitive 
      lipase plays an important role in atRA-mediated regulation of the steroidogenic 
      response that involves liver X receptor signaling. These findings delineate the 
      molecular events by which retinoids influence cAMP/PKA signaling and provide 
      additional and novel insight into the regulation of StAR expression and 
      steroidogenesis in mouse Leydig cells.
FAU - Manna, Pulak R
AU  - Manna PR
AD  - Department of Cell Biology and Biochemistry (P.R.M., S.R.K., D.M.S.), Department 
      of Dermatology and Pathology (C.L.S.), Texas Tech University Health Sciences 
      Center, Lubbock, Texas 79430; and Department of Pathology and Laboratory Medicine 
      (A.T.S.), University of Tennessee Health Science Center, Memphis, Tennessee 
      38163.
FAU - Slominski, Andrzej T
AU  - Slominski AT
FAU - King, Steven R
AU  - King SR
FAU - Stetson, Cloyce L
AU  - Stetson CL
FAU - Stocco, Douglas M
AU  - Stocco DM
LA  - eng
GR  - R01 HD017481/HD/NICHD NIH HHS/United States
GR  - R37 HD017481/HD/NICHD NIH HHS/United States
GR  - HD-17481/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131121
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Steroids)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bucladesine/pharmacology
MH  - Cyclic AMP/genetics/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism
MH  - Leydig Cells/cytology/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/drug effects
MH  - Receptors, Retinoic Acid/genetics/metabolism
MH  - Retinoid X Receptors/genetics/metabolism
MH  - Retinoids/genetics/*metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Steroids/*biosynthesis
MH  - Up-Regulation/drug effects/physiology
PMC - PMC3891939
EDAT- 2013/11/23 06:00
MHDA- 2014/03/22 06:00
PMCR- 2015/02/01
CRDT- 2013/11/23 06:00
PHST- 2013/11/23 06:00 [entrez]
PHST- 2013/11/23 06:00 [pubmed]
PHST- 2014/03/22 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - en.2013-1694 [pii]
AID - EN-13-1694 [pii]
AID - 10.1210/en.2013-1694 [doi]
PST - ppublish
SO  - Endocrinology. 2014 Feb;155(2):576-91. doi: 10.1210/en.2013-1694. Epub 2013 Nov 
      21.