PMID- 12768545
OWN - NLM
STAT- MEDLINE
DCOM- 20030723
LR  - 20161124
IS  - 1059-910X (Print)
IS  - 1059-910X (Linking)
VI  - 61
IP  - 3
DP  - 2003 Jun 15
TI  - ACTH modulation of transcription factors responsible for steroid hydroxylase gene 
      expression in the adrenal cortex.
PG  - 300-7
AB  - Steroid hormone biosynthesis in the adrenal cortex and gonads involves the 
      coordinated transcription of the genes encoding the steroid hydroxylases, 
      3beta-hydroxysteroid dehydrogenase (3betaHSD), the steroidogenic acute regulatory 
      protein (StAR), and adrenodoxin (Adx). Transcriptional regulation of 
      steroidogenic genes is multifactorial, entailing developmental, tissue-specific, 
      constitutive, and cAMP-dependent mechanisms. Optimal steroidogenic capacity is 
      achieved by the actions of ACTH which exerts transcriptional pressure on all 
      steroidogenic genes. The actions of ACTH in the adrenal cortex have been studied 
      in great detail and is mediated by cAMP and protein kinase A (PKA) via two 
      temporally distinct pathways. The acute response leads to mobilization of 
      cholesterol, the initial substrate for all steroidogenic pathways, from cellular 
      stores to the inner mitochondrial membrane where cholesterol sidechain cleavage 
      cytochrome P450 (P45011A1) resides. The slower, chronic response of ACTH in the 
      adrenal cortex directs transcription of the genes encoding the steroidogenic 
      enzymes. Although steroidogenic gene transcription in response to ACTH is 
      cAMP-dependent, the consensus cAMP response pathway (CRE/CREB) is not involved. 
      Instead, each steroidogenic gene utilizes unique cAMP-responsive sequences (CRS) 
      found in the promoters of each gene, which bind a diverse array of transcription 
      factors. Moreover, once specific transcription factors are bound to the promoters 
      of the steroidogenic genes, increased gene expression requires posttranslational 
      modification (phosphorylation/dephosphorylation) of the transcription factors and 
      binding of coactivator proteins. This review provides a general view (with 
      emphasis on the human) of the important factors involved in regulating 
      steroidogenic gene expression and ultimately steroid hormone biosynthesis.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Sewer, Marion B
AU  - Sewer MB
AD  - Department of Biochemistry and Center in Toxicology, Vanderbilt University School 
      of Medicine, Nashville, TN 37232-0146, USA. marion.sewer@biology.gatech.edu
FAU - Waterman, Michael R
AU  - Waterman MR
LA  - eng
GR  - DK 28350/DK/NIDDK NIH HHS/United States
GR  - ES 00267/ES/NIEHS NIH HHS/United States
GR  - T32 CA 09582/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Microsc Res Tech
JT  - Microscopy research and technique
JID - 9203012
RN  - 0 (Phosphoproteins)
RN  - 0 (Transcription Factors)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 12687-22-8 (Adrenodoxin)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
RN  - EC 1.14.15.4 (Steroid 11-beta-Hydroxylase)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
SB  - IM
MH  - Adrenal Cortex/*metabolism
MH  - Adrenocorticotropic Hormone/*pharmacology
MH  - Adrenodoxin/genetics
MH  - Animals
MH  - Cholesterol Side-Chain Cleavage Enzyme/genetics
MH  - Cyclic AMP/physiology
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Phosphoproteins/genetics
MH  - Protein Processing, Post-Translational
MH  - Steroid 11-beta-Hydroxylase/genetics
MH  - Steroid 17-alpha-Hydroxylase/genetics
MH  - Steroid Hydroxylases/*genetics
MH  - Transcription Factors
MH  - Transcription, Genetic
RF  - 84
EDAT- 2003/05/28 05:00
MHDA- 2003/07/24 05:00
CRDT- 2003/05/28 05:00
PHST- 2003/05/28 05:00 [pubmed]
PHST- 2003/07/24 05:00 [medline]
PHST- 2003/05/28 05:00 [entrez]
AID - 10.1002/jemt.10339 [doi]
PST - ppublish
SO  - Microsc Res Tech. 2003 Jun 15;61(3):300-7. doi: 10.1002/jemt.10339.