PMID- 11792726
OWN - NLM
STAT- MEDLINE
DCOM- 20020430
LR  - 20210217
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 43
IP  - 1
DP  - 2002 Jan
TI  - Tissue-specific transcriptional regulation of the cholesterol biosynthetic 
      pathway leads to accumulation of testis meiosis-activating sterol (T-MAS).
PG  - 82-9
AB  - Lanosterol 14alpha-demethylase (CYP51) produces follicular fluid 
      meiosis-activating sterol (FF-MAS), which is converted further to testis 
      meiosis-activating sterol (T-MAS). MAS are intermediates in the cholesterol 
      biosynthetic pathway, with the ability to trigger resumption of oocyte meiosis in 
      vitro. In contrast to the liver, where pre- and post-MAS genes are upregulated 
      coordinately at the level of transcription by a cholesterol feedback mechanism 
      through sterol regulatory element-binding proteins (SREBP), regulation differs in 
      the testis. Genes encoding pre-MAS enzymes [HMG-CoA synthase (SYN), HMG-CoA 
      reductase (RED), farnesyl diphosphate synthase (FPP), squalene synthase (SS), and 
      CYP51] are upregulated during sexual development of the testis, although not all 
      genes are turned on at the same time. Furthermore, two post-MAS genes, C-4 sterol 
      methyl oxidase and sterol Delta(7)-reductase, are expressed at low levels and are 
      not upregulated either in rat or human. This transcriptional discrepancy seems to 
      be SREBP independent. Besides cAMP/cAMP-responsive element modulator, other 
      unknown transcription factors control expression of individual cholesterogenic 
      genes during spermatogenesis. HPLC analysis shows an 8-fold increase in T-MAS 
      during development of rat testis whereas MAS is barely detectable in livers of 
      the same animals. We propose that the lack of a coordinate transcriptional 
      control over the cholesterol biosynthetic pathway contributes importantly to 
      overproduction of the signaling sterol T-MAS in testis.
FAU - Tacer, K Fon
AU  - Tacer KF
AD  - Institute of Biochemistry, Medical Center for Molecular Biology, Faculty of 
      Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
FAU - Haugen, T B
AU  - Haugen TB
FAU - Baltsen, M
AU  - Baltsen M
FAU - Debeljak, N
AU  - Debeljak N
FAU - Rozman, Damjana
AU  - Rozman D
LA  - eng
GR  - 1R03 TW 01174-01/TW/FIC 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.
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (CYP51A1 protein, human)
RN  - 0 (Cholestadienols)
RN  - 0 (Cyp51 protein, rat)
RN  - 0 (RNA, Messenger)
RN  - 19456-83-8 (4,4-dimethylcholesta-8,14-dien-3-ol)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
RN  - EC 1.14.14.154 (Cyp51 protein, mouse)
RN  - EC 1.14.14.154 (Sterol 14-Demethylase)
SB  - IM
MH  - Animals
MH  - Cholestadienols/*metabolism
MH  - Cholesterol/analysis/*biosynthesis/genetics
MH  - Cytochrome P-450 Enzyme System/genetics
MH  - *Gene Expression Regulation, Developmental
MH  - Humans
MH  - Hydroxymethylglutaryl CoA Reductases/genetics
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Organ Specificity/genetics/physiology
MH  - Oxidoreductases/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Spermatogenesis/genetics
MH  - Sterol 14-Demethylase
MH  - Testis/growth & development/*metabolism
MH  - *Transcription, Genetic
EDAT- 2002/01/17 10:00
MHDA- 2002/05/01 10:01
CRDT- 2002/01/17 10:00
PHST- 2002/01/17 10:00 [pubmed]
PHST- 2002/05/01 10:01 [medline]
PHST- 2002/01/17 10:00 [entrez]
AID - S0022-2275(20)30190-5 [pii]
PST - ppublish
SO  - J Lipid Res. 2002 Jan;43(1):82-9.