PMID- 9359473
OWN - NLM
STAT- MEDLINE
DCOM- 19971230
LR  - 20190813
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 133
IP  - 1
DP  - 1997 Sep 30
TI  - Regulation of cytochrome P450 cholesterol side-chain cleavage, 3 
      beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase type 1 and 
      estradiol-17 beta-hydroxysteroid dehydrogenase mRNA levels by calcium in human 
      choriocarcinoma JEG-3 cells.
PG  - 63-71
AB  - In human placenta the cytochrome P450 side-chain cleavage (P450scc) and 3 
      beta-hydroxysteroid dehydrogenase type 1 (3 beta-HSD-1) convert cholesterol and 
      pregnenolone producing progesterone, whereas 17 beta-hydroxysteroid dehydrogenase 
      type 1 (17 beta-HSD-1) mediates the interconversion of estrone and estradiol. We 
      have examined the effects of calcium on phorbol ester- and cAMP-induced P450scc, 
      3 beta-HSD-1 and 17 beta-HSD-1 mRNAs in human JEG-3 cells. A23187 increased in a 
      dose-dependent fashion in the 1.3 kb 17 beta-HSD-1 mRNA whereas a weaker increase 
      followed by a gradual depletion effect of A23187 was observed on 3 beta-HSD-1 
      mRNA. No significant effect of A23187 on P450scc mRNA was observed. Using 0.50 
      microM of A23187 the induction of 3 beta-HSD-1 and 17 beta-HSD-1 mRNAs was 
      maximum within about 6 h whereas P450scc mRNA levels stayed unaffected throughout 
      the time-course period. The action of A23187 was synergistic on cAMP-stimulated 
      17 beta-HSD-1 mRNA levels, while in a dose-dependent manner A23187 progressively 
      depleted 3 beta-HSD-1 and P450scc mRNA abundance probably by activation of a 
      calcium-/calmodulin-dependent phosphodiesterase. On the phorbol 12-myristate, 
      13-acetate (PMA)-stimulated 3 beta-HSD-1, 17beta-HSD-1 and P450scc mRNA levels 
      only the lowest concentration of A23187 potentialized the PMA effect on the 17 
      beta-HSD-1 mRNA levels. Using thapsigargin (TG), a cell-permeable sesquiterpene 
      lactone that releases calcium by inhibiting sarco/endoplasmic reticular 
      calcium-ATPase, our data indicated the presence in JEG-3 cells of TG-sensitive 
      and TG-insensitive calcium-ATPases regulating 3 beta-HSD-1 and 17 beta-HSD-1 mRNA 
      levels. These results emphasized the complexity of calcium contribution with the 
      protein kinase A and C pathways in the regulation of P450scc, 3 beta-HSD-1 and 17 
      beta-HSD-1 mRNA levels. In addition, the different sensitivity of these genes to 
      calcium suggest they could be activated by different subclasses of PKCs.
FAU - Beaudoin, C
AU  - Beaudoin C
AD  - Molecular Endocrinology Laboratory, CHUQ, CHUL Research Center, Laval, Quebec, 
      Canada.
FAU - Bonenfant, M
AU  - Bonenfant M
FAU - Tremblay, Y
AU  - Tremblay Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (RNA, Messenger)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.1.- (17-Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.145 (Progesterone Reductase)
RN  - EC 1.1.1.51 (3 (or 17)-beta-hydroxysteroid dehydrogenase)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
RN  - EC 5.3.3.- (Steroid Isomerases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 17-Hydroxysteroid Dehydrogenases/drug effects/genetics/*metabolism
MH  - Calcium/*pharmacology
MH  - Cholesterol/*metabolism
MH  - Cholesterol Side-Chain Cleavage Enzyme/drug effects/*metabolism
MH  - Choriocarcinoma/*enzymology/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Multienzyme Complexes/drug effects/genetics/*metabolism
MH  - Progesterone Reductase/drug effects/genetics/*metabolism
MH  - RNA, Messenger/drug effects/*metabolism
MH  - Steroid Isomerases/drug effects/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Uterine Neoplasms/*enzymology/genetics
EDAT- 1997/11/14 00:00
MHDA- 1997/11/14 00:01
CRDT- 1997/11/14 00:00
PHST- 1997/11/14 00:00 [pubmed]
PHST- 1997/11/14 00:01 [medline]
PHST- 1997/11/14 00:00 [entrez]
AID - S0303-7207(97)00143-3 [pii]
AID - 10.1016/s0303-7207(97)00143-3 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 1997 Sep 30;133(1):63-71. doi: 
      10.1016/s0303-7207(97)00143-3.