Document Detail


Stimulation of cholesterol side-chain cleavage enzyme activity by cAMP and hCG in MA-10 Leydig tumor cells.
MedLine Citation:
PMID:  2855024     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Using a cloned Leydig tumor cell line (designated MA-10), we have studied the activity of cholesterol side-chain (CSCC) enzyme, the rate-determining step in steroidogenesis, in mitochondria isolated from cells pretreated either with human chorionic gonadotropin (hCG) or dibutyryl cyclic adenosine monophosphate (dbcAMP). Results showed a slight but significant increase in CSCC activity with treatment by cAMP (25% increase) and hCG (60% increase), as compared to mitochondria isolated from nontreated control cells. However, this stimulation of CSCC activity appears to be of limited significance when compared to the approximately 1000-fold or greater increase observed in progesterone production in the presence of hCG or dbcAMP. On the other hand, unstimulated MA-10 cells or isolated mitochondria efficiently converted 25-hydroxycholesterol and 22R-hydroxycholesterol into progesterone, and this conversion was not affected by cycloheximide. The addition of cholesterol to intact cells or to isolated mitochondria did not affect progesterone production. Our observations clearly indicate that given the proper hydroxy substrates (22R-hydroxycholesterol or 25-hydroxycholesterol), MA-10 Leydig cells are able to convert them into progesterone without any stimulation by steroidogenic stimuli, i.e. cAMP or hCG. Since MA-10 Leydig cells can efficiently convert 22R-hydroxycholesterol--an intermediate in CSCC reaction--into progesterone, these results suggest that the key regulatory step in the mechanism of trophic hormone-stimulated steroid production is the first hydroxylation step of the 3 sequential monooxygenation reactions involved in the conversion of cholesterol to pregnenolone.
Authors:
L R Chaudhary; D M Stocco
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochimie     Volume:  70     ISSN:  0300-9084     ISO Abbreviation:  Biochimie     Publication Date:  1988 Dec 
Date Detail:
Created Date:  1989-07-14     Completed Date:  1989-07-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1264604     Medline TA:  Biochimie     Country:  FRANCE    
Other Details:
Languages:  eng     Pagination:  1799-806     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430.
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MeSH Terms
Descriptor/Qualifier:
Allosteric Regulation
Animals
Cholesterol Side-Chain Cleavage Enzyme / metabolism*
Chorionic Gonadotropin / pharmacology*
Cyclic AMP / pharmacology*
Cycloheximide / pharmacology
Enzyme Induction
Hydroxycholesterols / metabolism
Leydig Cell Tumor / enzymology,  metabolism
Mitochondria / enzymology
Progesterone / biosynthesis
Substrate Specificity
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
HD 00685/HD/NICHD NIH HHS; HD 17481/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Hydroxycholesterols; 57-83-0/Progesterone; 60-92-4/Cyclic AMP; 66-81-9/Cycloheximide; EC 1.14.15.6/Cholesterol Side-Chain Cleavage Enzyme

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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