Document Detail

Effect of myxothiazol on Leydig cell steroidogenesis: inhibition of luteinizing hormone-mediated testosterone synthesis but stimulation of basal steroidogenesis.
MedLine Citation:
PMID:  17332065     Owner:  NLM     Status:  MEDLINE    
Studies of MA-10 Leydig cells have shown that intact mitochondria with active respiration are essential for LH-induced Leydig cell steroidogenesis. To further elucidate the role played by mitochondria in steroidogenesis, we examined the effects of the perturbation of the mitochondrial electron transport chain with myxothiazol (MYX) on testosterone production by primary cultures of Brown Norway rat Leydig cells. Analysis of the steroidogenic pathway revealed that cAMP production and the activities of each of 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/C17-20 lyase, and 17beta-hydroxysteroid dehydrogenase were inhibited by MYX and that LH-stimulated testosterone production was suppressed. In contrast to the inhibition of LH-stimulated testosterone production by MYX, the incubation of Leydig cells with MYX in the absence of LH stimulated testosterone production. Although testosterone production was increased, steroidogenic acute regulatory protein was decreased in response to MYX, not increased as could be expected. Additional electron transport chain inhibitors had stimulatory effects on testosterone production that were similar to those of MYX, strongly suggesting that the effect of MYX on basal testosterone production is related to its effect on the mitochondrial electron transport chain. Finally, incubation of the cells with a combination of MYX and the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetracetic acid tetrakis acetoxymethyl ester suppressed MYX-mediated increased basal steroidogenesis but had no effect on hydroxycholesterol-mediated steroidogenesis. Taken together, these results indicate that inhibition of the mitochondrial electron transport chain can block LH-stimulated testosterone production through suppression of a number of steps of the steroidogenic pathway but also stimulates basal testosterone production through a calcium-mediated mechanism.
Andrew S Midzak; June Liu; Barry R Zirkin; Haolin Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-03-01
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-17     Completed Date:  2007-07-24     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2583-90     Citation Subset:  AIM; IM    
Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
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MeSH Terms
Leydig Cells / drug effects*,  metabolism*
Luteinizing Hormone / pharmacology*
Methacrylates / pharmacology
Mitochondria / drug effects,  physiology
Rats, Inbred Strains
Signal Transduction
Steroids / biosynthesis*
Testosterone / biosynthesis*
Thiazoles / pharmacology
Grant Support
Reg. No./Substance:
0/Methacrylates; 0/Steroids; 0/Thiazoles; 58-22-0/Testosterone; 76706-55-3/myxothiazol; 9002-67-9/Luteinizing Hormone
Comment In:
Endocrinology. 2007 Jun;148(6):2581-2   [PMID:  17507576 ]

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