A mechanism-based fluorogenic probe for the cytochrome P-450 cholesterol side chain cleavage enzyme

1991 ◽  
Vol 56 (18) ◽  
pp. 5391-5396 ◽  
Author(s):  
Daniel J. Simpson ◽  
Clifford J. Unkefer ◽  
Thomas W. Whaley ◽  
Babetta L. Marrone
Keyword(s):  
Side Chain ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Fluorogenic Probe ◽  
Cleavage Enzyme ◽  
Cytochrome P 450

scholarly journals Stimulation of cholesterol side-chain cleavage by a luteinizing-hormone-releasing hormone (luliberin) agonist (ICI 118630) in rat Leydig cells

1983 ◽  
Vol 216 (3) ◽  
pp. 747-752 ◽  
Author(s):  
M H F Sullivan ◽  
B A Cooke
Keyword(s):  
Luteinizing Hormone ◽  
Leydig Cells ◽  
Side Chain ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Cytochrome P 450 ◽  
Stimulation Of

The action of a luliberin (luteinizing-hormone-releasing hormone) agonist (ICI 118630) and lutropin (luteinizing hormone) on the activity of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat Leydig cells has been investigated. This has been carried out by studying the metabolism of exogenous (22R)-22- and 25-hydroxycholesterol to testosterone. It was found that both hydroxycholesterols increased testosterone production to higher levels than achieved by lutropin alone. Addition of luliberin agonist but not lutropin was found to increase further the metabolism of the hydroxycholesterol to testosterone; this occurred in the presence of saturating and subsaturating levels of the hydroxycholesterols. This effect of luliberin agonist was potentiated in the presence of lutropin. The protein synthesis inhibitor, cycloheximide, inhibited the luliberin agonist-induced stimulation of the hydroxycholesterol metabolism. At low calcium levels (1.1 microM), testosterone production was increased by addition of (22R)-22-hydroxycholesterol but the luliberin agonist effect was negated. The calmodulin inhibitor trifluoperazine inhibited (22R)-22-hydroxycholesterol-stimulated steroidogenesis and negated the luliberin agonist effect. These results indicate that luliberin agonist specifically increases the synthesis of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat testis Leydig cells.

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