Regulation of steroidogenesis in rat leydig cells in culture: Effect of human chorionic gonadotropin and dibutyryl cyclic AMP on the synthesis of cholesterol side chain cleavage cytochrome P-450 and adrenodoxin

1985 ◽  
Vol 238 (2) ◽  
pp. 378-387 ◽  
Author(s):  
Christen M. Anderson ◽  
Carole R. Mendelson
Keyword(s):  
Cyclic Amp ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Leydig Cells ◽  
Side Chain ◽  
Dibutyryl Cyclic Amp ◽  
Side Chain Cleavage ◽  
Cells In Culture ◽  
Chain Cleavage ◽  
Cytochrome P 450

scholarly journals Calmidazolium is a potent stimulator of steroidogenesis via mechanisms not involving cyclic AMP, calcium or protein synthesis

1992 ◽  
Vol 281 (1) ◽  
pp. 291-296 ◽  
Author(s):  
M S K Choi ◽  
B A Cooke
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Leydig Cells ◽  
Dose Range ◽  
Protein Translation ◽  
Side Chain ◽  
Dibutyryl Cyclic Amp ◽  
Adrenocortical Cells ◽  
Potent Stimulator ◽  
Chain Cleavage

This study reports an unexpected effect of calmidazolium on steroidogenesis. In contrast with previous work, which established that calmidazolium inhibits hormone-stimulated testosterone production in rat Leydig cells, the present study demonstrates that this compound is a potent stimulator of steroidogenesis when added by itself; this stimulation (approx. 10-fold in a 2 h incubation), was obtained over a narrow dose range (e.g.1-10 microM) in mouse and rat Leydig cells and in rat adrenocortical cells. The same concentrations of calmidazolium decreased basal cyclic AMP to undetectable levels in rat Leydig cells. Also, cyclic AMP stimulated with luteinizing hormone (LH), cholera toxin and forskolin was inhibited by calmidazolium (ED50 2 microM). In contrast with the actions of LH and cyclic AMP analogues on steroidogenesis, the effect of calmidazolium was not inhibited by removal of extracellular Ca2+, or by the addition of La3+ (a Ca(2+)-entry blocker), or the addition of cycloheximide (an inhibitor of protein translation). However, like dibutyryl cyclic AMP, calmidazolium-stimulated steroidogenesis was inhibited by aminoglutethimide, an inhibitor of cholesterol side-chain cleavage. Another calmodulin inhibitor, trifluoperazine, did not stimulate steroidogenesis. It is concluded that calmidazolium has a similar effect on steroidogenesis to LH, but by-passes the requirements for cyclic AMP, Ca2+, and protein synthesis. Calmidazolium is therefore a potentially important probe for elucidating the mechansims of control of steroidogenesis.

Biosynthesis of Cholesterol Side-Chain Cleavage Cytochrome P-450 in Human Fetal Adrenal Cells in Culture*

Endocrinology ◽  
1983 ◽  
Vol 112 (6) ◽  
pp. 2039-2045 ◽  
Author(s):  
MASAO OHASHI ◽  
EVAN R. SIMPSON ◽  
J. IAN MASON ◽  
MICHAEL R. WATERMAN
Keyword(s):  
Side Chain ◽  
Adrenal Cells ◽  
Side Chain Cleavage ◽  
Cells In Culture ◽  
Chain Cleavage ◽  
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.

scholarly journals A role for calmodulin in the regulation of steroidogenesis

1981 ◽  
Vol 90 (2) ◽  
pp. 402-407 ◽  
Author(s):  
PF Hall ◽  
S Osawa ◽  
CL Thomasson
Keyword(s):  
Cyclic Amp ◽  
Adrenal Tumor ◽  
Side Chain ◽  
Dibutyryl Cyclic Amp ◽  
Steroid Production ◽  
Steroid Synthesis ◽  
Side Chain Cleavage ◽  
Cleavage Activity ◽  
Chain Cleavage

Two approaches were used to study the possible role of calmodulin in the regulation of steroid synthesis by mouse adrenal tumor cells: trifluoperazine was used as an inhibitor of calmodulin and liposomes were used to deliver calmodulin into the cells. Trifluoperazine inhibits three steroidogenic responses to both ACTH and dibutyryl cyclic AMP: (a) increase in steroid production, (b) increased transport of cholesterol to mitochondria, and (c) increased side-chain cleavage by mitochondria isolated from cells incubated with ACTH or dibutyryl cyclic AMP. When calmodulin is introduced into the cells via liposomes, steroid synthesis is slightly stimulated. When calmodulin extensively dialyzed against EGTA, this stimulation is abolished. Ca(2+) introduced via liposomes was also without effect. However, when both calmodulin and Ca(2+) are introduced via liposomes (either in separate liposomes or in the same liposomes), steroid synthesis is stimulated. This stimulation does not occur when either anticalmodulin antibodies or EGTA is also present in the liposomes or when trifluoperazine is present in the incubation medium. Calmodulin and Ca(2+) presented together in liposomes to the cells stimulate transport of cholesterol to mitochondria, and side-chain cleavage activity is greater in mitochondria isolated from cells previously fused with liposomes containing calmodulin and Ca(2+) than in mitochondria from cells fused with liposomes containing buffer only. These observations suggest that calmodulin may be involved in regulating the transport of cholesterol to mitochondria, a process which is stimulated by ACTH and dibutyryl cyclic AMP and which may account, at least in part, for the increase in steroid synthesis produced by these agents.

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