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.

Inhibition of the luteinizing hormone-dependent induction of cholesterol side chain cleavage enzyme in immature rat Leydig cells by Sertoli cell products

1995 ◽  
Vol 132 (5) ◽  
pp. 627-634 ◽  
Author(s):  
Lizzy van Haren ◽  
J Franny Flinterman ◽  
Focko FG Rommerts
Keyword(s):  
Luteinizing Hormone ◽  
Sertoli Cell ◽  
Leydig Cells ◽  
Side Chain ◽  
Inhibitory Effects ◽  
Isolated Rat Hepatocytes ◽  
Immature Rat ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

Van Haren L, Flinterman JF, Rommerts FFG. Inhibition of the luteinizing hormone-dependent induction of cholesterol side chain cleavage enzyme in immature rat Leydig cells by Sertoli cell products. Eur J Endocrinol 1995;132:627–34. ISSN 0801–4643 The modulation of the luteinizing hormone (LH) induction of cholesterol side chain cleavage (CSCC) enzyme in immature rat Leydig cells was studied using rat Sertoli cell-conditioned medium (SCCM), which stimulates short-term endogenous steroid production. Luteinizing hormone increased the CSCC enzyme activity 10-fold in cells cultured for 7 days in the absence of hormones. This enzyme induction was abolished almost completely in the presence of SCCM. The inhibition was dose dependent (halfmaximal effect at 5 mg protein/l) and paralleled by a decrease in the amount of cytochrome P-450sec P-450scc) enzyme. There were no indications for loss of cell viability. The inhibitory action of SCCM could be localized at the level of adenylate cyclase activation and at steps beyond cyclic adenosine monophosphate production. The inhibition was not specific for Sertoli cell products because conditioned media from different cell lines and media from isolated rat hepatocytes displayed similar effects. Trypsin treatment of SCCM destroyed the activity whereas the bioactivity could resist heating for 5 min at 100°C. Generally occurring (growth) factors, such as epidermal growth factor or tumor necrosis factor α, may have contributed to the observed inhibitory effects of SCCM. These inhibitory effects of Sertoli cell products in vitro are in contrast to stimulatory effects of Sertoli cells on Leydig cell steroidogenesis in vivo after FSH administration. Focko FG Rommerts, Department of Endocrinology & Reproduction, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands

scholarly journals Evaluation of relative roles of LH and FSH in regulation of differentiation of Leydig cells using an ethane 1,2-dimethylsulfonate-treated adult rat model

2003 ◽  
Vol 176 (1) ◽  
pp. 151-161 ◽  
Author(s):  
V Sriraman ◽  
MR Sairam ◽  
AJ Rao
Keyword(s):  
Leydig Cells ◽  
Serum Testosterone ◽  
Side Chain ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Lh Receptor ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme

The relative role of LH and FSH in regulation of differentiation of Leydig cells was assessed using an ethane 1,2-dimethylsulfonate (EDS)-treated rat model in which endogenous LH or FSH was neutralized from day 3 to day 22 following EDS treatment. Serum testosterone and the in vitro response of the purified Leydig cells to human chorionic gonadotropin (hCG) was monitored. In addition RNA was isolated from the Leydig cells to monitor the steady-state mRNA levels by RT-PCR for 17alpha-hydroxylase, side chain cleavage enzyme, steroidogenic acute regulatory protein (StAR), LH receptor, estrogen receptor (ER-alpha) and cyclophilin (internal control). Serum testosterone was undetected and the isolated Leydig cells secreted negligible amount of testosterone on stimulation with hCG in the group of rats that were treated with LH antiserum following EDS treatment. RT-PCR analysis revealed the absence of message for cholesterol side chain cleavage enzyme and 17alpha-hydroxylase although ER-alpha and LH receptor mRNA could be detected, indicating the presence of undifferentiated precursor Leydig cells. In contrast, the effects following deprival of endogenous FSH were not as drastic as seen following LH neutralization. Deprival of endogenous FSH in EDS-treated rats led to a significant decrease in serum testosterone and in vitro response to hCG by the Leydig cells. Also, there was a significant decrease in the steady-state mRNA levels of 17alpha-hydroxylase, cholesterol side chain cleavage enzyme, LH receptor and StAR as assessed by a semiquantitative RT-PCR. These results establish that while LH is obligatory for the functional differentiation of Leydig cells, repopulation of precursor Leydig cells is independent of LH, and also unequivocally establish an important role for FSH in regulation of Leydig cell function.

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