Corticosterone has direct inhibitory effect on the expression of peptide hormone receptors, 11 beta-HSD and glucose oxidation in cultured adult rat Leydig cells.
The present study was designed to investigate the dose-dependent direct effect of corticosterone on the expression of peptide hormone receptors, 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) and glucose oxidation in cultured adult rat Leydig cells. Leydig cells were isolated from the testis of normal adult male albino rats, purified on discontinuous Percoll gradient and plated in culture plates/flasks overnight at 34 degrees C in a CO(2) incubator under 95% air and 5% CO(2) using DME/F12 medium containing 1% fetal bovine serum. After the attachment of cells, serum containing medium was removed and cells were exposed to different doses (0, 50, 100, 200, 400 and 800 nM) of corticosterone using serum-free fresh medium for 24h at 34 degrees C. At the end of exposure period, cells were utilized for the quantification of cell-surface LH, prolactin, insulin receptors and their mRNA expression, the activity and mRNA expression of 11 beta-HSD and glucose oxidation. Testosterone production was estimated in cell pellets and in culture media. At all doses employed, corticosterone significantly decreased the production of testosterone by Leydig cells. The concentration of cell-surface LH and prolactin receptors were significantly reduced after corticosterone exposure whereas the concentration of insulin receptor was diminished only at 200-800 nM doses of corticosterone. The levels of LH and prolactin receptor mRNAs were significantly decreased after corticosterone (100-800 nM) exposure whereas the mRNA level of insulin receptor was significantly reduced only at 800 nM dose of corticosterone. 11 beta-HSD mRNA expression as well as the activity was significantly inhibited by corticosterone treatment. Glucose oxidation was markedly inhibited by corticosterone exposure in a dose-dependent manner. It is concluded from this in vitro study that corticosterone induces steroidogenic lesion in testicular Leydig cells by decreasing the number of cell-surface LH, prolactin and insulin receptors, the activity of 11 beta-HSD and their mRNA levels and glucose oxidation.
Rengarajan
Srinivasan
S
Department of Endocrinology, Dr. ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
Balasubramanian
Karundevi
K
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D051381:Rats; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018000:Receptors, Peptide; D042842:11-beta-Hydroxysteroid Dehydrogenases; D005947:Glucose; D003345:Corticosterone