Abstract
Clinical and experimental studies have shown the adverse effects of glucocorticoid deficiency/metyrapone treatment on testicular Leydig cell testosterone production. However, molecular mechanisms that underlie the effects of glucocorticoid deficiency on Leydig cell steroidogenesis are not yet determined. Therefore, the present study was designed to assess the mechanism of this phenomenon. Following metyrapone-induced corticosterone deficiency, serum testosterone, and Leydig cell 14C-glucose oxidation were decreased. StAR mRNA and protein levels were significantly increased in Leydig cells of corticosterone-deficient animals. mRNA levels and the specific activities of P(450)scc and 17beta-HSD were decreased by corticosterone deficiency, whereas the activity and mRNA of 3beta-HSD were increased. Simultaneous administration of corticosterone prevented its deficiency-induced changes in Leydig cells. Our results show that metyrapone-induced corticosterone deficiency impairs Leydig cell testosterone production by decreasing the activities of steroidogenic enzymes and their mRNA expression and glucose oxidation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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17-Hydroxysteroid Dehydrogenases / genetics
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17-Hydroxysteroid Dehydrogenases / metabolism
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3-Hydroxysteroid Dehydrogenases / genetics
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3-Hydroxysteroid Dehydrogenases / metabolism
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Animals
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Blotting, Western
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Carbon Radioisotopes
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Cholesterol Side-Chain Cleavage Enzyme / genetics
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Cholesterol Side-Chain Cleavage Enzyme / metabolism
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Corticosterone / blood
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Corticosterone / deficiency*
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Corticosterone / therapeutic use
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Gene Expression Regulation / drug effects
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Glucose / metabolism
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Hormone Replacement Therapy*
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Leydig Cells / drug effects
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Leydig Cells / enzymology
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Leydig Cells / metabolism*
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Male
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Metyrapone / pharmacology
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Oxidation-Reduction / drug effects
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Reverse Transcriptase Polymerase Chain Reaction
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Testosterone / biosynthesis*
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Testosterone / blood
Substances
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Carbon Radioisotopes
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Phosphoproteins
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RNA, Messenger
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steroidogenic acute regulatory protein
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Testosterone
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17-Hydroxysteroid Dehydrogenases
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3-Hydroxysteroid Dehydrogenases
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Cholesterol Side-Chain Cleavage Enzyme
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Glucose
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Corticosterone
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Metyrapone