Chemically Induced Adrenocortical Degenerative Lesions

Yarrington, J. T.; Reindel, J. F.

doi:10.1007/978-3-642-60996-1_63

Cited by 8 publications

(2 citation statements)

References 34 publications

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“…In contrast, there were no significant changes in the plasma corticosterone level, and this was thought to be partly due to its wide interindividual variability. It is known that the basal level of blood corticosteroid is not a sensitive marker for impaired adrenal steroidogenesis (Hinson and Raven 2006;Yarrington and Reindel 1996). Thus, it was shown in this study that at least for HSD3B and CYP11B1 inhibitors, the precursors are more sensitive than corticosterone to evaluate the effect of compounds on adrenal steroidogenesis.…”

Section: Discussionmentioning

confidence: 71%

Usefulness of Simultaneous Measurement of Plasma Steroids, Including Precursors, for the Evaluation of Drug Effects on Adrenal Steroidogenesis in Rats

et al. 2017

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The aim of this study was to evaluate the usefulness of simultaneous measurement of plasma steroids, including precursors, for the evaluation of drug effects on adrenal steroidogenesis in vivo. Plasma concentrations of corticosterone and its precursors were examined in rats dosed with compounds that affect adrenal steroidogenesis via different modes of action as well as the relationships of the changes with blood chemistry and adrenal histopathology. Male rats were dosed with tricresyl phosphate, aminoglutethimide, trilostane (TRL), metyrapone (MET), ketoconazole (KET), or mifepristone for 7 days. In the TRL, MET, and KET groups, precursor levels were markedly increased, while there were no significant changes in the corticosterone level, suggesting that the precursors are more sensitive biomarkers to detect the effect on adrenal steroidogenesis. Also, the precursors with increased levels were those that are normally metabolized by the inhibited enzymes, reflecting the modes of action of the compounds. In addition, different patterns of changes were observed in blood chemistry and histopathology, supporting the mechanism suggested by the steroid changes. These results show that simultaneous measurement of plasma steroids, including precursors, can be a valuable method to sensitively evaluate drug effects on adrenal steroidogenesis and to investigate the underlying mechanisms.

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Section: Discussionmentioning

confidence: 71%

Usefulness of Simultaneous Measurement of Plasma Steroids, Including Precursors, for the Evaluation of Drug Effects on Adrenal Steroidogenesis in Rats

et al. 2017

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“…On the other hand, similar tendency was not observed in the KET 150 mg/kg group, suggesting impaired corticosterone secretion. However, there was no significant difference between the 0.5% MC and KET groups, further supporting low sensitivity of the basal blood corticosterone level as a marker for impaired adrenal steroidogenesis (Yarrington and Reindel, 1996).…”

Section: Discussionmentioning

confidence: 78%

Dose- and time-dependent changes in blood and adrenal levels of multiple steroids in rats after administration of ketoconazole with or without ACTH

et al. 2019

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To verify simultaneous measurement of blood levels of adrenal steroids as a tool to evaluate drug effects on adrenal steroidogenesis, dose-and time-dependent changes in blood levels of corticosterone and its precursors (pregnenolone, progesterone and deoxycorticosterone), as well as their relationship with the pathological changes in the adrenal gland, were examined in rats dosed with ketoconazole (KET). Also examined were whether effects on adrenal steroidogenesis that were not obvious in the blood steroid levels after sole administration of KET could be revealed by post-administration of ACTH, and the correlation between the blood and adrenal steroid levels. Male rats were dosed with 15, 50, or 150 mg/kg of KET for 1 or 7 days with or without ACTH, and the blood and adrenal concentrations of the steroids were measured. KET increased the blood deoxycorticosterone level even at a dose level and time point at which histopathological changes were not obvious. KET-induced changes in blood levels of other steroids were revealed by ACTH, and the blood and adrenal levels were generally correlated especially after ACTH post-administration. Thus, blood levels of adrenal steroids, including precursors, can be a sensitive and early marker of drug effects on the adrenal steroidogenesis that reflect adrenal levels of steroids. The usefulness of the multiple steroid measurement as a method for mechanism investigation of drug effects on the adrenal gland can be further enhanced by ACTH.

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