Primary culture system of adrenocortical cells from dogs to evaluate direct effects of chemicals on steroidogenesis

Citation
K. Morishita et al., Primary culture system of adrenocortical cells from dogs to evaluate direct effects of chemicals on steroidogenesis, TOXICOLOGY, 165(2-3), 2001, pp. 171-178
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY
ISSN journal
0300-483X → ACNP
Volume
165
Issue
2-3
Year of publication
2001
Pages
171 - 178
Database
ISI
SICI code
0300-483X(20010828)165:2-3<171:PCSOAC>2.0.ZU;2-J
Abstract
The present study was conducted to confirm the usefulness of a primary cult ure system of adrenocortical cells from dogs for detecting the direct effec ts of the chemicals on adrenal cortex. Corticosteroid levels in the culture supernatant were measured using high-performance liquid chromatography (HP LC) following 24-h incubation with the chemicals. Ketoconazole, miconazole, metyrapone, aminoglutethimide, and 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2 ,2-dichloroethane (o,p-DDD), which were known to inhibit cortisol productio n were evaluated in this system. Both viable cells and corticosteroid level s were decreased by o,p-DDD treatment. Other chemicals showed various inhib ition patterns of corticosteroid levels as follows without affecting cell v iability. Ketoconazole decreased total corticosteroids level by mainly due to the decreases in cortisol and 11-deoxycortisol levels. Miconazole decrea sed cortisol and 11-deoxycortisol levels, however, slightly increased corti costerone level. Metyrapone decreased cortisol and corticosterone levels as 11-deoxycortisol and 11-deoxycorticosterone levels were increased. Aminogl utethimide decreased total corticosteroids level by mainly decreasing corti sol, corticosterone and 11-deoxycortisol levels. These results suggested th at determination of the pattern of corticosteroid levels by HPLC in this sy stem well reflected the mode of their action on steroidogenesis. Thus, we c onclude this simple system was useful to determine the direct effects of ch emicals on steroidogenesis in the adrenal cortex. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.