Screening for drug-induced alterations in the production and release of steroid hormones by porcine adrenocortical cells in vitro

Toxicology in Vitro : an International Journal Published in Association with BIBRA
L P JagerH C Widjaja-Greefkes

Abstract

To screen drugs rapidly and at minimal expense for their potential to alter steroidogenesis, an in vitro model using porcine adrenocortical cells was developed. Pregnenolone, progesterone, deoxycorticosterone or corticosterone (all at 1 muM) were used as substrates. Drug-induced changes in the production/release of aldosterone were measured after 1-hr incubation. With pregnenolone, drug-induced effects on the release of nine steroids (aldosterone, corticosterone, cortisol, deoxycortisol, testosterone, progesterone, HO-progesterone, androstenedione, dehydroepiandrosterone) were monitored simultaneously. For assessment of cell viability and the amount of steroids produced/released, a cheap, simple modified Krebs solution was at least comparable to an elaborate cell culture medium. Within the conditions adopted, the cell suspension reacted to varying potassium concentrations as expected. ACTH stimulated steroid production/release only without added substrate. 11 agents known to interfere with steroid biogenesis were tested at 0.1-100 muM. Although all known points of action of the test compounds were located, several showed additional activity. Spironolactone shifted steroid biogenesis from aldosterone and cortisol towards androge...Continue Reading

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