THE EFFECTS OF OPIOID DRUGS AND OF LITHIUM ON STEROIDOGENESIS IN RAT ADRENAL CELL SUSPENSIONS

Abstract
1 The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated. 2 In medium containing normal Na+ (156 mm), opioid antagonists but not opioid agonists reduced the steroidogenic response to adrenocorticotrophic hormone1–24. (ACTH1–24) but not to dibutyryl adenosine 3′,5′ cyclic monophosphate (db cyclic AMP). 3 Replacement of 50% Na+ in the medium by choline had no effect on steroidogenesis, but further reductions in Na+ content reduced the steroidogenic activity of both ACTH1–24 and db cyclic AMP. 4 In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1–24 induced steroidogenesis. 5 Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1–24 but not to db cyclic AMP. 6 The selective inhibition of ACTH1–24-induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors. 7 The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed.