EFFECTS OF SELECTIVE DISRUPTION OF CYTOSKELETAL ELEMENTS ON STEROID-SECRETION BY HUMAN ADRENOCORTICAL SLICES

The role of the cytoskeleton in corticosteroid secretion in normal hum an adrenal gland was investigated in vitro, using the perifusion techn ique and confocal laser scanning microscopy. Vinblastine, which select ively disrupted microtubules in adrenocortical cells, did not modify t he basal release of cortisol but induced a 58% inhibition of the respo nse to adrenocorticotropic hormone (ACTH). In contrast, vinblastine di d not alter dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-in duced steroid secretion. Cytochalasin B treatment caused disappearance of microfilaments and blocked the stimulatory action of ACTH and DBcA MP on cortisol secretion. beta,beta'-Iminodipropionitrile disorganized the cytokeratin intermediate filaments but did not alter spontaneous and ACTH-evoked cortisol release. These results, which provide the fir st evidence for an action of cytoskeleton inhibitors on cortisol relea se from normal human adrenocortical cells, show that microtubules are involved in the mechanism of action of ACTH at a step preceding adenos ine 3',5'-cyclic monophosphate formation, whereas microfilaments are i nvolved in a late and common step of adrenal steroidogenesis.