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

The role of the cytoskeleton in corticosteroid secretion in normal human adrenal gland was investigated in vitro, using the perifusion technique and confocal laser scanning microscopy. Vinblastine, which selectively disrupted microtubules in adrenocortical cells, did not modify the basal release of cortisol but induced a 58% inhibition of the response to adrenocorticotropic hormone (ACTH). In contrast, vinblastine did not alter dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-induced steroid secretion. Cytochalasin B treatment caused disappearance of microfilaments and blocked the stimulatory action of ACTH and DBcAMP 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 first evidence for an action of cytoskeleton inhibitors on cortisol release from normal human adrenocortical cells, show that microtubules are involved in the mechanism of action of ACTH at a step preceding adenosine 3',5'-cyclic monophosphate formation, whereas microfilaments are involved in a late and common step of adrenal steroidogenesis.