ACTH sensitivity of isolated human pathological adrenocortical cells: variability of responses in aldosterone, corticosterone, deoxycorticosterone and cortisol production.
In vitro aldosterone, deoxycorticosterone, corticosterone and cortisol production of human adrenocortical cells derived from adenomas (Conn's syndrome, Cushing's syndrome), from hyperplastic adrenals (Cushing's syndrome) and from adrenals surrounding aldosteronoma are described. Cells from adenomas causing either Cushing's syndrome or Conn's syndrome harboured the highest basal and ACTH-stimulated corticosteroid production. Adrenocortical cells derived from micronodular hyperplasia causing Cushing's syndrome and cells from cortisol producing adenoma displayed predominantly cortisol and corticosterone secretion both under basal conditions and following stimulation with ACTH. Aldosteronoma cells showed highly variable aldosterone, deoxycorticosterone, corticosterone and cortisol response to ACTH. However, in aldosteronoma cell suspensions, the basal and ACTH-stimulated ratios of aldosterone to cortisol were increased when compared to ratios of steroids produced by cells from other adrenal tissues. Chronic treatment with spironolactone of patients with Conn's syndrome before surgery was associated with a decreased ratio of aldosterone to corticosterone, revealing that 18-hydroxylase in aldosteronoma cells may be inhibited during long-term therapy. Non-tumorous cells isolated from adrenals surrounding aldosteronoma displayed less aldosterone prior to and after stimulation with ACTH than aldosteronoma cells.
D000236:Adenoma / Q000378:metabolism*; D000302:Adrenal Cortex / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000096:biosynthesis; D003345:Corticosterone / Q000096:biosynthesis; D003366:Cosyntropin / Q000494:pharmacology; D003480:Cushing Syndrome / Q000378:metabolism; D003900:Desoxycorticosterone / Q000096:biosynthesis; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D006929:Hyperaldosteronism / Q000378:metabolism; D066298:In Vitro Techniques
D000305:Adrenal Cortex Hormones; D003366:Cosyntropin; D003900:Desoxycorticosterone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone