Effects of angiotensin II and ACTH on normal and tumourous human adrenocortical cells.
Isolated adrenocortical cells from 6 patients with a 'normal' zona fasciculata, 4 patients with a 'normal' zona glomerulosa, and tumour cells from 1 adrenocortical adenoma and 1 carcinoma were incubated with and without increasing concentrations of ACTH 1-24 (10(-13) M to 10(-9) M) or Asp1-Ile5-angiotensin II (10(-11) M to 10(-7) M). In 4/5 'normal' cases, cortisol was clearly stimulated by 10(-13) M ACTH. The maximum of the dose-response curve (5-fold stimulation) was reached at 10(-10) M ACTH. Angiotensin II (AII) started to stimulate 'normal' cells at 10(-11) M with a maximum (2-fold stimulation) at 10(-9) M. Aldosterone production by 'normal' cells was less markedly stimulated by ACTH and AII, although the threshold doses for both peptides were similar to those of the cortisol response curves. The cells of the adrenocortical adenoma from a patient with Cushing's syndrome produced large amounts of cortisol and small amounts of aldosterone, both steroids being clearly stimulated by ACTH and AII. The adrenocortical carcinoma cells produced small amounts of cortisol and no aldosterone. Cortisol production responded to ACTH, but not to AII. The results suggest that an activated renin-angiotensin system may stimulate the zona fasciculata, since 10(-11) M AII (= 10 pg AII/ml) is a normal plasma AII concentration on an unrestricted diet. Clinical evidence supporting this thesis is reviewed. However, cortisol production itself will rarely be increased by AII in vivo, since a down-regulation of ACTH would occur.
D000236:Adenoma / Q000378:metabolism; D000302:Adrenal Cortex / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects
D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone