Forskolin treatment directs steroid production towards the androgen pathway in the NCI-H295R adrenocortical tumour cell line.
The human adrenocortical tumour cell line, NCI-H295, secretes steroids on the mineralocorticoid, glucocorticoid and adrenal androgen pathways. We have investigated the effects of 96 h treatment of cells in monolayer culture with either forskolin (10 microM) (a direct activator of adenylate cyclase), angiotensin II (10 nM) or no agonist ('control') on the steroidogenic phenotype of this cell line. Androstenedione, cortisol and corticosterone secreted into the medium in response to a subsequent 4 hour treatment with angiotensin II (10nM) indicated that the steroidogenic phenotype of NCI-H295 cells changes away from 17-deoxysteroid biosynthesis towards adrenal androgen production in response to forskolin. The NCI-H295R cell line therefore serves as a useful model for investigation of the differential regulation of the steroidogenic pathways in the human adrenal cortex.
Cobb
V J
VJ
Department of Clinical Biochemistry, University of Edinburgh, UK.
Williams
B C
BC
Mason
J I
JI
Walker
S W
SW
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D015383:Zona Fasciculata / Q000187:drug effects / Q000378:metabolism; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism; D015385:Zona Reticularis / Q000187:drug effects / Q000378:metabolism
D000728:Androgens; D000804:Angiotensin II; D005576:Colforsin; D000735:Androstenedione; D003345:Corticosterone; D006854:Hydrocortisone