title: Dehydroepiandrosterone sulfate (DHEA-S) and 3', 5'-cyclic adenosine monophosphate (cAMP) production in a cultured human adrenocortical carcinoma cell line (SW-13).
abstract: Very little has been known of the biochemical function of a human adrenocortical carcinoma cell line, SW-13. In this study, the production of several adrenal steroids and 3', 5'-cyclic adenosine monophosphate (cAMP) were investigated in this cell line. The cells were incubated in L-15 medium containing 0.1% bovine serum albumin with several reagents in an atmosphere of 5% CO2 and 95% air for 2 hours at 37 degrees C. Aldosterone (Ald), corticosterone (B), cortisol (F), dehydroepiandrosterone sulfate (DHEA-S) and cAMP were simultaneously assayed by specific radioimmunoassays in the medium and cells. Significant increases in cAMP production were observed by cholera toxin (10 ng/ml) and forskolin (10 nM), both direct stimulators of adenylate cyclase, in the cAMP concentration without an increase in the steroids. The DHEA-S concentration in the medium was significantly increased by angiotensin-II (10(-7)M), noradrenalin (3 X 10(-5) M), adrenalin (3 X 10(-5) M) or alpha-melanocyte-stimulating hormone (alpha-MSH, 10(-7) M), none of which was associated with cAMP production. Neither adrenocorticotropin (10(-10) M) nor human chorionic gonadotropin (500 mIU/ml) stimulated the release of the steroids or cAMP production. A calcium ionophore, A23187 (10(-7) M), and 12-O-tetradecanoylphorbol-13-acetate (10(-8) M), a direct stimulator of protein kinase C, stimulated the release of DHEA-S, but not those of Ald, B and F. The results suggest that SW-13 retains functioning adenylate cyclase which, however, is not linked with steroidogenesis and that DHEA-S is produced probably by the mechanisms which involve protein kinase C system or calcium ion. This report provides the first demonstration of cAMP and DHEA-S production in SW-13 and suggests that this cell line is potentially useful for investigating the mechanisms of steroidogenesis in the human adrenal cortex.
authors.affiliation: Third Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Itoh
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Horiuchi
authors.forename: M
authors.initials: M
authors.lastname: Kumagae
authors.forename: T
authors.initials: T
authors.lastname: Watabe
authors.forename: A
authors.initials: A
authors.lastname: Kanbegawa
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000378:metabolism; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D006063:Chorionic Gonadotropin; D000804:Angiotensin II; D005576:Colforsin; D000001:Calcimycin; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine