Regulation of human adrenal carcinoma cell (NCI-H295) production of C19 steroids.

• DOI: 10.1210/jcem.77.3.8396576
• Publication Date: 2014-01-08T16:57:40Z
• Authors: W E Rainey; I M Bird; C Sawetawan; N A Hanley; J L McCarthy; E A McGee; R Wester; J I Mason
• Keywords: Steroid 11-beta-hydroxylase; Steroid hormone; CYP17A1; Steroid biosynthesis; Adrenarche

The regulation of biosynthesis the adrenal C19 steroids (the so-called androgens) remains unclear. Understanding production is important when benefits these are considered on processes and diseases associated with aging. In vitro studies defining mechanisms that regulate human have been limited because difficulties in obtaining tissue. A cell line retains differentiated functions would greatly facilitate research this area. Herein, we describe use adrenocortical tumor H295 as a model to evaluate controlling C21 steroid production. cells were characterized regard ACTH, forskolin, dibutyryl cAMP (dbcAMP) responsiveness, measured by increased production, synthesis steroids, induction 17 alpha-hydroxylase cytochrome P450 (P450c17). Forskolin dbcAMP, which more effective than enhanced cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione over 48-h treatment period. Comparison relative amounts secreted under forskolin indicated primary product was cortisol (70%), followed (14%), (9%), DHEAS (7%). Cortisol also demonstrated be major examination UV-detectable after high performance liquid chromatographic separation. increases caused dbcAMP occurred concentration- time-dependent manner. key enzyme P450c17. activity approximately 2.5-, 10-, 10-fold, respectively. These effects concentration-dependent manner coincided levels P450c17 mRNA. summary, should provide much-needed study secretion glucocorticoids hormonally controlled