Development of an adrenocorticotropin-responsive human adrenocortical carcinoma cell line.
Abstract
The molecular mechanisms regulating adrenal steroidogenesis continue to be defined. The only current human adrenocortical cell line is the NCI-H295 and its substrains. One of the strains, H295R, has retained the ability to respond to angiotensin II (Ang II); however, it lacks ACTH responsiveness. An ACTH-responsive human adrenocortical model would add significantly to studies directed at defining the molecular control of corticosteroid biosynthesis. The objective of the study was to develop a human adrenal cell line that retained both Ang II- and ACTH-regulated corticosteroid production. Human adrenocortical carcinoma (HAC) cells were isolated from an adrenal tumor removed from a girl presenting with virilization and hypertension. Clonal populations of cells were established and characterized. HAC cells were treated with ACTH, Ang II, and forskolin, followed by examination of steroidogenic enzyme mRNA expression using quantitative real-time PCR and steroid production. HAC clone 15 (HAC15) cells responded to treatment with ACTH, Ang II, and forskolin, with increased cortisol and aldosterone production. ACTH, Ang II, and forskolin also increased expression of mRNA, encoding all enzymes needed for cortisol and aldosterone biosynth...Continue Reading
References
Citations
Inhibins and activins: their roles in the adrenal gland and the development of adrenocortical tumors
Role of Cryptochrome-1 and Cryptochrome-2 in Aldosterone-Producing Adenomas and Adrenocortical Cells
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