This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Parmar, J. Articles by Rainey, W. E. Search for Related Content PubMed PubMed Citation Articles by Parmar, J. Articles by Rainey, W. E. Related Collections Adrenal and Hypertension Endocrine Oncology

Development of an Adrenocorticotropin-Responsive Human Adrenocortical Carcinoma Cell Line

Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912

Address all correspondence and requests for reprints to: Dr. William E. Rainey, Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912. E-mail: wrainey{at}mcg.edu.

Context: 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.

Objective: The objective of the study was to develop a human adrenal cell line that retained both Ang II- and ACTH-regulated corticosteroid production.

Design: 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.

Results: 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 biosynthesis, namely steroidogenic acute regulatory protein, cholesterol side-chain cleavage, cytochrome P450 17-hydroxylase-17, 20-lyase, 3β-hydroxysteroid dehydrogenase type II, 21-hydroxylase, 11β-hydroxylase, and 11β-aldosterone synthase. In addition, the cells expressed mRNA for ACTH receptor (MC2R) and Ang II receptor. MC2R protein was also expressed in HAC15 cells.

Conclusion: The current study describes the development and characterization of an ACTH- and Ang II-responsive human adrenal cell line. The HAC15 cell line should provide an important model system for defining the molecular mechanisms regulating aldosterone and cortisol production.

This article has been cited by other articles:

				X. Hu, J. D. Dietz, C. Xia, D. R. Knight, W. T. Loging, A. H. Smith, H. Yuan, D. A. Perry, and J. Keiser Torcetrapib Induces Aldosterone and Cortisol Production by an Intracellular Calcium-Mediated Mechanism Independently of Cholesteryl Ester Transfer Protein Inhibition Endocrinology, May 1, 2009; 150(5): 2211 - 2219. [Abstract] [Full Text] [PDF]

				A. Hoeflich and M. Bielohuby Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2 J. Mol. Endocrinol., March 1, 2009; 42(3): 191 - 203. [Abstract] [Full Text] [PDF]