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In Search of Adrenocortical Stem and Progenitor Cells

Department of Internal Medicine (A.C.K., F.M.B., J.H.H., T.E., V.R.K., K.T.K., J.O.S., D.P.S., A.T., G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan 48109; and Biomedical Sciences (W.-H.Y.), Mercer University School of Medicine, Savannah, Georgia 31404

Correspondence: Address all correspondence and requests for reprints to: Dr. Gary D. Hammer, Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, 1502 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109-2200. E-mail: ghammer{at}umich.edu.

Scientists have long hypothesized the existence of tissue-specific (somatic) stem cells and have searched for their location in different organs. The theory that adrenocortical organ homeostasis is maintained by undifferentiated stem or progenitor cells can be traced back nearly a century. Similar to other organ systems, it is widely believed that these rare cells of the adrenal cortex remain relatively undifferentiated and quiescent until needed to replenish the organ, at which time they undergo proliferation and terminal differentiation. Historical studies examining cell cycle activation by label retention assays and regenerative potential by organ transplantation experiments suggested that the adrenocortical progenitors reside in the outer periphery of the adrenal gland. Over the past decade, the Hammer laboratory, building on this hypothesis and these observations, has endeavored to understand the mechanisms of adrenocortical development and organ maintenance. In this review, we summarize the current knowledge of adrenal organogenesis. We present evidence for the existence and location of adrenocortical stem/progenitor cells and their potential contribution to adrenocortical carcinomas. Data described herein come primarily from studies conducted in the Hammer laboratory with incorporation of important related studies from other investigators. Together, the work provides a framework for the emerging somatic stem cell field as it relates to the adrenal gland.

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