Adrenocortical cells with stem/progenitor cell properties: recent advances

Abstract

The existence and location of undifferentiated cells with the capability of maintaining the homeostasis of the adrenal cortex have long been sought. These cells are thought to remain mostly quiescent with a potential to commit to self-renewal processes or terminal differentiation to homeostatically repopulate the organ. In addition, in response to physiologic stress, the undifferentiated cells undergo rapid proliferation to accommodate organismic need. Sufficient adrenocortical proliferative capacity lasting the lifespan of the host has been demonstrated through cell transplantation and enucleation experiments. Labeling experiments with tritium, BrdU, or trypan blue, as well as transgenic assays support the clonogenic identity and location of these undefined cells within the gland periphery. We define undifferentiated adrenocortical cells as cells devoid of steroidogenic gene expression, and differentiated cells as cells with steroidogenic capacity. In this review, we discuss historic developmental studies together with recent molecular examinations that aim to characterize such populations of cells.

Figure 1

Model of mammalian adrenal organogenesis detailing the sequential formation of the fetal zone, mesenchymal capsule and definitive zone followed by migration and differentiation of neural crest cells into chromaffin cells of the adrenal medulla and postnatal regression of the fetal zone.

Figure 2

Hypothetical model of stem and progenitor cell centripetal migration and differentiation into steroidogenically competent adrenocortical cells.

Figure 3

Summary cartoon of molecular events contributing to undifferentiated state of proposed adrenocortical progenitor cells (SF-1 +, Dax-1 +) and the role of inhibin as a gatekeeper of adrenocortical-specific differentiation of these cells (SF-1 +, Dax-1 −) in response to ACTH versus LH.