HORMONALLY REGULATED COMPONENTS OF THE ADRENOCORTICAL CELL ENVIRONMENT AND THE CONTROL OF ADRENAL-CORTEX HOMEOSTASIS

The extracellular matrix (ECM) strongly contributes to the regulation of cell proliferation and cell differentiation, and thereby of embryon ic development and adult tissue homeostasis. We review here the ongoin g characterization of the structure and functions of the extracellular matrix components secreted by adrenocortical cells and discuss their possible implication in the hormonal regulation of adrenal cortex home ostasis. Fibronectin (FN) and laminin (LN) are both major adhesive pro teins for adrenocortical cells. FN is synthesized by bovine fasciculat a cells in primary culture, and its synthesis is stimulated by TGF bet a 1, TGF beta 2, and FGF-2 but is not modified by IGF-1 or by the horm ones ACTH and angiotensin II. LN is also synthesized by bovine fascicu lata cells and its synthesis is specifically stimulated by ACTH. Both proteins are haptotactic and chemotactic for adrenocortical cells, sug gesting a physiological role in adrenocyte migration. Their distributi on in the adrenal gland is quite distinct. LN is uniformly present in the steroidogenic cells from the three zones, whereas FN is abundant i n the fibrovascular structures of the capsule and the cortex. ACTH tre atment of adrenocortical cells strongly induces the expression and sec retion of thrombospondin-2 (TSP2), a large trimeric matricellular prot ein. The multimodular structure of TSP2 is the support of a variety of biological functions. TSP2 promotes attachment but prevents spreading of adrenocortical cells. On the other hand, TSP2 induces the activati on of latent TGF beta through an indirect mechanism and is anti-angiog enic in vitro. The overall distribution of TSP2 in the glomerulosa and fasciculata zones of the adrenal cortex, and its absence from the ret icularis zone, argue in favor of a role in the protection of adrenocor tical cells against apoptosis. In the adrenal cortex, five main biolog ical functions are potentially regulated by components of the extracel lular matrix: stem cell commitment into the adrenocyte differentiation pathway, terminal differentiation toward the three distinct adrenocyt e phenotypes, centripetal migration, apoptosis and the formation of th e capillary network. Future studies will aim at deciphering which extr acellular component(s) is involved in each of these regulations.