EXPRESSION OF LAMININ AND ITS POSSIBLE ROLE IN ADRENAL-CORTEX HOMEOSTASIS

The adult mammalian adrenal cortex undergoes permanent regeneration. T his process implies a cellular proliferation step restricted to the ex ternal zone of the tissue, and a subsequent centripetal cell migration during which phenotypic transition from glomerulosa into fasciculata and reticularis cells and elimination of senescent cells through apopt osis occur. As the molecular mechanisms implied in adrenocortical cell migration are still generally unknown, we addressed that question in the present study. Of several extracellular matrix proteins tested, la minin was the most potent chemotactic and haptotactic factor for bovin e fasciculata adrenocortical cells. The maximal chemotactic effect (3- fold stimulation) was observed with 50-75 mu g/ml laminin, whereas the haptotactic effect (3.5-fold stimulation) plateaued for laminin conce ntrations in the coating solution over 25 mu g/ml. Using an anti-Engel breth-Holm-Swarm laminin antibody, we could demonstrate that adrenocor tical cells actively synthesize and secrete Engelbreth-Holm-Swarm-lami nin, with the A chain produced in limiting quantities. ACTH treatment of adrenocortical cells specifically induced a 2.7- to 4.5-fold increa se in A chain synthesis, resulting in a corresponding increase in the amount of secreted laminin. The distribution of laminin in the adrenal cortex tissue was then evaluated by standard immunohistochemistry. Th e protein appeared to be uniformly expressed in the three zones of the cortex. This observation does not favor the hypothesis that laminin a cts as an attractant driving centripetal cell migration. Laminin, whic h is synthesized under the control of the systemic hormone ACTH, appea rs as a permissive factor that facilitates proper homeostasis of the a drenocortical tissue.