Adrenocortical zonation and the adrenal renin-angiotensin system

The origins of mammalian adrenocortical zonation and the factors that maint ain it are poorly understood. We have examined the roles of the tissue reni n-angiotensin system and other paracrine morphogens and growth factors, and of specific transcription factors in adrenocortical cellular proliferation and development. From the data obtained, we propose a hierarchy of potenti al tissue modeling agents. These include morphogens, such as angiotensin II derived from an intraadrenal origin, growth factors, for example insulin-l ike growth factor-I, which can be considered to be the paracrine amplifiers of the morphogenic signal and finally transcription factors, such as c-fos and c-jun, that directly stimulate mitosis and other events of differentia tion. In particular, transcription of representative genes in all three cat egories is increased in the glomerulosa by a low sodium diet, correlated wi th its hypertrophy and increased aldosterone synthase. Corticotrophin treat ment tends to eliminate these indices of zonal differentiation. The adrenal cortex can also set up electrochemical gradients in response to stimulation. We postulate that the electrochemical gradient informs adreno cortical cells of their position within the gland, and may also facilitate "directed diffusion" of other morphogenic paracrine factors to precise loca tions of action.