Effects of chronic ACTH stimulation on the morphology of the rat adrenal cortex

The effects of chronic ACTH treatment (Depot Synacthen, 100 micrograms/day) on the morphology of the rat adrenal were studied in animals treated for 1 to 18 days. The gross weight of the adrenal increased up to tenfold, but although mitotic figures were seen after 3 days in the glomerulosa region, most of this is attributable to a vast increase in blood content. After 3 days of treatment the sinusoids in the reticularis became extremely dilated, and red blood cells penetrated the endothelial wall to become tightly packed around the cortical cells. This led to the gross distortion of the organization of the cortical tissue and after 7 days the cells in the reticularis region were isolated from each other by the continual infiltration of red blood cells. These changes gradually progressed outward so that other regions of the cortex became similarly affected. Eventually the cord-like arrangement of the fasciculata was disrupted. After 18 days of treatment, most of the cortex was involved and only a very thin layer of cells lying beneath the adrenal capsule was seemingly unaffected. Another major effect of corticotrophin treatment was the gradual loss of cellular differentiation, particularly of glomerulosa cells. Although the glomerulosa appeared normal after 1 day of treatment, cells of the fasciculata abut directly on the connective tissue capsule following 3 days of ACTH administration. Eventually glomerulosa cells disappeared almost completely, although there was no sign of cellular necrosis. It is likely that glomerulosa cells are transformed into fasciculata-type cells under ACTH treatment. This interpretation is consistent with functional changes that occur at the same time, including the loss of aldosterone synthetic capacity.