Further Cytophysiologic Evidence for the Identity of the Cells That Produce Adrenocorticotrophic Hormone¹

Abstract

To provide further evidence for the identification of the cell type responsible for the production of adrenocorticotrophin (ACTH), the effects of acute and chronic administration of cortisol on the cells of the pituitaries of intact and adrenalectomized rats were studied by electron microscopy. Hypertrophied ACTH-cells, previously described as adrenalectomy-cells, were scarce in controls and became more numerous after adrenalectomy. Adrenalectomy-cells are characterized by their secretory granules, which are dense, sparse, and measure 200 μn or more in maximal diameter, and by the irregularity of their cell outlines, determined by their interior position in the cell cords and their tendency to send processes of cytoplasm around neighboring cells toward the capillaries. Normal ACTH-cells are identified by similar criteria, although they are less voluminous and their cell outlines tend to be less complex and varied. Acute administration of cortisol caused a striking accumulation of secretory granules in both adrenalectomy-cells of adrenalectomized rats and ACTH-cells of intact rats, while the morphology of the other cell types was not observably changed. In the animals treated with cortisol for one week, gonadotrophs and thyrotrophs were abundant and possessed organelles indicative of secretory activity, and somatotrophs appeared intensely stimulated, while the development of adrenalectomy-cells following adrenalectomy was prevented. Administration of 5 mg cortisol/100 g body weight daily for one week virtually eliminated normal ACTH-cells. The accumulation of granules in adrenalectomy-cells and ACTH-cells after acute administration of cortisol correlates with the increase of the pituitary content of ACTH reported for this time interval, while the diminution of these cells after one week of cortisol administration is consistent with the depression of ACTH stores known to follow this chronic treatment. These findings confirm our original identification of the adrenalectomy-cell as the site of ACTH secretion, and show that the cell identified in intact rats by the same criteria is the site of production of ACTH in normal rats. (Endocrinology86: 451, 1970)