The zona glomerulosa is under feedback control of the renin–angiotensin–aldosterone system. The juxtaglomerular cells in the kidney release renin in response to a decrease in blood pressure or a low blood sodium level. Circulating renin catalyzes the conversion of circulating angiotensinogen to angiotensin I, which in turn is converted by angiotensin-converting enzyme (ACE) in the lung to angiotensin II. Angiotensin II then stimulates the cells of the zona glomerulosa to secrete aldosterone. As the blood pressure, sodium concentration, and blood volume increase in response to aldosterone, the release of renin from the juxtaglomerular cells is inhibited. Drugs that inhibit ACE in the lung are effective in the treatment of chronic essential hypertension.
The cells of the zona fasciculata are large and polyhedral. They are arranged in long straight cords, one or two cells thick, that are separated by sinusoidal capillaries. The cells of the zona fasciculata have a lightly staining spherical nucleus. Binucleate cells are common in this zone. TEM studies reveal characteristics typical of steroid-secreting cells, i.e., a highly developed sER (more so than cells of the zona glomerulosa) and mitochondria with tubular cristae. They also have a well-developed Golgi apparatus and numerous profiles of rER that may give a slight basophilia to some parts of the cytoplasm (Fig. 21.24). In general, however, the cytoplasm is acidophilic and contains numerous lipid droplets, although it usually appears vacuolated in routine histologic sections because of the extraction of lipid during dehydration. The lipid droplets contain neutral fats, fatty acids, cholesterol, and phospholipids that are precursors for the steroid hormones secreted by these cells.
The principal secretion of the zona fasciculata is glucocorticoids that regulate glucose and fatty acid metabolism.
The zona fasciculata secretes glucocorticoids, so called because of their role in regulating gluconeogenesis (glucose synthesis) and glycogenesis (glycogen polymerization). One of the glucocorticoids secreted by the zona fasciculata, cortisol acts on many different cells and tissues to increase the metabolic availability of glucose and fatty acids, both of which are immediate sources of energy. Within this broad function, glucocorticoids may have different, even opposite effects in different tissues:  In the liver, glucocorticoids stimulate conversion of amino acids to glucose, stimulate the polymerization of glucose to glycogen, and promote the uptake of amino acids and fatty acids. In adipose tissue, glucocorticoids stimulate the break down of lipids to glycerol and free fatty acids. In other tissues, they reduce the rate of glucose use and promote the oxidation of fatty acids. In cells such as fibroblasts, they inhibit protein synthesis and even promote protein catabolism to provide amino acids for conversion to glucose in the liver.
Glucocorticoids also depress the immune and inﬂammatory responses and, as a result of the latter, inhibit wound healing. Hydrocortisone, a synthetic form of cortisol is used in treatment of allergies and inﬂammation. It depresses the inﬂammatory response by suppressing interleukin 1 (IL-1) and IL-2 production by lymphocytes and macrophages. Glucocorticoids also stimulate destruction of lymphocytes in lymph nodes and inhibit mitosis by transformed lymphoblasts. Cells of the zona fasciculata also secrete small amounts of gonadocorticoids, principally androgens.
ACTH regulates secretion of the zona fasciculata.