The secretion of cortisol is mainly controlled by three inter-communicating regions of the body, the hypothalamus in the brain, the pituitary gland and the adrenal gland . This is called the hypothalamic–pituitary–adrenal axis. When cortisol levels in the blood are low, a group of cells in a region of the brain called the hypothalamus releases corticotrophin-releasing hormone , which causes the pituitary gland to secrete another hormone, adrenocorticotropic hormone , into the bloodstream. High levels of adrenocorticotropic hormone are detected in the adrenal glands and stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to block the release of corticotrophin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary. As a result the adrenocorticotropic hormone levels start to drop, which then leads to a drop in cortisol levels. This is called a negative feedback loop.
Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandrosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.