During stress, the adrenal medulla and zona fasciculata of the cortex can interact directly. Cortisol secretion from the zona fasciculata is controlled by circadian secretion of ACTH, the stress-induced stimulation of the HPA, and the negative feedback regulation of the HPA by cortisol. The adrenal cortex respond to the hypothalamic-pituitary axis (HPA) via corticotropic releasing factor (CRF) from the hypothalamus which causes the pituitary to secrete adrenocorticotropic hormone (ACTH) which acts on the zona fasciculata cells to produce cortisol. During stress cholesterol is converted to cortisol and the zona fasciculata decreases in size. Zona fasciculata cells, unlike the cells in the zona glomerulosa, possess the enzymes 17α-hydroxylase and 11β-hydroxylase, which promote the conversion of progesterone to cortisol. This layer has large, lipid-rich, polyhedral cells that store large amounts of cholesterol which is a precursor of cortisol. The middle layer of the adrenal cortex is the zona fasciculata which makes up about 80% of the mature adrenal cortex.
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