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Human embryonic mesodermal adrenogonadal progenitor cells, which give rise to the steroidogenic cells of the gonads and the adrenal cortex, first appear around the fourth week of gestation between the urogenital ridge and dorsal mesentery. The adrenal and gonadal cells then separate; the adrenal cells migrate retroperitoneally to the cranial pole of the mesonephros, and the gonadal cells migrate caudally. Between the seventh and eighth weeks of development, sympathetic neuroectodermal cells from the neural crest invade the primitive adrenal and become the adrenal medulla. By the end of the eighth week, the rudimentary adrenal has become encapsulated and is associated with the upper pole of the kidney, which at this time is much smaller than the adrenal.

The fetal adrenal cortex consists of an outer “definitive” zone, the principal site of glucocorticoid and mineralocorticoid synthesis, and a much larger “fetal” zone that makes androgenic precursors (dehydroepiandrosterone [DHEA] and DHEA sulfate [DHEAS]), which the placenta converts to estriol throughout pregnancy. A “transitional” zone exists between these regions toward the end of fetal development, but its functional role, if any, is unclear. At birth, the adrenals are about the same size of adult adrenals, weighing 8 to 9 g, and represent approximately 0.4% of total body weight. The large fetal adrenal zone involutes rapidly following birth and has disappeared by 6 to 12 postnatal months.

Unlike most other organs, the adrenal arteries and veins do not run in parallel. Arterial blood is provided by several small arteries arising from the renal and phrenic arteries, the aorta, and sometimes the ovarian and left spermatic arteries. The veins are more typical, with the left adrenal vein draining into the left renal vein and the right adrenal vein draining directly into the vena cava. Arterial blood enters the sinusoidal circulation of the cortex and drains toward the medulla, so that medullary chromaffin cells are bathed in very high concentrations of steroids. High concentrations of cortisol are required for expression of medullary phenylethanolamine-N-methyltransferase, which converts norepinephrine to epinephrine, linking the adrenal cortical and medullary responses to stress.

The adrenal cortex consists of 3 morphologically distinct zones: the glomerulosa, immediately below the capsule; the fasciculata, in the middle; and the reticularis, next to the medulla. These zones are distinct both functionally and histologically, but immunocytochemical data show that the zones physically interdigitate. The glomerulosa and fasciculate are not fully differentiated until about age 3 years, and the reticularis may not be fully differentiated until adolescence. The origin of the distinct adrenocortical zones and the mechanisms that regulate their proliferation are poorly understood.


The adrenal cortex produces 3 types of steroid hormones. Mineralocorticoids (aldosterone) regulate renal sodium retention, regulating electrolyte balance, intravascular volume, and blood pressure. Glucocorticoids (cortisol) are named for their carbohydrate-mobilizing activity, but regulate multiple bodily functions. Adrenal androgens serve no known physiologic role, but mediate some ...

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