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The cells of the adrenal cortex are of mesodermal origin, in
contrast to the neuroectodermal cells of the adrenal medulla. Human
embryonic adrenogonadal progenitor cells first appear at around
the fourth week of gestation between the urogenital ridge and dorsal
mesentery. These progenitor cells give rise to the steroidogenic
cells of the gonads and to the adrenal cortex. 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
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.
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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], dehydroepiandrosterone
sulfate [DHEAS]), which the placenta converts
to estriol throughout pregnancy. A putative “transitional” zone exists
between these regions toward the end of fetal development, but its
functional role, if any, is unclear. At birth, the adrenals weigh
8 to 9 g, about the same size of adult adrenals, and represent approximately
0.4% of total body weight. The fetal adrenal zone involutes
rapidly following birth and has disappeared by 6 to 12 months of
postnatal life.
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Unlike most other organs, the arteries and veins serving the
adrenal 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.
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The adrenal cortex consists of three 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. After birth, the large fetal zone begins
to involute and disappears by about 6 to 12 months of age. The definitive
zone simultaneously enlarges, but the glomerulosa and fasciculate
are not fully differentiated until about 3 years of age, 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.
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The adrenal cortex produces three types of steroid ...