Overview:
The adrenal gland is structurally and functionally divided into the
outer cortex and inner medulla.
Cortex
– Embryologically derived from
mesoderm
– Produces
steroid hormones from cholesterol.
– The cortex can synthesize cholesterol de novo, but about 80% of the cholesterol used is obtained from circulating
LDLs.
– Each of the three layers of the adrenal cortex is regulated by
ACTH (adrenocorticotropin), though the outermost layer, the zona glomerulosa, is primarily regulated by
angiotensin II.
ACTH upregulates adrenocortical cell LDL receptors and increases enzymatic activity of cholesterol side chain cleavage, which releases cholesterol from the LDLs.
– Steroid hormones are metabolized in the liver, and secreted in the feces and urine.
Medulla
– Neural crest cell origins.
– Secretes catecholamines in response to
sympathetic nervous system stimuli (the adrenal medulla is sometimes called a specialized ganglion).
The adrenal gland receives substantial blood flow given its relatively small size.
The right and left adrenal glands are situated at the superior poles of the
kidneys (thus, their alternative name, "suprarenal glands").
We show the
aorta and renal arteries, and the
vena cava and the left renal vein.
Inferior phrenic arteries arise from the aorta and give rise to the
superior suprarenal arteries, which supply the superior regions of the adrenal glands.
Middle suprarenal arteries arise directly from the aorta and travel to the adrenal glands.
Inferior suprarenal arteries branch off the
renal arteries.
Venous drainage of the adrenal glands is asymmetrical:
– The right adrenal gland drains directly into the vena cava, but, because of its relative distance from the vena cava, the left adrenal gland first drains into the left renal vein.
Cortical hormones
These are the steroid hormones, which are regulated by ACTH.
Neurosecretory cells originate in the arcuate nucleus of the hypothalamus, and their axons terminate on capillaries of the
hypothalamic-pituitary portal system.
The hypothalamus secretes
Corticotropin-Releasing Hormone (CRH) into the neurosecretory cells.
When it reaches the anterior pituitary, CRH stimulates corticotrophin release of ACTH, which then travels in the blood to the adrenal cortex.
In response to ACTH, the adrenal cortex releases cortisol and androgens.
Regulation of Hypothalamic-Pituitary Axis:
At the hypothalamus: Hypoglycemia and stress trigger the release of CRH, whereas ACTH and Cortisol provide negative feedback.
– ACTH negative feedback on the hypothalamus represents a "short feedback" loop, whereas the cortisol negative feedback is a "long feedback" loop.
At the anterior pituitary gland: Cortisol provides negative feedback to inhibit the release of ACTH.
– This is the "short feedback" loop for cortisol.
Aldosterone: ACTH also stimulates aldosterone secretion – however, aldosterone secretion is primarily regulated by the renin-angiotensin II response to low renal blood pressure, and, by extracellular potassium concentrations.
– Thus, low renal blood pressure and elevated potassium levels stimulate aldosterone secretion.
Medulla hormones
The adrenal medulla is regulated by the sympathetic nervous system: preganglionic sympathetic fibers release acetylcholine on the chromaffin cells of the medulla, which triggers catecholamine release.
From outer to inner, show the capsule, cortex, and medulla.
Cortex
The cortex comprises three sub-layers, each with their own products:
Zona glomerulosa produces mineralocorticoids:
- Aldosterone regulates salt and water balance – thus, when you think of the zona glomerulosa layer, think: mineralo = Salt.
- *Zona fasciculata produces glucocorticoids:
– Cortisol regulates blood sugar – thus, when you think of the zona fasciculata, think: gluco = Sugar.
– This layer also produces a small quantity of androgens.
- *Zona reticularis produces androgens:
– Specifically, DHEA (dehydroepiandrosterone) and A4 (androstenedione), which regulate sex characteristics – thus, when you think of the zona reticularis, think: androgens = Sex.
– For completeness, indicate that this layer also produces a small quantity of glucocorticoids.
Medulla
Comprises the center of the adrenal gland, produces
norepinephrine and epinephrine – so, think medulla = Sympathetic nervous system.
Notice that we've indicated, from superficial to deep: Salt, Sugar, Sex, and Sympathetic regulation* (hence, the mnemonic "the deeper the sweeter" doesn't capture the full range of adrenal functions, it only describes the cortex!).
Capsule comprises fibrocollagen fibers and capillaries.
Zona glomerulosa comprises secretory cells with round nuclei arranged in irregular, rounded nests or clusters – aka, glomeruli.
– Indicate that these nests are separated by fibrous extensions of the capsule – these are the trabeculae.
– This is the thinnest layer of the cortex.
Zona fasciculata comprises columns or cords – aka, fascicles – of cells separated by collagen fibers and capillaries.
– These cells have abundant cytoplasm, which stains pale due to the presence of abundant lipid droplets.
– This is the widest layer of the cortex.
Zona reticularis comprises small branching cells that form a network – aka, reticulum – with capillaries.
– Because these cells have low lipid levels, they stain dark; indicate that you may see brown lipofuscin pigments in this layer.
Medulla comprises chromaffin, which are arranged in clusters around venous channels that deliver catecholamines to the blood.
For full references, please see our tutorial on the Adrenal Gland.
