Adrenal gland & paraganglia


Histology-adrenal cortex

Topic Completed: 1 April 2013

Minor changes: 1 October 2021

Copyright: 2002-2021,, Inc.

PubMed Search: adrenal cortex [title] histology physiology "loattrfree full text"[sb]

Severino Rey Nodar, M.D., Ph.D.
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Cite this page: Nodar SR. Histology-adrenal cortex. website. Accessed December 3rd, 2021.
Definition / general
  • Synthesizes and secretes corticosteroids (mineralocorticoids, glucocorticoids and sex hormones), all derived from cholesterol
Essential features
  • Adrenal cortex has 3 layers
    • Zona glomerulosa (outer): produces mineralocorticoids (aldosterone - increases sodium and water absorption and potassium secretion)
    • Zona fasciculata (middle): produces glucocorticoids, some sex hormones
    • Zona reticularis (inner): produces estrogens and androgens, some glucocorticoids
  • Adrenal cortex anatomical zones ("gfr"):
    • Zona glomerulosa: secretes mineralocorticoids
    • Zona fasciculata: secretes glucocorticoids, lipid stores are depleted by ACTH
    • Zona reticularis: secretes androgens and small amounts of glucocorticoids
  • Glucocorticoids: raise blood glucose level; anti-inflammatory and immunosuppressive; cortisol release almost entirely controlled by ACTH secretion from anterior pituitary, controlled by corticotropin-releasing hormone (CRH) secreted by hypothalamus
  • Mineralocorticoids: aldosterone targets renal distal tubule and stimulates re-uptake of sodium and potassium; aldosterone accounts for 90% of mineralocorticoid activity, also deoxycorticosterone, corticosterone, cortisol
  • Androgens: includes testosterone; excessive production causes premature puberty in young boys and masculine pattern of body hair in females
  • Circulating low - density lipoproteins are internalized into cortical cells, lipoproteins are hydrolyzed, producing cholesterol esters, which break down to cholesterol and free fatty acids

    Cholesterol → 20 alpha hydroxycholesterol → (via 20, 22 desmolase complex)

          pregnenolone → progesterone - (21) → 11 deoxycorticosterone → corticosterone → aldosterone
             ↓(17)     ↓(17)
          17 alpha hydroxyprogesterone → (21) - deoxycortisol → cortisol
          dihydroxyepiandrosterone → androstenedione → estradiol 17 beta

    17=17 hydroxylase, 21=21 hydroxylase

  • Extraadrenal regulation
    • Hypothalamic corticotropin releasing hormone (CRH) enters hypophyseal portal system, reaches anterior pituitary gland and stimulates release of ACTH
    • ACTH travels in blood to adrenal cortex, is bound to cortical cell membranes and activates intracytoplasmic cyclases that form cAMP and GMP
    • Both cortisol and ACTH inhibit release of CRH, and cortisol also inhibits secretion of ACTH
    • ACTH normally is secreted episodically, with more and longer episodes in early morning and nadir in evening; this pattern causes circadian rhythm for cortisol seen in normals
    • Volume changes affect renin - angiotensin system, leading to aldosterone secretion
    • ACTH, potassium ions and aldosterone - stimulating factor also regulates aldosterone synthesis
  • Fetal adrenal gland lacks 3 beta hydroxysteroid dehydrogenase (converts pregnenolone to progesterone); as a result produces abundant dihydroepiandosterone, but little cortisol
Gross description
  • Normal cortex in adults is 2 mm thick
  • Zona reticularis is grossly brown in color
Microscopic (histologic) description
  • Zona glomerulosa:
    • Just beneath the adrenal capsule
    • Small clusters and short trabeculae of relatively small, well defined cells
    • Less cytoplasm than other cortical cells
    • Lipid poor
    • 15% of cortical volume
    Zona fasciculata:
    • Middle layer
    • Broad band of large cells with distinct membranes arranged in cords two cells wide
    • Cytoplasm has numerous small lipid vacuoles, which may indent the central nucleus and resemble lipoblasts
    • 70 - 80% of cortical volume
    Zona reticularis:
    • Innermost layer
    • Haphazardly arranged cells, smaller than zona fasciculata cells
    • Granular and eosinophilic cytoplasm with lipofuscin but minimal lipid
    • Thinner than zona glomerulosa or fasciculata
  • Richly vascularized, capsular blood vessels, nerves and lymphatics penetrate along connective tissue septae
  • Cortical extrusions: common into periadrenal fat, usually maintain attachment to adrenal gland
  • Cortical cuff: adrenal cortical cells around adrenal central vein and its branches
Microscopic (histologic) images

Contributed by Debra L. Zynger, M.D.
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Zona glomerulosa and fasiculata

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Zona fasiculata

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Zona fasciculata and reticularis

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Zona reticularis

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Zona reticularis with lipofuscin

Images hosted on other servers:

Reticularis lipid stain

Cortical layers

Cytology description
Cytology images

Contributed by Xiaoyin "Sara" Jiang, M.D.

Normal adrenal gland

Negative stains
Electron microscopy description
  • Zona glomerulosa: sparse intracellular lipid, elliptical mitochondria with lamellar (plate-like) cristae; may have microvillous projections; no / rare lysosomes, lipofuscin or smooth endoplasmic reticulum
  • Zona fasciculata: round / oval mitochondria with short and long tubular cristae; prominent lipid droplets, prominent smooth endoplasmic reticulum, moderate amounts of rough endoplasmic reticulum, microvillus cytoplasmic projections and more lysosomes than zona glomerulosa
  • Zona reticularis: spherical / ovoid mitochondria with short and long tubular invaginations of inner membrane; abundant lipofuscin granules, lysosomes and microvilli; sparse lipid droplets
Board review style question #1
    Which is the thickest layer of the adrenal cortex that is composed of large cells with pale cytoplasm and distinct cell membranes?

  1. Zona glomerulosa
  2. Zona fasiculata
  3. Zona reticularis
  4. Medulla
Board review style answer #1
B. Zona fasiculata

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Reference: Adrenal cortex
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