FRCA Notes


Adrenocortical Hormones

The curriculum asks for knowledge of 'adrenocortical hormones', which is about as succinct as it gets!


  • The adrenal cortex lies between the outer capsule and the inner medulla of the adrenal gland
  • Blood supply to the cortex arises from branches of capsular arteries
  • There is centripetal blood flow from these arteries, passing through the cortical zones and medulla to the medullary veins
  • The cortex is divided into three, distinct anatomical zones from outer to inner
    1. Zona glomerulosa: responsible for the production of mineralocorticoids (aldosterone)

    2. Zona fasciculata: responsible for the production of glucocorticoids (cortisol)

    3. Zona reticularis: responsible for the production of sex hormones (DHEA and androstenedione)

  • There are various acronyms for remembering this, including:
    • 'GFR' i.e. the order of the different zonae from outer to inner

    • 'Salt, sugar, sex - the deeper you go the sweeter it gets!' i.e. to remember the order of hormone production by the zones

Embryology

  • Adrenal hormones are vital for intra-uterine homeostasis and growth/maturation of organ systems
  • The foetal adrenal gland contains a large 'foetal zone' that produces DHEA-S and (less) cortisol
  • There is also a definitive (glomerulosa) and transitional (fasciculata) zone that later develop into adult structures
  • There is no foetal adrenal medulla or zona reticularis; these develop over 1.5yrs and 3-8yrs post-natally respectively

  • All steroids derive from cholesterol, which is transported into adrenal cells as LDL/HDL's
  • It is transported within adrenocortical cells to the mitochondria, where its side-chains are removed by the enzyme cholesterol desmolase
  • This is the rate-limiting step for production of all adrenal steroid hormones

  • The last common precursor is the 21-carbon molecule pregnenolone
  • Further biosynthesis depends upon the enzyme contents of the cell

Zona glomerulosa

  • Pregnenolone is metabolised to progesterone by 3β-hydroxysteroid dehydrogenase
  • Progesterone undergoes further hydroxylation and oxidation to aldosterone

Zona fasciculata

  • Here pregnenolone is also metabolised to progesterone by 3β-hydroxysteroid dehydrogenase
  • However, the enzyme metabolises progesterone to 17-hydroxyprogesterone
  • This undergoes hydroxylation steps to cortisol

Zona reticularis

  • Pregnenolone is acted upon directly by 17ɑ-hydroxylase, generating 17-hydroxypregnenolone
  • This undergoes lysis by 17,20-lyase to DHEA

  • Similarly to the zona fasciculata, pregnenolone also undergoes metabolism to 17-hydroxyprogesterone
  • Unlike the zona fasciculata, however, it instead too undergoes lysis by 17,20-lyase to androstenedione

  • Both DHEA and androstenedione undergo further metabolism (by both 3β- and 17β-hydroxysteroid dehydrogenase) to the sex hormones, testosterone and oestradiol