21 Hydroxylase

 21-Hydroxylase is a key enzyme involved in the biosynthesis of adrenal steroid hormones, specifically glucocorticoids (like cortisol) and mineralocorticoids (like aldosterone). It is encoded by the CYP21A2 gene on chromosome 6p21.3, located in the HLA region.

Function of 21-Hydroxylase

• Catalyzes the hydroxylation at the 21st carbon of:

  1. Progesterone → 11-Deoxycorticosterone (DOC) → Aldosterone

  2. 17-Hydroxyprogesterone (17-OHP) → 11-Deoxycortisol → Cortisol

1950s – Identification of Congenital Adrenal Hyperplasia (CAH)

• 1950: Pediatric endocrinologists first describe infants with virilization, salt loss, and adrenal enlargement.

• These clinical observations led to the concept of adrenal enzyme defects.

• Early biochemical studies suggested an accumulation of 17-hydroxyprogesterone, pointing to a block in cortisol synthesis.

🔹 1960s – Discovery of the Enzymatic Defect

• Scientists began mapping the cortisol biosynthesis pathway, identifying various enzymatic steps.

• It was found that a deficiency in 21-hydroxylation (i.e., converting 17-hydroxyprogesterone to 11-deoxycortisol) explained the hormonal buildup and deficiency.

• This established 21-hydroxylase deficiency as the primary cause of the most common form of CAH.

Congenital Adrenal Hyperplasia History

1865 – First Clinical Description

• Luigi De Crecchio, an Italian physician, reported a case of a "hermaphrodite" who was genetically female but presented with male genitalia at autopsy.

• Though the term CAH wasn’t used, this was likely a case of classic 21-hydroxylase deficiency.

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