DHEA: the pathway in the body

DHEA is part of the pathway “DHEA”. This page shows the whole pathway; the station of DHEA is highlighted.

Where this laboratory value sits: DHEA — dehydroepiandrosterone. The same enzyme now cleaves off the side chain. This second activity needs the helper cytochrome b5, found mainly in the inner layer of the adrenal cortex. Source 2, 4

In brief

DHEA (dehydroepiandrosterone) is a steroid hormone made from cholesterol, mainly by the adrenal cortex. In the blood it is mostly present as DHEA sulfate; tissues convert it into testosterone and oestrogens.

The pathway step by step

1. Cholesterol → Pregnenolone CYP11A1 · StAR protein, NADPH The StAR protein moves cholesterol into the mitochondrion. There the enzyme CYP11A1 shortens the side chain, forming pregnenolone, the common precursor. Source 5, 1
2. Pregnenolone → 17-OH-pregnenolone CYP17A1 · NADPH CYP17A1 adds an OH group at position 17. The enzyme sits in the cell's endoplasmic reticulum and obtains its electrons from NADPH. Source 1
3. 17-OH-pregnenolone → DHEA CYP17A1 (lyase) · Cytochrome b5 The same enzyme now cleaves off the side chain. This second activity needs the helper cytochrome b5, found mainly in the inner layer of the adrenal cortex. Source 2, 4
4. DHEA → DHEA sulfate SULT2A1 · PAPS The enzyme SULT2A1 attaches a sulfate group. DHEA sulfate stays in the blood longer than DHEA itself and is the more abundant form there. Source 3
5. DHEA in tissues → Androstenedione 3β-HSD · NAD⁺ 3β-hydroxysteroid dehydrogenase converts DHEA into androstenedione. From here two pathways lead onwards. Source 1
6. Androstenedione → Testosterone 17β-HSD · NADPH A 17β-hydroxysteroid dehydrogenase replaces a keto group with an OH group. This forms testosterone. Source 1
7. Androstenedione → Estrone Aromatase · NADPH Aromatase reshapes the first ring of the molecule and removes a carbon atom in the process. Androstenedione becomes estrone. Source 1
8. Testosterone → Estradiol Aromatase · NADPH The same aromatase turns testosterone into estradiol. DHEA is therefore a starting material for both groups of sex hormones. Source 1, 3

Cofactors in this pathway

• NADPH — Electron donor for CYP11A1, CYP17A1 and aromatase Source 1
• Iron — Haem iron at the centre of CYP11A1, CYP17A1 and aromatase; iron-sulfur in adrenodoxin Source 1, 5In the ORY catalogue as a laboratory value: Eisen
• Cytochrome b5 — Partner of CYP17A1 in cleaving the side chain that yields DHEA Source 2, 4
• NAD⁺ — Accepts hydrogen at 3β-HSD when DHEA is converted to androstenedione Source 1In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Vitamin B2 (FAD, FMN) — Component of the reductases that pass electrons from NADPH to the steroid enzymes Source 1
• PAPS (active sulfate) — Provides the sulfate group that SULT2A1 attaches to DHEA Source 3

Sources

1. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011 · PubMed 21051590
2. Miller WL. Androgen synthesis in adrenarche. Rev Endocr Metab Disord 2009 · PubMed 18821018
3. Rainey WE, Nakamura Y. Regulation of the adrenal androgen biosynthesis. J Steroid Biochem Mol Biol 2008 · PubMed 17945481
4. Auchus RJ. The physiology and biochemistry of adrenarche. Endocr Dev 2011 · PubMed 21164255
5. Papadopoulos V, Miller WL. Role of mitochondria in steroidogenesis. Best Pract Res Clin Endocrinol Metab 2012 · PubMed 23168279

Whole pathway: DHEA

Related pathways

• Estradiol — cholesterol
• Testosterone — cholesterol
• Cholesterol and lipoproteins — cholesterol
• Cortisol — cholesterol
• Estrogen breakdown — estrone

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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