Estradiol: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Estradiol (E2): which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Estradiol is the main oestrogen, a steroid hormone made from cholesterol. Aromatase forms it from testosterone; in the cell it binds the oestrogen receptor, which co-determines which genes are read.

The pathway step by step

1. Cholesterol → Pregnenolone CYP11A1 · NADPH, Oxygen The enzyme CYP11A1 shortens the side chain of cholesterol. It needs oxygen and electrons that come from NADPH. Source 1
2. Pregnenolone → DHEA CYP17A1 · NADPH, Cytochrome b5 CYP17A1 first attaches an OH group and then splits off two carbon atoms. This forms DHEA, a precursor of the sex hormones. Source 1
3. DHEA → Androstenedione 3β-HSD · NAD⁺ 3β-hydroxysteroid dehydrogenase converts DHEA, shifting a double bond in the ring system. Source 1
4. Androstenedione → Testosterone 17β-HSD · NADPH A 17β-hydroxysteroid dehydrogenase turns androstenedione into testosterone. Both substances are the direct precursors of the estrogens. Source 1
5. Testosterone → Estradiol Aromatase (CYP19A1) · NADPH, Oxygen Aromatase (CYP19A1) removes one carbon atom and turns the first ring into an aromatic ring. Testosterone thus becomes estradiol, and androstenedione becomes estrone. Source 2, 1
6. Estradiol in the blood → Estrogen receptor Inside the cell, estradiol binds to an estrogen receptor. Two receptors join to form a pair and bind to specific sections of DNA. Source 4
7. Estrogen receptor → Reading genes Together with other proteins, the receptor helps determine how strongly individual genes are read. Which genes these are depends on the tissue. Source 4
8. Estradiol in the blood → Estrone 17β-HSD type 2 · NAD⁺ A 17β-hydroxysteroid dehydrogenase converts estradiol into estrone. The reaction runs in both directions; the tissue determines which one prevails. Source 1, 5
9. Estrone → 2-Hydroxyestrone CYP1A1, CYP1B1 · NADPH Enzymes of the cytochrome P450 family, mainly CYP1A1 and CYP1B1, attach an OH group to the aromatic ring. Source 5
10. 2-Hydroxyestrone → 2-Methoxyestrone COMT · SAM, Magnesium Catechol-O-methyltransferase (COMT) attaches a methyl group. It comes from SAM, the methyl group donor of the cell. Source 5
11. 2-Methoxyestrone → Conjugates UGT, SULT Transferases couple the breakdown products to glucuronic acid or sulfate. Now water-soluble, they leave the body via urine and bile. Source 5

Cofactors in this pathway

• NADPH — Electron donor for CYP11A1, CYP17A1 and aromatase Source 1, 2
• Iron — Central atom of the haem in the cytochrome P450 enzymes involved Source 1In the ORY catalogue as a laboratory value: Eisen
• NAD⁺ — Accepts hydrogen at 3β-HSD and at 17β-HSD type 2 Source 1In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• SAM (from methionine) — Methyl group donor of COMT when catechol oestrogens are converted Source 5In the ORY catalogue as a laboratory value: Methionin
• Magnesium — Ion in the active site of COMT, which methylates catechol oestrogens Source 5In the ORY catalogue as a laboratory value: Magnesium
• Zinc — Keeps the two zinc fingers in the DNA-binding part of the oestrogen receptor in shape Source 7In the ORY catalogue as a laboratory value: Zink

What acts on this pathway

• Aromatase inhibitors — Anastrozole attaches to aromatase and blocks it; as a result, the body forms less estradiol. The earlier steps of the pathway are not affected. Source 6

Sources

1. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011 · PubMed 21051590
2. Simpson ER, Mahendroo MS, Means GD et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994 · PubMed 8076586
3. Hammond GL. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol 2016 · PubMed 27113851
4. Heldring N, Pike A, Andersson S et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007 · PubMed 17615392
5. Thomas MP, Potter BV. The structural biology of estrogen metabolism. J Steroid Biochem Mol Biol 2013 · PubMed 23291110
6. Cuzick J. Anastrozole. Drugs Today (Barc) 2005 · PubMed 16034487
7. Arao Y, Korach KS. The physiological role of estrogen receptor functional domains. Essays Biochem 2021 · PubMed 34028522

Related pathways

• DHEA — cholesterol
• Testosterone — cholesterol
• Estrogen breakdown — estradiol
• Cholesterol and lipoproteins — cholesterol
• Cortisol — cholesterol

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