DHEA: the pathway in the body · Biomarker & Blood Analysis

This page shows the biochemical pathway behind the laboratory value DHEA: 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

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. ACTH drives its production; the sulfate serves as a reserve.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

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. All steroid hormones branch off from here. Source 5, 1↑ supplies Pregnenolone is the switch point of all steroid hormones: depending on a cell's enzymes, it is built on into cortisol, aldosterone or, via CYP17A1, into DHEA. CYP11A1 needs electrons from NADPH for this. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot of pregnenolone forms, it is distributed over the routes open in the respective layer of the adrenal cortex; in the inner layer, rich in cytochrome b5, one of them leads to DHEA.

   too little — If little pregnenolone is available, less supply reaches all following steroid hormones at once, DHEA included, because each is built from this one precursor.

   established physiology · Source 1, 3

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. From here the route leads to cortisol or to DHEA. Source 1↑ supplies 17-OH-pregnenolone stands at a switch point: via 3β-HSD the route leads towards cortisol; if plenty of cytochrome b5 is present, CYP17A1 cleaves off the side chain with its 17,20-lyase activity, and DHEA forms. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — If 17-OH-pregnenolone builds up, the cell's enzymes decide its route: in the inner cortical layer, with little 3β-HSD and plenty of cytochrome b5, more of it becomes DHEA.

   too little — If CYP17A1 forms little 17-OH-pregnenolone, pregnenolone flows into the route without this step; more aldosterone precursors and less DHEA and cortisol are formed.

   established physiology · Source 2, 3, 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. DHEA is above all a precursor of sex hormones. Source 2, 4↑ supplies DHEA is itself a weak androgen and above all a precursor: tissues convert it into testosterone and oestrogens. How much forms is set by ACTH and by the lyase activity of CYP17A1, which cytochrome b5 increases. established physiology Source 2, 3, 1
   ⚖ When the balance tips

   too much — If the adrenal gland makes a lot of DHEA, most of it becomes DHEA sulfate via SULT2A1; more DHEA then means more starting material for conversion into androgens in the tissues.

   too little — If little cytochrome b5 is present or ACTH drives little, CYP17A1 cleaves the side chain less often; less DHEA forms, and 17-OH-pregnenolone tends towards cortisol.

   established physiology · Source 3, 2

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. It thus forms a long-lasting reserve. Source 3↕ both, depending on amount DHEA sulfate is the stable storage form: the sulfate group withdraws DHEA from direct conversion but keeps it in the blood for a long time as a reserve, from which tissues release it again with steroid sulfatase. established physiology Source 3, 1
   ⚖ When the balance tips

   too much — If a lot of DHEA is sulfated, the reserve in the blood grows; how much of it passes into androgens and oestrogens is then set by the sulfatase and the enzymes in the tissues.

   too little — If SULT2A1 attaches little sulfate, for example because little PAPS is available, more DHEA stays unsulfated and is more readily available for conversion to androstenedione and on to androgens.

   established physiology · Source 3, 1

5. DHEA in tissues → Androstenedione 3β-HSD · NAD⁺ 3β-hydroxysteroid dehydrogenase converts DHEA into androstenedione. From here two pathways lead onwards. Which route prevails depends on the enzymes in the tissue. Source 1↑ supplies Androstenedione is the switch point in the tissue: 17β-HSD turns it into testosterone, aromatase into estrone. Which direction prevails depends on which of these enzymes a tissue carries; 3β-HSD needs NAD⁺ to form it. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot of androstenedione forms, 17β-HSD and aromatase have more starting material; in tissues with plenty of aromatase, such as fat tissue, more estrone then forms.

   too little — If little androstenedione is available, less supply reaches testosterone and estrone in the tissue at once, because both are built from this intermediate.

   established physiology · Source 1

6. Androstenedione → Testosterone 17β-HSD · NADPH A 17β-hydroxysteroid dehydrogenase replaces a keto group with an OH group. This forms testosterone. It acts through the androgen receptor. Source 1↑ supplies Testosterone acts through the androgen receptor and is also a precursor: in some tissues 5α-reductase converts it into the more potent dihydrotestosterone, in others aromatase converts it into estradiol. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot of testosterone forms, more of it acts at the androgen receptor, and tissues with aromatase at the same time convert more of it into estradiol.

   too little — If little testosterone forms from DHEA, the tissues depend more on testosterone from the gonads; tissues with aromatase then also form less estradiol from it.

   established physiology · 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. It is a weak oestrogen. Source 1↑ supplies Estrone is a weak oestrogen and also a precursor: 17β-HSD can convert it into estradiol. Via aromatase, oestrogen thus also forms where no ovaries make it, for example in fat tissue. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot of estrone forms, for example in tissues with plenty of aromatase, more starting material is available from which 17β-HSD makes estradiol on site.

   too little — If aromatase works poorly, less estrone forms, and androstenedione tends to stay on the route to the androgens.

   established physiology · 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. It acts through the oestrogen receptors. Source 1, 3↑ supplies Estradiol is the most potent of the body's own oestrogens and acts through the oestrogen receptors. When DHEA from the blood is converted into estradiol, it forms in the tissue itself and acts there on site. established physiology Source 1
   ⚖ When the balance tips

   too much — If a tissue makes a lot of estradiol from testosterone, more oestrogen acts at the receptors there, and less testosterone remains.

   too little — If aromatase works poorly, more testosterone remains, and less estradiol acts at the oestrogen receptors in the tissue.

   established physiology · Source 1

Further stations

• Cholesterol — starting material All steroid hormones derive from cholesterol. In the adrenal cortex it is kept ready, stored in droplets. Its route into the mitochondrion sets the pace. Source 5↑ supplies Cholesterol is the raw material for DHEA as for all steroid hormones. How much of it enters production is set not by the store but by its transport into the mitochondrion, which ACTH sets in motion. established physiology Source 5, 1
  ⚖ When the balance tips

  too much — If plenty of cholesterol is stored in the droplets, more DHEA does not form by itself: the pace is set by transport into the mitochondrion through the StAR protein.

  too little — If little cholesterol gets into the mitochondrion, for example because StAR works poorly, production of all steroid hormones stalls at once, and cholesterol accumulates in the cortical cells.

  established physiology · Source 5

• DHEA in tissues — sulfate removed again In tissues such as skin, fat or the gonads, steroid sulfatase removes the sulfate again. Only then can DHEA be converted further. This turns the reserve back into starting material. Source 3, 1↑ supplies Only steroid sulfatase makes the reserve from the blood usable: it releases DHEA in the cell, which then converts it itself into androgens or oestrogens. In this way each tissue helps determine how much hormone forms within it. established physiology Source 1, 3
  ⚖ When the balance tips

  too much — If steroid sulfatase is highly active in a tissue, more DHEA is released there from the sulfate and converted on site into androgens and oestrogens.

  too little — If steroid sulfatase works poorly, more DHEA stays bound as sulfate; the tissue then has less free DHEA for its own conversion.

  established physiology · Source 1

Cofactors in this pathway

• NADPH — Electron donor for CYP11A1, CYP17A1 and aromatase; without it every step stalls Source 1
• Iron — Haem iron at the centre of CYP11A1, CYP17A1 and aromatase; iron-sulfur in adrenodoxin; no haem, no conversion Source 1, 5In the ORY catalogue as a laboratory value: Eisen
• Cytochrome b5 — Partner of CYP17A1 in cleaving the side chain that yields DHEA; shifts the route towards DHEA Source 2, 4
• NAD⁺ — Accepts hydrogen at 3β-HSD when DHEA is converted to androstenedione; without it no 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; without FAD the flow stalls Source 1
• PAPS (active sulfate) — Provides the sulfate group that SULT2A1 attaches to DHEA; this forms the reserve in the blood 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

Related pathways

• Estradiol — cholesterol
• Testosterone — cholesterol
• Cholesterol and lipoproteins — cholesterol
• Cortisol — cholesterol
• Progesterone — cholesterol

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
Legal notice Privacy policy All biomarkers