Progesterone: the pathway in the body

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

Progesterone is a steroid hormone formed from cholesterol, mainly in the corpus luteum and the placenta. Inside the cell it binds the progesterone receptor, and it is also the precursor of cortisol and the androgens.

The pathway step by step

1. Cholesterol → Pregnenolone CYP11A1 · NADPH The enzyme CYP11A1 cleaves off part of the side chain; NADPH supplies the electrons for this. Pregnenolone is the common precursor of all steroid hormones. Source 1
2. Pregnenolone → Progesterone 3β-HSD · NAD⁺ The enzyme 3β-HSD converts pregnenolone into progesterone. It is made mainly in the corpus luteum of the ovary, in the placenta and in the adrenal cortex. Source 1
3. Progesterone → 17-OH-progesterone CYP17A1 · NADPH The enzyme CYP17A1 attaches an OH group at position 17. From here the route branches off towards cortisol and the sex hormones. Source 1
4. 17-OH-progesterone → Other steroid hormones CYP21A2, CYP17A1 Further enzymes of the adrenal cortex and the gonads turn this into cortisol and androgens, and the androgens into estrogens. Source 1
5. Progesterone in blood → Progesterone receptor In the cell, progesterone binds to its receptor. The receptor detaches from companion proteins, changes shape and pairs up with another receptor. Source 2
6. Progesterone in blood → Pregnanediol Liver enzymes · NADPH In the liver, progesterone is saturated with hydrogen at several positions. The main product of this conversion is pregnanediol. Source 4
7. Progesterone in blood → 5α-dihydroprogesterone 5α-reductase · NADPH 5α-reductase transfers hydrogen to one ring of progesterone; NADPH supplies the electrons. This conversion takes place in the brain, among other tissues. Source 3
8. Progesterone receptor → Gene expression The receptor pair binds to specific DNA segments. Together with other proteins it regulates which genes are read there. Source 2
9. Pregnanediol → Pregnanediol glucuronide UGT · glucuronic acid A glucuronosyltransferase attaches glucuronic acid. In this water-soluble form, the substance leaves the body in the urine. Source 4
10. 5α-dihydroprogesterone → Allopregnanolone 3α-HSD · NADPH A 3α-hydroxysteroid dehydrogenase converts this into allopregnanolone. It attaches to the GABA-A receptor of the nerve cell and alters its behaviour. Source 3

Cofactors in this pathway

• Cholesterol — Starting material from which CYP11A1 makes pregnenolone Source 1In the ORY catalogue as a laboratory value: Cholesterin / Fettstoffwechsel
• NADPH — Electron donor for CYP11A1, CYP17A1, 5α-reductase and 3α-HSD Source 1, 3
• NAD⁺ — Hydrogen acceptor of 3β-HSD, which makes progesterone from pregnenolone Source 1In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Iron — Central atom in the haem of the cytochrome P450 enzymes of steroid formation Source 5, 1In the ORY catalogue as a laboratory value: Eisen
• Vitamin B2 (FAD, FMN) — Flavin cofactor of the reductases that pass electrons on to CYP11A1 and CYP17A1 Source 5
• Zinc — Building block of the zinc fingers with which the progesterone receptor binds DNA Source 6, 2In the ORY catalogue as a laboratory value: Zink
• UDP-glucuronic acid — Provides the glucuronic acid that a UGT attaches to pregnanediol Source 4

Sources

1. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011 · PubMed 21051590
2. Grimm SL, Hartig SM, Edwards DP. Progesterone Receptor Signaling Mechanisms. J Mol Biol 2016 · PubMed 27380738
3. Reddy DS. Neurosteroids: endogenous role in the human brain and therapeutic potentials. Prog Brain Res 2010 · PubMed 21094889
4. Stanczyk FZ. Pharmacokinetics of progesterone administered by the oral and parenteral routes. J Reprod Med 1999 · PubMed 11392023
5. Pinto JT, Cooper AJ. From cholesterogenesis to steroidogenesis: role of riboflavin and flavoenzymes in the biosynthesis of vitamin D. Adv Nutr 2014 · PubMed 24618756
6. Siegel KR, Kassotis CD. Friend and Foe?: Metals as Facilitators and Disruptors of Steroid Nuclear Receptor Signaling. Toxicol Sci 2026 · PubMed 42608812

Related pathways

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

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