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

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. After ovulation, LH drives its formation.

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 · 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. Which hormone it becomes depends on the cell's enzymes. Source 1↑ supplies Pregnenolone is the starting point of all steroid hormones; which ones form depends on the cell's set of enzymes. In the corpus luteum the route leads mainly via 3β-HSD to progesterone. established physiology Source 1
   ⚖ When the balance tips

   too much — If more pregnenolone forms than 3β-HSD converts, CYP17A1 can turn it directly into 17-OH-pregnenolone and on to DHEA; the flow then shifts towards the androgens.

   too little — If little pregnenolone is available, all downstream steroid hormones are short of their starting material, because every route begins with this one step.

   established physiology · 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. In the corpus luteum, LH drives this route. Source 1↑ supplies Driven by LH, the corpus luteum makes much progesterone after ovulation; in pregnancy the placenta takes over. In the adrenal cortex it is mostly converted straight on to cortisol and aldosterone. established physiology Source 1
   ⚖ When the balance tips

   too much — If the corpus luteum makes much progesterone, more of it reaches the blood, and more progesterone receptors are occupied in the target tissue.

   too little — When the drive from LH fades, the corpus luteum regresses and progesterone formation falls; without pregnancy this happens at the end of every cycle.

   established physiology · Source 1, 2

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. For progesterone, this is an outflow. Source 1↓ depletes For progesterone this step is an outflow: CYP17A1 draws it towards cortisol and the sex hormones. Whether the lyase works besides the hydroxylase is set by helper proteins such as cytochrome b5. established physiology Source 1
   ⚖ When the balance tips

   too much — If CYP17A1 works strongly, more progesterone flows off to 17-OH-progesterone, and less remains as progesterone.

   too little — If CYP17A1 works little, progesterone builds up before it; more of it is then converted via CYP21A2 into mineralocorticoid precursors.

   established physiology · 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. Progesterone serves as a precursor here. Source 1↑ supplies Here progesterone provides the raw material for cortisol, androgens and estrogens; which hormone forms depends on the organ and its enzymes. established physiology Source 1
   ⚖ When the balance tips

   too much — If much precursor flows into this route, more cortisol or more androgen forms depending on the enzymes present; when cortisol rises, it slows ACTH release via the pituitary.

   too little — If little precursor arrives, less cortisol forms; the pituitary then releases more ACTH, and the adrenal cortex is driven harder.

   established physiology · 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. With much progesterone present, more receptors are occupied. Source 2↑ supplies Only the loaded receptor becomes active. PR-A and PR-B act differently: PR-B drives genes more strongly, PR-A can restrain PR-B; the ratio of the two shapes the tissue's response. established physiology Source 2
   ⚖ When the balance tips

   too much — If much progesterone is present, more receptors are occupied; occupied receptors are then broken down faster, so the response does not grow without limit.

   too little — If little progesterone is present, the receptors stay bound to their companion proteins and at rest; the genes concerned are read less often.

   established physiology · 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. This ends its action. Source 4↓ depletes Breakdown in the liver removes progesterone from the blood and ends its action. Progesterone arriving from the gut via the portal vein is largely broken down on its first pass. established physiology Source 4
   ⚖ When the balance tips

   too much — If much progesterone is circulating, more pregnanediol forms as well; its amount thus follows progesterone formation.

   too little — If the liver breaks it down more slowly, progesterone stays in the blood longer, and more of it reaches the target cells.

   established physiology · 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. This yields the precursor of allopregnanolone. Source 3↑ supplies This step uses up progesterone and provides the precursor of the neurosteroid allopregnanolone; it is regarded as the bottleneck of this route. In the brain, progesterone from the blood is also used for it. established physiology Source 3
   ⚖ When the balance tips

   too much — If much progesterone is present, more 5α-dihydroprogesterone forms via 5α-reductase, and in turn more allopregnanolone.

   too little — If 5α-reductase is inhibited, for example by finasteride, little 5α-dihydroprogesterone forms and allopregnanolone formation stalls; this is described in animal models.

   observed in studies · 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. In the uterine lining it thus controls the remodelling after ovulation. Source 2↑ supplies In the uterine lining, the receptor pair switches gene reading after ovulation: the lining stops growing and is remodelled for implantation. It also controls genes in the mammary gland. established physiology Source 2
   ⚖ When the balance tips

   too much — If the receptor stays occupied for long, the lining is held in its remodelled state; at the same time progesterone holds back the estrogen-driven cell division there.

   too little — When receptor occupancy falls away, the remodelled lining is no longer maintained and is shed; without pregnancy this is how menstruation begins.

   established physiology · 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. With this, progesterone finally leaves the circulation. Source 4↓ depletes The attached glucuronic acid makes the fat-soluble steroid water-soluble; only then can the kidney excrete it in the urine. established physiology Source 4
   ⚖ When the balance tips

   too much — If much pregnanediol is formed, more pregnanediol glucuronide passes into the urine as well.

   too little — If little UDP-glucuronic acid is available or the UGT works slowly, more pregnanediol stays unconjugated and is excreted more slowly.

   established physiology · 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. This makes the nerve cell harder to excite. Source 3↑ supplies At the GABA-A receptor, allopregnanolone amplifies the action of GABA: the chloride channel stays open longer, and the nerve cell becomes harder to excite. In large amounts it also opens the channel itself. observed in studies Source 3
    ⚖ When the balance tips

    too much — If much allopregnanolone is present, more GABA-A channels stay open; in animal models this markedly damps nerve cell excitability, with very large amounts up to anaesthesia.

    too little — If allopregnanolone falls quickly, for instance when progesterone formation ends, the GABA-A receptor loses this amplification; in animal models nerve cells then become easier to excite.

    observed in studies · Source 3

Further stations

• Cholesterol — origin of all steroids All steroid hormones derive from cholesterol. In the producing cells, the protein StAR carries it to the inner membrane of the mitochondria. How much of it arrives is controlled by LH and ACTH. Source 1↑ supplies Cholesterol is the raw material. The pace is set by StAR transport to the inner mitochondrial membrane; in the corpus luteum LH drives it, in the adrenal cortex ACTH, both via cAMP. established physiology Source 1
  ⚖ When the balance tips

  too much — If more cholesterol is ready in the cell, more progesterone does not form by itself: StAR transport into the mitochondria sets the pace, and LH and ACTH control it.

  too little — If little cholesterol reaches the inner mitochondrial membrane, for example when StAR does not work, the formation of all steroid hormones stalls at once; the cholesterol then collects in the cell's lipid droplets.

  established physiology · Source 1

• Progesterone in blood — bound to carrier proteins In the blood, progesterone is mostly bound to albumin and to the transport protein CBG. The unbound portion enters the cells. Only the free portion reaches the receptor. Source 1, 2↑ supplies Binding to albumin and CBG keeps a reserve in the blood; only the free portion reaches the receptor. Because the liver breaks it down quickly, progesterone stays in the blood only briefly. established physiology Source 1, 4
  ⚖ When the balance tips

  too much — If there is much progesterone in the blood, the free portion rises too; more enters the cells, and the liver breaks more of it down to pregnanediol.

  too little — If there is little progesterone in the blood, fewer molecules reach the cells, and the progesterone receptor is occupied less often.

  established physiology · Source 1, 2, 4

Cofactors in this pathway

• Cholesterol — Starting material from which CYP11A1 makes pregnenolone; without it no steroid hormone forms Source 1In the ORY catalogue as a laboratory value: Cholesterin / Fettstoffwechsel
• NADPH — Electron donor for CYP11A1, CYP17A1, 5α-reductase and 3α-HSD; without NADPH these steps stall Source 1, 3
• NAD⁺ — Hydrogen acceptor of 3β-HSD, which makes progesterone from pregnenolone; with little NAD⁺, this step stalls 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; without haem these enzymes do not work 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; without them no electron flow Source 5
• Zinc — Building block of the zinc fingers with which the progesterone receptor binds DNA; only then does it act on genes Source 6, 2In the ORY catalogue as a laboratory value: Zink
• UDP-glucuronic acid — Provides the glucuronic acid that a UGT attaches to pregnanediol and so makes it excretable 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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