Prednisolon: the pathway in the body

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

Where this laboratory value sits: Prednisolone — active form, OH group. In the body prednisone is converted completely into prednisolone. Between the keto and the OH form the enzymes 11β-HSD1 and 11β-HSD2 switch back and forth; the same enzymes also interconvert cortisone and cortisol. 11β-HSD2 converts it back to the keto form. Source 4, 11

In brief

Prednisolone is a synthetic glucocorticoid. It blocks nothing — it binds the same receiver as the body's own cortisol and switches it on. The receptor moves into the cell nucleus and helps govern the reading of many genes. Through the feedback, ACTH release falls.

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. Prednisone → Prednisolone 11β-HSD1 In the body prednisone is converted completely into prednisolone. Between the keto and the OH form the enzymes 11β-HSD1 and 11β-HSD2 switch back and forth; the same enzymes also interconvert cortisone and cortisol. 11β-HSD2 converts it back to the keto form. Source 4, 11↑ supplies Prednisolone is the form that switches the glucocorticoid receptor on. 11β-HSD2, for instance in the kidney, can convert it back to the keto form and so keep it away from certain tissues. established physiology Source 4
   ⚖ When the balance tips

   too much — If a lot of prednisolone is present, it occupies the glucocorticoid receptor in many tissues at once, and through the feedback the release of CRH and ACTH falls.

   too little — If little prednisolone is present, it occupies only part of the receptors; the body's own cortisol then determines a larger share of the signals.

   established physiology · Source 1, 2

2. Prednisolone → In the blood In the blood part of the substance is bound to the carrier protein CBG and to albumin. CBG also carries the body's own cortisol; only the unbound part passes into the cells. CBG acts as a store in the blood. Source 5↑ supplies The carrier protein CBG holds a store in the blood and releases substance when the unbound part moves into the cells. Only the free part reaches the receptor. established physiology Source 5
   ⚖ When the balance tips

   too much — If there is a lot of prednisolone in the blood, the binding sites on CBG are soon occupied; the free part then grows faster than the total amount.

   too little — If there is little CBG in the blood, a larger part of prednisolone and cortisol is unbound and passes more easily into the cells.

   established physiology · Source 5

3. In the blood → Broken down in the liver The liver converts prednisolone further. The breakdown products leave the body with the urine, there as sulfate and glucuronide compounds. This ends the action at the receptor. Source 11↓ depletes Breakdown in the liver ends the action: the breakdown products are coupled to sulfate or glucuronic acid, thus made water-soluble and excreted via the kidneys. established physiology Source 11
   ⚖ When the balance tips

   too much — If the liver breaks it down quickly, prednisolone leaves the blood sooner, and the receptor becomes free again earlier.

   too little — If the liver breaks it down more slowly, prednisolone stays in the blood longer and occupies the receptor for longer.

   established physiology · Source 11

4. At the receptor → In the cell nucleus · Hsp90 lets go With the substance bound, the receptor lets go of the helper proteins and moves into the cell nucleus. There it settles on certain stretches of DNA and also damps other gene switches such as NF-κB and AP-1. Inflammatory genes are thus damped. Source 1↓ depletes In the cell nucleus the receptor mainly damps: it binds NF-κB and AP-1 and so slows the reading of genes for inflammatory messengers; it also switches on genes for damping proteins. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot of receptor is active in the nucleus, genes for inflammatory messengers are slowed in many cell types at once; immune cells then also make fewer of these signalling substances.

   too little — If little receptor is active in the nucleus, NF-κB and AP-1 run with less restraint, and genes for inflammatory messengers are read more often.

   established physiology · Source 1

5. In the cell nucleus → Gene reading By this route the receptor acts on the reading of numerous genes — in the immune system, in intermediary metabolism, in the gut wall and in bone. In the liver more glucose then forms. Source 1, 7↑ supplies Through the reading of many genes the receptor makes energy available: in the liver more glucose forms from amino acids, and muscle and fat tissue release building blocks for it. established physiology Source 1
   ⚖ When the balance tips

   too much — If gene reading stays at a high level for long, the liver makes more glucose, muscle protein is broken down, and fewer new osteoblasts mature in bone.

   too little — If it is low, the liver makes less glucose during fasting, and inflammatory signals are slowed less.

   observed in studies · Source 1, 7

6. CRH → ACTH CRH receptor CRH reaches the pituitary gland through fine blood vessels. There it binds its receptor and triggers the release of the hormone ACTH into the blood. ACTH also maintains the tissue of the adrenal cortex. Source 2↑ supplies ACTH stimulates the adrenal cortex to make cortisol and at the same time maintains its cortisol-forming tissue. established physiology Source 2, 3
   ⚖ When the balance tips

   too much — If a lot of ACTH is present, the adrenal cortex makes more cortisol, and its cortisol-forming cells increase in size and number.

   too little — If little ACTH is present over a longer period, for instance because glucocorticoids engage the feedback, the adrenal cortex makes less cortisol, and its cortisol-forming tissue becomes thinner.

   established physiology · Source 2, 3

7. ACTH → The body's own cortisol MC2 receptor ACTH binds the receptor MC2R in the adrenal cortex. The cortex then converts cholesterol over several steps into cortisol and releases it into the blood. Cortisol in turn damps CRH and ACTH. Source 2↑ supplies The body's own cortisol binds the same receptor as prednisolone and follows a daily rhythm; at the same time it damps CRH and ACTH through the feedback. established physiology Source 2, 1
   ⚖ When the balance tips

   too much — If a lot of cortisol is present, it damps the release of CRH and ACTH in the hypothalamus and pituitary gland until the level falls again.

   too little — If the adrenal cortex makes little cortisol of its own, for instance because ACTH is damped, the action at the receptor comes mainly from the prednisolone present.

   established physiology · Source 2, 1

8. Calcium from food → TRPV6 in the gut wall TRPV6 · calcitriol The channel TRPV6 leads calcium into the gut cell. How much of it is made is governed by calcitriol — the active form of vitamin D — through the cell nucleus. Calbindin binds the calcium at once. Source 8↑ supplies TRPV6 is the gate for active calcium uptake in the duodenum: the more channels the cell makes, the more calcium enters. Less TRPV6 is described in mice under prednisolone. observed in studies Source 8, 6
   ⚖ When the balance tips

   too much — If the gut cell makes many TRPV6 channels, more calcium enters; calbindin binds it at once so that the free calcium level in the cell stays low.

   too little — If the gut cell makes few TRPV6 channels, as described in mice under prednisolone, less calcium enters by this active route.

   observed in studies · Source 8, 6

9. TRPV6 in the gut wall → Calcium in the blood calbindin, PMCA1b Calbindin carries calcium through the cell, the pump PMCA1b hands it to the blood. In experiments in mice, TRPV6 and calbindin in the duodenum were present at lower levels under prednisolone; the label also states a greater output of calcium with the urine. Source 6, 8, 11↑ supplies Calcium in the blood supplies bone, nerves and muscles; part of it passes via the kidneys into the urine. The label states a greater output of calcium with the urine under glucocorticoids. established physiology Source 8, 11
   ⚖ When the balance tips

   too much — If blood calcium rises, parathyroid hormone release falls, less calcitriol forms, and the gut absorbs less calcium.

   too little — If blood calcium falls, parathyroid hormone release rises; more calcitriol forms, the gut makes more TRPV6, and calcium is released from bone.

   established physiology · Source 8

10. Osteocytes → Osteoblasts · sclerostin, Wnt system Sclerostin damps the Wnt system, through which osteoblasts mature from precursor cells. It is described that glucocorticoids damp maturation, activity and survival of osteoblasts. They replace bone mass that has been removed. Source 7↑ supplies Osteoblasts build new bone mass and replace what has been removed. Glucocorticoids are described as damping their maturation, activity and lifespan. observed in studies Source 7
    ⚖ When the balance tips

    too much — If many osteoblasts are active, more new bone mass is built than the bone-resorbing cells remove.

    too little — If few osteoblasts are active, for instance because glucocorticoids damp their maturation and survival, bone mass that has been removed is replaced more slowly.

    observed in studies · Source 7

Further stations

• Prednisone — keto form, the precursor Prednisone carries a keto group at one place of the molecule. In that form it does not yet act at the receptor. Prednisolone itself is swallowed as a tablet or a solution; glucocorticoids are absorbed rapidly from the gut. Only prednisolone acts. Source 10, 11↑ supplies Prednisone is a precursor: only after conversion into prednisolone, mainly in the liver, does it act at the receptor. It thus provides the store from which the active form arises. established physiology Source 11, 4
  ⚖ When the balance tips

  too much — If a lot of prednisone is present, 11β-HSD1 converts a correspondingly large amount into prednisolone, which then occupies the receptor.

  too little — If little prednisone is present or 11β-HSD1 works slowly, less prednisolone forms, and less action reaches the receptor.

  established physiology · Source 4, 11

• At the receptor — glucocorticoid receptor Without a hormone the glucocorticoid receptor sits in the cell plasma, bound to helper proteins such as Hsp90. Prednisolone is fat-soluble, passes through the cell membrane and binds the same pocket as cortisol. It switches the receptor on like cortisol. Source 1↑ supplies At the receptor prednisolone acts as a switch, not as an inhibitor: it occupies the place of cortisol and sets off the same chain as the body's own hormone. established physiology Source 1, 11
  ⚖ When the balance tips

  too much — If many receptors are occupied, the cell reduces the number of its glucocorticoid receptors over time; the same amount of hormone then triggers a weaker signal.

  too little — If few receptors are occupied, most of them stay bound to Hsp90 in the cell plasma, and the genes they govern are read at their baseline level.

  established physiology · Source 1

• CRH — hypothalamus Nerve cells in the hypothalamus release the hormone CRH. It is the first step of the axis that links hypothalamus, pituitary gland and adrenal cortex. Prednisolone damps its release through the feedback. Source 2↑ supplies CRH is the starting signal of the axis: it makes the pituitary gland release ACTH. Glucocorticoids, prednisolone included, damp its release through the feedback. established physiology Source 2
  ⚖ When the balance tips

  too much — If a lot of CRH is released, the pituitary gland releases more ACTH, and the adrenal cortex makes more cortisol until this damps the release again.

  too little — If little CRH is released, for instance because prednisolone engages the feedback, ACTH release falls, and the adrenal cortex receives less stimulus.

  established physiology · Source 2

• Osteocytes — cells inside the bone All bone cells carry the glucocorticoid receptor. For osteocytes it is described that glucocorticoids make them release more sclerostin. Sclerostin damps bone formation. Source 7↓ depletes In osteocytes the glucocorticoid receptor makes more sclerostin arise; this messenger damps bone formation in the surroundings. observed in studies Source 7
  ⚖ When the balance tips

  too much — If osteocytes release a lot of sclerostin, the Wnt system of the osteoblasts is damped more strongly, and fewer new bone-forming cells mature.

  too little — If osteocytes release little sclerostin, the Wnt system runs more freely, and osteoblasts mature more easily.

  observed in studies · Source 7

• Calcium from food — dissolved in the gut Calcium is present in food as a salt and dissolves in the upper digestive tract. Only dissolved calcium reaches the gut wall. Some passes passively between the cells. Source 8↑ supplies Dissolved calcium is the starting material for uptake in the gut wall; some passes passively between the cells, especially when a lot is dissolved. established physiology Source 8
  ⚖ When the balance tips

  too much — If a lot of calcium is dissolved, the gut absorbs a larger part passively between the cells; the route via TRPV6 then plays a smaller role.

  too little — If little calcium is dissolved, uptake depends more on the route via TRPV6 and calbindin, which calcitriol up-regulates.

  established physiology · Source 8

What this active substance affects

• Cortisol — Binds the same receptor; through the feedback, hypothalamus and pituitary form less CRH and ACTH Source 1, 2, 3
• Calcium — In the gut wall, less TRPV6 and calbindin are described under prednisolone — the proteins that let calcium in Source 6, 8
• Potassium — The label states a slight mineralocorticoid action: more sodium into the cells, less potassium inside them Source 11
• Sodium — The same mineralocorticoid action lets more sodium enter the cells, according to the label Source 11

What takes part in these steps

• Vitamin D — Calcitriol, the active form, governs the making of TRPV6 and calbindin in the gut wall; thus governs calcium uptake Source 8
• Zinc — Building block of the two zinc fingers with which the glucocorticoid receptor binds the DNA; without them no DNA binding Source 9, 1

What the prescribing information states

The prescribing information for this substance comes from an older labelling format. It lists the reported reactions by organ system and gives neither frequencies nor a comparator or placebo group. The table therefore only repeats what stands there under each heading.

How to read this table: it holds no figures, because the label gives none. Without a comparison group it cannot be said how often a reaction occurs, nor whether it would be rarer without the substance — the list only says what was reported, ordered by organ system.

Because this label keeps no separate sections for trial and post-approval reports, everything named above stands in a single section. The full wording is given there.

Sources

1. Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol 2013 · PubMed 24084075
2. Herman JP, McKlveen JM, Ghosal S et al. Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response. Compr Physiol 2016 · PubMed 27065163
3. Priya G, Laway BA, Ayyagari M et al. The Glucocorticoid Taper: A Primer for the Clinicians. Indian J Endocrinol Metab 2024 · PubMed 39371659
4. Chapman K, Holmes M, Seckl J. 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev 2013 · PubMed 23899562
5. Meyer EJ, Nenke MA, Rankin W et al. Corticosteroid-Binding Globulin: A Review of Basic and Clinical Advances. Horm Metab Res 2016 · PubMed 27214312
6. Huybers S, Naber TH, Bindels RJ, Hoenderop JG. Prednisolone-induced Ca2+ malabsorption is caused by diminished expression of the epithelial Ca2+ channel TRPV6. Am J Physiol Gastrointest Liver Physiol 2007 · PubMed 16901990
7. La Corte R, Trotta F, Adami S. Glucocorticoid receptors and bone. Curr Pharm Des 2010 · PubMed 20977422
8. Christakos S, Li S, De La Cruz J et al. Vitamin D and the intestine: Review and update. J Steroid Biochem Mol Biol 2020 · PubMed 31655181
9. Siegel KR, Kassotis CD. Friend and Foe?: Metals as Facilitators and Disruptors of Steroid Nuclear Receptor Signaling. Toxicol Sci 2026 · PubMed 42608812
10. US prescribing information (United States): Prednisolone Oral Solution USP, DailyMed, version of 4 Sept 2026, sections DESCRIPTION and CLINICAL PHARMACOLOGY · Prescribing information
11. US prescribing information (United States): Prednisone Delayed-Release Tablets, DailyMed, version of 12 Aug 2026, sections 12.1 Mechanism of Action and 12.3 Pharmacokinetics (Metabolism) · Prescribing information
12. US prescribing information (United States): Prednisolone Oral Solution USP, DailyMed, version of 4 Sept 2026, section ADVERSE REACTIONS · Prescribing information

Whole pathway: Prednisolon

As of 2026-09-25. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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