SHBG (Sexualhormon-bindendes Globulin): the pathway in the body

SHBG (Sexualhormon-bindendes Globulin) is part of the pathway “Testosterone”. This page shows the whole pathway; the station of SHBG (Sexualhormon-bindendes Globulin) is highlighted.

Where this laboratory value sits: Testosterone in blood — bound to SHBG and albumin. In the blood, most of it is bound to SHBG and to albumin. Only the free and the loosely bound fractions reach the cells. SHBG also slows breakdown. Source 3

In brief

Testosterone is the main androgen, a steroid hormone made from cholesterol. The Leydig cells of the testis form it; in the cell it binds the androgen receptor, which co-determines which genes are read. How much acts depends on SHBG and on conversion to DHT and estradiol.

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 transport The protein StAR channels cholesterol into the mitochondrion. There, the enzyme CYP11A1 cleaves off part of the side chain, forming pregnenolone, the shared precursor of all steroid hormones. The amount of all following hormones depends on this step. Source 1↑ supplies The step via StAR and CYP11A1 is the slowest of the whole pathway and determines how much steroid hormone is made overall. Pregnenolone feeds all following steps. established physiology Source 1
   ⚖ When the balance tips

   too much — If more pregnenolone forms, the following enzymes have more starting material; production rises until these enzymes are working at capacity.

   too little — If little cholesterol passes through StAR into the mitochondrion, little pregnenolone forms, and all following steroid hormones of the cell become scarce.

   established physiology · Source 1

2. Pregnenolone → DHEA CYP17A1 CYP17A1 works in two steps: first it attaches an OH group, then it splits off two carbon atoms. This forms DHEA. DHEA itself is only weakly androgenic. Source 1↑ supplies DHEA itself is only a weak androgen; it feeds the path to androstenedione and testosterone. For the cleavage, CYP17A1 needs P450 oxidoreductase, assisted by cytochrome b5. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot of DHEA is present, part of it is turned into DHEA sulfate by attaching sulfate, a water-soluble form that stays in the blood for a long time; the rest moves on via 3-beta-HSD.

   too little — If CYP17A1 cleaves little, little DHEA forms, and the precursor for androstenedione and testosterone becomes scarce.

   established physiology · Source 1

3. DHEA → Androstenedione 3-beta-HSD · NAD+ The enzyme 3-beta-HSD converts the OH group into a keto group and shifts a double bond in the ring system. It is the direct precursor of testosterone. Source 1↑ supplies Androstenedione is the direct precursor of testosterone. Aromatase can also convert it into estrone; it thus stands at the fork between androgens and estrogens. established physiology Source 1
   ⚖ When the balance tips

   too much — If androstenedione builds up, more of it is converted by aromatase into estrone, above all in adipose tissue.

   too little — If little androstenedione is available, 17-beta-HSD3 has little starting material, and less testosterone is made.

   established physiology · Source 1

4. Androstenedione → Testosterone 17-beta-HSD3 · NADPH 17-beta-HSD3 turns the keto group at position 17 into an OH group. Testosterone is then complete and passes from the cell into the blood. Part of it stays in the testis for sperm production. Source 1, 2↑ supplies In the testis, testosterone acts in high amounts directly on sperm production. Released into the blood, it reaches muscle, bone and other tissues and at the same time slows LH release from the pituitary. established physiology Source 2, 1
   ⚖ When the balance tips

   too much — If testosterone in the blood rises, it slows the release of LH and FSH via the hypothalamus and pituitary; the Leydig cells then receive less stimulus, and production in the testis falls.

   too little — If the Leydig cell makes little testosterone, the brake on the hypothalamus and pituitary is weaker, and more LH is released.

   established physiology · Source 2, 1

5. Testosterone in blood → Breakdown in the liver Liver enzymes The liver converts testosterone into androsterone and etiocholanolone and couples these to glucuronic acid. In this water-soluble form, it leaves the body via the urine. The breakdown products barely act. Source 1↓ depletes Breakdown in the liver removes testosterone from the blood for good: androsterone and etiocholanolone barely act at the receptor, and coupling to glucuronic acid makes them excretable. established physiology Source 1
   ⚖ When the balance tips

   too much — If breakdown runs faster, testosterone leaves the blood more quickly, and the testis has to make more to keep the amount the same.

   too little — If breakdown runs more slowly, testosterone stays in the blood longer, and the feedback on LH is stronger.

   established physiology · Source 1

6. Testosterone in blood → Free testosterone · Release from SHBG SHBG holds on to testosterone and releases it only slowly. It thus acts as a buffer between production in the testis and uptake into the cell. Mainly this fraction enters the cells. Source 3↑ supplies Mainly the free fraction passes through the cell membrane and reaches the androgen receptor, 5-alpha reductase and aromatase. It is the amount that can act directly in the tissues. established physiology Source 3
   ⚖ When the balance tips

   too much — If a lot of testosterone is free, more enters the cells; there more is converted into DHT and estradiol, and it is also broken down faster.

   too little — If little testosterone is free, less of it reaches the cells, even if a lot is bound in the blood overall.

   established physiology · Source 3

7. Free testosterone → DHT 5-alpha reductase · NADPH 5-alpha reductase converts testosterone into dihydrotestosterone. DHT binds more tightly to the androgen receptor and keeps the signal going there for longer. It acts mainly in skin, hair follicles and prostate. Source 1↑ supplies DHT amplifies the androgen signal where 5-alpha reductase is located, for example in the prostate, skin and hair follicles. Aromatase cannot convert DHT into estradiol. established physiology Source 1, 4
   ⚖ When the balance tips

   too much — If 5-alpha reductase makes a lot of DHT, a stronger androgen signal arrives in the skin, hair follicles and prostate; in the scalp hair follicles it shortens the growth phase.

   too little — If little 5-alpha reductase is active, more testosterone stays unchanged, and a weaker androgen signal arrives in these tissues.

   established physiology · Source 4, 1

8. Free testosterone → Estradiol Aromatase (CYP19A1) Aromatase converts a small part of testosterone into estradiol. It is found in adipose tissue, in the brain and in the testis itself, among other places. Estradiol also acts on bone in men. Source 1↕ both, depending on amount The conversion draws off testosterone and at the same time supplies estradiol, which acts via the estrogen receptor. In men, too, estradiol contributes to the maturation and maintenance of bone. established physiology Source 1
   ⚖ When the balance tips

   too much — If aromatase converts a lot of testosterone, for example in abundant adipose tissue, more estradiol forms, and part of the testosterone is lost to the androgen signal.

   too little — If little testosterone is converted into estradiol, bone is missing a signal that closes the growth plates and maintains bone mass.

   established physiology · Source 1

9. Free testosterone → Androgen receptor Inside the cell, testosterone and DHT bind to the same receptor. The loaded receptor then moves into the cell nucleus. Without hormone it stays in the cytoplasm. Source 1↑ supplies The loaded receptor becomes a switch for genes: in muscle for building muscle protein, in bone for maintaining bone mass, in the male reproductive organs for their development. established physiology Source 6
   ⚖ When the balance tips

   too much — If a lot of testosterone and DHT bind, more loaded receptors move into the nucleus, and their target genes are read more often.

   too little — If little hormone is present, the receptor stays largely unloaded in the cytoplasm, and its target genes are read less often.

   established physiology · Source 6

10. Androgen receptor → Reading genes In the nucleus, the receptor attaches to specific sections of DNA and there regulates which proteins the cell makes. In this way it acts on muscle protein, bone and blood formation. Source 1↑ supplies Through the genes that are read, muscle builds more protein, bone maintains its mass, and the bone marrow makes more red blood cells. established physiology Source 6
    ⚖ When the balance tips

    too much — If the target genes are read strongly, muscle builds more protein and the bone marrow makes more red blood cells; their share in the blood rises.

    too little — If they are read little, protein breakdown predominates in muscle, bone is rebuilt more slowly, and fewer red blood cells form.

    established physiology · Source 6

Further stations

• Cholesterol — starting material All steroid hormones derive from cholesterol. In the Leydig cells of the testis, it is kept ready, stored in small droplets. LH sets the pace of processing. Source 1, 2↑ supplies Cholesterol provides the ring skeleton from which the Leydig cell builds testosterone. It comes from the stored droplets, from lipoproteins in the blood and from the cell's own synthesis. established physiology Source 1, 2
  ⚖ When the balance tips

  too much — If more cholesterol is available than StAR can move into the mitochondrion, it stays stored in the droplets; the pace is set by transport, not by the store.

  too little — If little cholesterol is in the cell, it draws more on lipoproteins from the blood and on its own synthesis to feed the pathway.

  established physiology · Source 1, 2

• LH from the pituitary — controls the first step The hormone LH from the pituitary gland binds to the Leydig cell. It mainly controls how much cholesterol enters the mitochondrion, which is the slowest step of the pathway. Testosterone in turn slows LH release. Source 2↑ supplies LH binds to its receptor on the Leydig cell and, via cAMP, raises the amount and activity of StAR; more cholesterol thus enters the mitochondrion. Over time, LH also keeps the enzymes of the pathway ready. established physiology Source 2
  ⚖ When the balance tips

  too much — If a lot of LH arrives, the Leydig cell makes more testosterone until its feedback slows LH release again.

  too little — If little LH arrives, less cholesterol enters the mitochondrion, and the Leydig cell makes less testosterone.

  established physiology · Source 2

• Testosterone in blood — bound to SHBG and albumin In the blood, most of it is bound to SHBG and to albumin. Only the free and the loosely bound fractions reach the cells. SHBG also slows breakdown. Source 3↕ both, depending on amount Binding to SHBG holds testosterone back in the blood and slows its breakdown; binding to albumin is loose and releases it easily in the tissues. The balance of both determines how much can act. established physiology Source 3
  ⚖ When the balance tips

  too much — If there is a lot of SHBG in the blood, more testosterone is tightly bound; the free fraction falls even if the total amount stays the same.

  too little — If there is little SHBG in the blood, more testosterone is free or loosely bound; it reaches the cells more easily and is also broken down faster.

  established physiology · Source 3

Cofactors in this pathway

• NADPH — Electron donor for CYP11A1, CYP17A1, 17-beta-HSD3 and 5-alpha-reductase; without NADPH the route stalls Source 1
• Iron — Central atom of the haem in the cytochrome P450 enzymes of this route; there it binds the oxygen Source 1In the ORY catalogue as a laboratory value: Eisen
• NAD⁺ — Accepts hydrogen at 3-beta-HSD and so turns DHEA into androstenedione Source 1In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Zinc — Keeps the two zinc fingers in the DNA-binding part of the androgen receptor in shape so that it binds to DNA Source 6In the ORY catalogue as a laboratory value: Zink

What acts on this pathway

• Finasteride — Finasteride inhibits type II 5-alpha reductase. As a result, less testosterone is converted to DHT; this mechanism is described in pharmacology. Source 4
• Anastrozole — Anastrozole blocks aromatase. The conversion of testosterone to estradiol decreases as a result; this mechanism is also described in pharmacology. Source 5

Sources

1. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011 · PubMed 21051590
2. Zirkin BR, Papadopoulos V. Leydig cells: formation, function, and regulation. Biol Reprod 2018 · PubMed 29566165
3. Hammond GL. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol 2016 · PubMed 27113851
4. Yim E, Nole KL, Tosti A. 5alpha-Reductase inhibitors in androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes 2014 · PubMed 25268732
5. Kelly CM, Buzdar AU. Anastrozole. Expert Opin Drug Saf 2010 · PubMed 20923259
6. Davey RA, Grossmann M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin Biochem Rev 2016 · PubMed 27057074

Whole pathway: Testosterone

Related pathways

• Estradiol — cholesterol
• DHEA — 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 approval pending
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