Steroid

IUPAC recommended ring lettering (left) and atom numbering (right) of the steroid skeleton.[1][2] The four rings A-D form a sterane core.

Stick model of the steroid lanosterol. The total number of carbons (30) reflects its triterpenoid origin.

A steroid is a type of organic compound that contains a specific arrangement of four rings that are joined to each other. Examples of steroids include cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.

The sterane core of steroids is composed of seventeen carbon atoms bonded together to form four fused rings: three cyclohexane rings (designated as rings A, B, and C in the figure to the right) and one cyclopentane ring (the D ring). The steroids vary by the functional groups attached to these rings and by the oxidation state of the rings. Sterols are special forms of steroids, with a hydroxyl group at position-3 and a skeleton derived from cholestane.^[2]

Hundreds of distinct steroids are found in plants, animals, and fungi. All steroids are made in cells either from the sterols lanosterol (animals and fungi) or cycloartenol (plants). Both, lanosterol and cycloartenol, are derived from the cyclization of the triterpene squalene.^[3]

Classification

Taxonomical/Functional

Some of the common categories of steroids:

• Animal steroids
  • Insect steroids
    • Ecdysteroids such as ecdysterone
  • Vertebrate steroids
    • Steroid hormones
      • Sex steroids are a subset of sex hormones that produce sex differences or support reproduction. They include androgens, estrogens, and progestagens.
      • Corticosteroids include glucocorticoids and mineralocorticoids. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Most medical 'steroid' drugs are corticosteroids.
      • Anabolic steroids are a class of steroids that interact with androgen receptors to increase muscle and bone synthesis. There are natural and synthetic anabolic steroids. In popular language, the word "steroids" usually refers to anabolic steroids.
    • Cholesterol, which modulates the fluidity of cell membranes and is the principal constituent of the plaques implicated in atherosclerosis.
• Plant steroids
  • Phytosterols
  • Brassinosteroids
• Fungus steroids
  • Ergosterols

Structural

It is also possible to classify steroids based upon their chemical composition. One example of how MeSH performs this classification is available at the Wikipedia MeSH catalog. Examples from this classification include:

Gonane (or steroid nucleus) is the hypothetic parent (17-carbon tetracyclic) hydrocarbon molecule without any alkyl sidechains.^[4]

Metabolism

Steroids include estrogen, cortisol, progesterone, and testosterone. Estrogen and progesterone are made primarily in the ovary and in the placenta during pregnancy, and testosterone in the testes. Testosterone is also converted into estrogen to regulate the supply of each, in the bodies of both females and males. Certain neurons and glia in the central nervous system (CNS) express the enzymes that are required for the local synthesis of pregnane neurosteroids, either de novo or from peripherally-derived sources. The rate-limiting step of steroid synthesis is the conversion of cholesterol to pregnenolone, which occurs inside the mitochondrion.^[5]

Simplified version of latter part of steroid synthesis pathway, where the intermediates isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) form geranyl pyrophosphate (GPP), squalene and, finally, lanosterol, the first steroid in the pathways. Some intermediates are omitted for clarity.

Steroid metabolism is the complete set of chemical reactions in organisms that produce, modify and consume steroids. These metabolic pathways include:

• steroid synthesis – the manufacture of steroids from simpler precursors
• steroidogenesis – the interconversion of different types of steroids
• steroid degradation.

Steroid biosynthesis

Steroid biosynthesis is an anabolic metabolic pathway that produces steroids from simple precursors. This pathway is carried out in different ways in animals than in many other organisms, making the pathway a common target for antibiotics and other anti-infective drugs. In addition, steroid metabolism in humans is the target of cholesterol-lowering drugs such as statins.

It starts in the mevalonate pathway in humans, with Acetyl-CoA as building blocks, which form DMAPP and IPP^[6]. In following steps, DMAPP and IPP form lanosterol, the first steroid. Further modification belongs to the succeeding steroidogenesis.

Mevalonate pathway

Mevalonate pathway

The mevalonate pathway or HMG-CoA reductase pathway starts with and ends with dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP).

Regulation and feedback

Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (Sterol Regulatory Element-Binding Protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.

Pharmacology

A number of drugs target the mevalonate pathway:

• Statins (used for elevated cholesterol levels)
• Bisphosphonates (used in treatment of various bone-degenerative diseases)

Plants and bacteria

In plants and bacteria, the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates.^[7][8]

DMAPP to lanosterol

Isopentenyl pyrophosphate and dimethylallyl pyrophosphate donate isoprene units, which are assembled and modified to form terpenes and isoprenoids^[8], which are a large class of lipids that include the carotenoids, and form the largest class of plant natural products.^[9]

Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol.^[10] Lanosterol can then be converted into other steroids such as cholesterol and ergosterol.^[10][11]

Human Steroidogenesis

Steroidogenesis

Steroidogenesis is the biological process by which steroids are generated from cholesterol and transformed into other steroids. The pathways of steroidogenesis differ between different species, but the pathways of human steroidogenesis are shown in the figure.

Products of steroidogenesis include:

• androgens
  • testosterone
• estrogens and progesterone
• corticoids
  • cortisol
  • aldosterone

Elimination

Steroids are mainly oxidized by cytochrome P450 oxidase enzymes, such as CYP3A4. These reactions introduce oxygen into the steroid ring and allows the structure to be broken up by other enzymes, to form bile acids as final products.^[12] These bile acids can then be eliminated through secretion from the liver in the bile.^[13] The expression of this oxidase gene can be upregulated by the steroid sensor PXR when there is a high blood concentration of steroids.^[14]

See also

• Batrachotoxin
• List of steroid abbreviations

References

Further reading

External links

• Nomenclature of Steroids Home Page at Queen Mary University of London.
• Steroidogenesis