Steroid

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This article is about the family of polycyclic chemical compounds. For the performanceenhancing substances, seeAnabolic steroid. For the scientific journal, see Steroids
(journal).

This article may be too technical for most readers to understand. P

helpimprove this article to make it understandable to non-experts, with
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Steroid ring system: The parent ABCD steroid ring system (hydrocarbon framework) is
shown with IUPAC-approved ring lettering and atom numbering.[1]:1785f
A steroid is an organic compound with four rings arranged in a specificconfiguration.
Examples include the dietary lipid cholesterol, the sex
hormonesestradiol and testosterone[2]:1019 and the antiinflammatory drug dexamethasone.[3]Steroids have two principal biological functions:
certain steroids (such as cholesterol) are important components of cell
membranes which alter membrane fluidity, and many steroids are signaling
molecules which activate steroid hormone receptors.
The steroid core structure is composed of seventeen carbon atoms, bonded in four
"fused" rings: three six-member cyclohexane rings (rings A, B and C in the first
illustration) and one five-member cyclopentane ring (the D ring). Steroids vary by the
functional groups attached to this four-ring core and by the oxidation state of the
rings. Sterols are forms of steroids with a hydroxyl group at position three and a
skeleton derived from cholestane.[4][1]:1785f [5] They can also vary more markedly by
changes to the ring structure (for example, ring scissions which
produce secosteroids such as vitamin D3).
Hundreds of steroids are found in plants, animals and fungi. All steroids are
manufactured in cells from the sterols lanosterol(animals and fungi)
or cycloartenol (plants). Lanosterol and cycloartenol are derived from the cyclization of
the triterpenesqualene.[6]

Space-filling representation

Ball-and-stick representation
5-dihydroprogesterone (5-DHP), a steroid. The shape of the four rings of most
steroids is illustrated (carbon atoms in black, oxygens in red and hydrogens in grey).
The apolar "slab" of hydrocarbon in the middle (grey, black) and the polar groups at
opposing ends (red) are common features of natural steroids. 5-DHP is an
endogenous steroid hormone and abiosynthetic intermediate.
Contents
[hide]

1Nomenclature

2Species distribution and function

3Types
o

3.1Intact ring system

3.2Cleaved, contracted, and expanded rings

4Biological significance

5Pharmacological action

6Biosynthesis and metabolism

o

6.1Mevalonate pathway

6.2Steroidogenesis

6.3Alternative pathways

7Catabolism and excretion

8Isolation, structure determination, and methods of analysis

9Chemical synthesis

10Research awards

11See also

12References

13Further reading

14External links
Nomenclature[edit]

A gonane (steroid nucleus)

A gonane, the simplest steroid, is composed of seventeen carbon atoms in carboncarbon bonds forming four fused rings in a three-dimensional shape. The
three cyclohexane rings (A, B, and C in the first illustration) form the skeleton of
a perhydro derivative of phenanthrene. The D ring has acyclopentane structure. When
the two methyl groups and eight carbon side chains (at C-17, as shown for cholesterol)
are present, the steroid is said to have a cholestane framework. The two common 5
and 5 stereoisomeric forms of steroids exist because of differences in the side of the
largely planar ring system where the hydrogen (H) atom at carbon-5 is attached, which
results in a change in steroid A-ring conformation.
Examples of steroid structures are:

Testosterone,
the principal
male sex
hormone and
ananabolic
steroid

Cholic acid, a bile acid,

showing the carboxylic
acid and
additional hydroxyl
groups often present

Progesterone, a steroid
hormone involved in the
female menstrual cycle,
pregnancy, and
embryogenesis

Dexamethasone,
a
syntheticcorticost
eroid drug

Medrogestone, a
synthetic drug with
effects similar to
progesterone

Lanosterol,
the biosynthetic precursor
to animal steroids. The
number of carbons (30)
indicates
itstriterpenoid classificatio
n.

-Sitosterol, a plant or phytosterol,

with a fully branched hydrocarbon
side chain at C-17 and an hydroxyl
group at C-3

In addition to the ring scissions (cleavages), expansions and contractions (cleavage and
reclosing to a larger or smaller rings)all variations in the carbon-carbon bond
frameworksteroids can also vary:

in the bond orders within the rings,

in the number of methyl groups attached to the ring (and, when present, on the
prominent side chain at C17),

in the functional groups attached to the rings and side chain, and

in the configuration of groups attached to the rings and chain. [2]:29

For instance, sterols such as cholesterol and lanosterol have an hydroxyl

group attached at position C-3, while testosteroneand progesterone have a carbonyl
(oxo substituent) at C-3; of these, lanosterol alone has two methyl groups at C-4 and
cholesterol (with a C-5 to C-6 double bond) differs from testosterone and progesterone
(which have a C-4 to C-5 double bond).

Steroid 5 and
5stereoisomers[1]:1786f

Cholesterol,
a prototypical animal sterol.
This structural lipid and key
steroid biosynthetic precursor.
[1]:1785f

5-cholestane, a common
steroid core

Species distribution and function[edit]

The following are some common categories of steroids. In eukaryotes, steroids are
found in fungi, animals, and plants. Fungal steroids include the ergosterols.
Animal steroids include compounds of vertebrate and insect origin, the latter
including ecdysteroids such as ecdysterone(controlling molting in some species).
Vertebrate examples include the steroid hormones and cholesterol; the latter is a
structural component of cell membranes which helps determine the fluidity of cell
membranes and is a principal constituent of plaque (implicated in atherosclerosis).
Steroid hormones include:

Sex hormones, which influence sex differences and support reproduction. These
include androgens, estrogens, andprogestagens.

The corticosteroids, including most synthetic steroid drugs, with natural

product classes the glucocorticoids (which regulate many aspects
of metabolism and immune function) and the mineralocorticoids (which help
maintain blood volume and control renal excretion of electrolytes)

Anabolic steroids, natural and synthetic, which interact with androgen receptors
to increase muscle and bone synthesis. In popular use, the term "steroids" often
refers to anabolic steroids.

Plant steroids include steroidal alkaloids found in Solanaceae,[7] the phytosterols, and
the brassinosteroids (which include several plant hormones). In prokaryotes,
biosynthetic pathways exist for the tetracyclic steroid framework (e.g. inmycobacteria)

[8]

where its origin from eukaryotes is conjectured[9] and the more-common

pentacyclic triterpinoidhopanoid framework.[10]
Types[edit]
Intact ring system[edit]
It is also possible to classify steroids based on their chemical composition. One
example of how MeSH performs this classification is available at the Wikipedia MeSH
catalog. Examples of this classification include:

Cholecalciferol (vitamin D3), an example of a 9,10-secosteroid

Cyclopamine, an example of a complex C-nor-D-homosteroid

Class

Example

Number of carbon atoms

Cholestanes

Cholesterol

27

Cholanes

Cholic acid

24

Pregnanes

Progesterone

21

Androstanes

Testosterone

19

Estranes

Estradiol

18

The gonane (steroid nucleus) is the parent 17-carbon tetracyclic hydrocarbon molecule
with no alkyl sidechains.[11]
Cleaved, contracted, and expanded rings[edit]
Secosteroids (Latin seco, "to cut") are a subclass of steroidal compounds
resulting,biosynthetically or conceptually, from scission (cleavage) of parent steroid
rings (generally one of the four). Major secosteroid subclasses are defined by the
steroid carbon atoms where this scission has taken place. For instance, the prototypical
secosteroid cholecalciferol, vitamin D3 (shown), is in the 9,10-secosteroid subclass and
derives from the cleavage of carbon atoms C-9 and C-10 of the steroid B-ring; 5,6secosteroids and 13,14-steroids are similar.[12]
Norsteroids (nor-, L. norma; "normal" in chemistry, indicating carbon removal) [13] and
homosteroids (homo-, Greek homos; "same", indicating carbon addition) are structural
subclasses of steroids formed from biosynthetic steps. The former involves enzymic ring
expansion-contraction reactions, and the latter is accomplished (biomimetically) or
(more frequently) through ring closures of acyclicprecursors with more (or fewer) ring
atoms than the parent steroid framework.[14]
Combinations of these ring alterations are known in nature. For instance, ewes who
graze on corn lily[disambiguation needed]ingest cyclopamine (shown) and veratramine, two of a
sub-family of steroids where the C- and D-rings are contracted and expanded
respectively via a biosynthetic migration of the original C-13 atom. Ingestion of these Cnor-D-homosteroids results in birth defects in lambs: cyclopia from cyclopamine and leg
deformity from veratramine.[15] A further C-nor-D-homosteroid (nakiterpiosin) is excreted
by Okinawan cyanobacteriosponges Terpios hoshinota leading to coral mortality
from black coral disease.[16] Nakiterpiosin-type steroids are active against the signaling
pathway involving the smoothenedand hedgehog proteins, a pathway which is
hyperactive in a number of cancers.
Biological significance[edit]
Steroids and their metabolites often function as signalling molecules (the most notable
examples are steroid hormones), and steroids and phospholipids are components
of cell membranes. Steroids such as cholesterol decrease membrane fluidity.[17]Similar
to lipids, steroids are highly concentrated energy stores. However, they are not typically
sources of energy; in mammals, they are normally metabolized and excreted.

Pharmacological action[edit]
Two classes of drugs target the mevalonate pathway: statins (used to reduce elevated
cholesterol levels) andbisphosphonates (used to treat a number of bone-degenerative
diseases).
Biosynthesis and metabolism[edit]
The hundreds of steroids found in animals, fungi, and plants are made
from lanosterol (in animals and fungi; see examples above) or cycloartenol (in plants).
Lanosterol and cycloartenol derive from cyclization of the triterpenoid squalene.[6]

Simplification of the end of the steroid synthesis pathway, where the

intermediates isopentenyl pyrophosphate (PP or IPP) anddimethylallyl
pyrophosphate (DMAPP) form geranyl
pyrophosphate (GPP),squalene and lanosterol (the first steroid in the pathway)
Steroid biosynthesis is an anabolic pathway which produces steroids from simple
precursors. A unique biosynthetic pathway is followed in animals (compared to many
other organisms), making the pathway a common target for antibiotics and other antiinfection drugs. Steroid metabolism in humans is also the target of cholesterol-lowering
drugs, such as statins.
In humans and other animals the biosynthesis of steroids follows the mevalonate
pathway, which uses acetyl-CoA as building blocks for dimethylallyl
pyrophosphate(DMAPP) and isopentenyl pyrophosphate (IPP).[18][better source needed] In
subsequent steps DMAPP and IPP join to form geranyl pyrophosphate (GPP), which
synthesizes the steroid lanosterol. Modifications of lanosterol into other steroids are
classified as steroidogenesis transformations.
Mevalonate pathway[edit]
Main article: Mevalonate pathway

Mevalonate pathway
The mevalonate, or HMG-CoA reductase pathway begins with acetyl-CoA and ends
with dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP).
DMAPP and IPP donate isoprene units, which are assembled and modified to
formterpenes and isoprenoids[19] (a large class of lipids, which include
the carotenoidsand form the largest class of plant natural products.[20] Here, the
isoprene units are joined to make squalene and folded into a set of rings to
make lanosterol.[21]Lanosterol can then be converted into other steroids, such as
cholesterol andergosterol.[21][22]
Steroidogenesis[edit]

Human steroidogenesis, with the major classes of steroid hormones, individual steroids
and enzymaticpathways. Changes in molecular structure from a precursor are
highlighted in white.
Steroidogenesis is the biological process by which steroids are generated from
cholesterol and changed into other steroids. [23] The pathways of steroidogenesis differ

among species. The major classes of steroid hormones, with prominent members and
examples of related functions, are:

Progestogens:

Progesterone, which regulates cyclical changes in the endometrium of

theuterus and maintains a pregnancy
Corticosteroids (corticoids):

Aldosterone, a mineralocorticoid which helps regulate blood pressure

Cortisol, a glucocorticoid whose functions include immunosuppression

Androgens:

Testosterone, which contributes to the development and maintenance of

male secondary sex characteristics
Estrogens:

Estrogen, which contributes to the development and maintenance of

female secondary sex characteristics

Human steroidogenesis occurs in a number of locations:

Progestogens are the precursors of all other human steroids, and all human
tissues which produce steroids must first convert cholesterol to pregnenolone. This
conversion is the rate-limiting step of steroid synthesis, which occurs inside
the mitochondrion of the respective tissue.[24]
Corticosteroids are produced in the adrenal cortex.

Estrogen and progesterone are made primarily in the ovary and

the placentaduring pregnancy, and testosterone in the testes.

Testosterone is also converted to estrogen to regulate the supply of each in

females and males.

Some neurons and glia in the central nervous system (CNS) express
the enzymes required for the local synthesis ofpregnane neurosteroids, de novo or
from peripheral sources.
Alternative pathways[edit]

In plants and bacteria, the non-mevalonate pathway uses pyruvate and glyceraldehyde
3-phosphate as substrates.[19][25]
Catabolism and excretion[edit]
Steroids are primarily oxidized by cytochrome P450 oxidase enzymes, such
as CYP3A4. These reactions introduce oxygen into the steroid ring, allowing the
cholesterol to be broken up by other enzymes into bile acids. [26] These acids can then be
eliminated by secretion from the liver in bile.[27] The expression of the oxidase gene can
be upregulated by the steroid sensor PXR when there is a high blood concentration of
steroids.[28] Steroid hormones, lacking the side chain of cholesterol and bile acids, are
typically hydroxylated at various ring positions or oxidized at the 17
position, conjugted with sulfate orglucuronic acid and excreted in the urine.[29]
Isolation, structure determination, and methods of analysis[edit]
Steroid isolation, depending on context, is the isolation of chemical matter required
for chemical structure elucidation, derivitzation or degradation chemistry, biological
testing, and other research needs (generally milligrams to grams, but often more [30] or
the isolation of "analytical quantities" of the substance of interest (where the focus is on
identifying and quantifying the substance (for example, in biological tissue or fluid). The
amount isolated depends on the analytical method, but is generally less than one
microgram.[31][page needed] The methods of isolation to achieve the two scales of product are
distinct, but include extraction, precipitation, adsorption, chromatography,
and crystallization. In both cases, the isolated substance is purified to chemical
homogeneity; combined separation and analytical methods, such as LC-MS, are chosen
to be "orthogonal"achieving their separations based on distinct modes of interaction
between substance and isolating matrixto detect a single species in the pure
sample. Structure determination refers to the methods to determine the chemical
structure of an isolated pure steroid, using an evolving array of chemical and physical
methods which have included NMRand small-molecule crystallography.[2]:1019 Methods
of analysis overlap both of the above areas, emphasizing analytical methods to
determining if a steroid is present in a mixture and determining its quantity.[31]
Chemical synthesis[edit]
Microbial catabolism of phytosterol sidechains yields C-19 steroids, a precursor to most
steroid hormones, or C-22 steroids (a precursor to adrenocortical hormones).[32][33]
The chemical conversion of sapogenins to steroidse.g., via the Marker degradation
is a method of partial synthesis that is a long-established alternative to microbial
transformation of phytosterols to steroids, and underpinned Syntex efforts using
the Mexican barbasco trade (harvesting and marketing large tubers of wild-growing
plants, e.g., yams) to produce early synthetic steroids. [30]
Research awards[edit]
A number of Nobel Prizes have been awarded for steroid research, including:

1927 (Chemistry) Heinrich Otto Wieland Constitution of bile acids and sterols
and their connection to vitamins[34]

1928 (Chemistry) Adolf Otto Reinhold Windaus Constitution of sterols and their
connection to vitamins[35]

1939 (Chemistry) Adolf Butenandt and Leopold Ruzicka Isolation and structural
studies of steroid sex hormones, and related studies on higher terpenes[36]

1950 (Physiology or Medicine) Edward Calvin Kendall, Tadeus Reichstein,

and Philip Hench Structure and biological effects of adrenal hormones[37]

1965 (Chemistry) Robert Burns Woodward In part, for the synthesis of

cholesterol, cortisone, and lanosterol[38]

1969 (Chemistry) Derek Barton and Odd Hassel Development of the concept of
conformation in chemistry, emphasizing the steroid nucleus [39]

1975 (Chemistry) Vladimir Prelog In part, for developing methods to determine

the stereochemical course of cholesterol biosynthesis from mevalonic
acid via squalene[40]

See also[edit]
pharmacology portal

Batrachotoxin

List of steroid abbreviations

Pheromone

Reverse cholesterol transport

Steroid hydroxylases

Steroid sulfatase

Steroidogenic acute regulatory protein

Membrane steroid receptor

References[edit]

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