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Steroid

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This article is about the family of polycyclic compounds. For the drugs, also used as performance-enhancing substances, seeAnabolic steroid.For the scientific journal, seeSteroids (journal).For the Death Grips EP, seeSteroids (Crouching Tiger Hidden Gabber Megamix).

Complex chemical diagram
Structure of 24-ethyl-lanostane,a prototypical steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is shown withIUPAC-approved ring lettering and atom numbering.[1]: 1785f 

Asteroidis anorganic compoundwith fourfusedrings (designated A, B, C, and D) arranged in a specificmolecular configuration.

Steroids have two principal biological functions: as important components ofcell membranesthat altermembrane fluidity;and assignaling molecules.Examples include thelipidcholesterol,sex hormonesestradiolandtestosterone,[2]: 10–19 anabolic steroids,and theanti-inflammatorycorticosteroid drugdexamethasone.[3]Hundreds of steroids are found infungi,plants,andanimals.All steroids are manufactured in cells from thesterolslanosterol(opisthokonts) orcycloartenol(plants). Lanosterol and cycloartenol are derived from thecyclizationof thetriterpenesqualene.[4]

Steroids are named after the steroidcholesterol[5]which was first described in gall stones fromAncient Greekchole-'bile' andstereos'solid'.[6][7][8]

The steroid nucleus (core structure) is calledgonane(cyclopentanoperhydrophenanthrene).[9]It is typically composed of seventeencarbonatoms, bonded in four fused rings: three six-membercyclohexanerings (rings A, B and C in the first illustration) and one five-membercyclopentanering (the D ring). Steroids vary by thefunctional groupsattached to this four-ring core and by theoxidation stateof the rings.Sterolsare forms of steroids with ahydroxy groupat position three and a skeleton derived fromcholestane.[1]: 1785f [10]Steroids can also be more radically modified, such as by changes to the ring structure, for example,cuttingone of the rings. Cutting Ring B producessecosteroidsone of which isvitamin D3.

Filled-in diagram of a steroid
Space-filling representation
Ball-and-stick diagram of the same steroid
Ball-and-stick representation
5α-dihydroprogesterone (5α-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). Thenonpolar"slab" ofhydrocarbonin the middle (grey, black) and thepolargroups at opposing ends (red) are common features of natural steroids.5α-DHPis an endogenoussteroid hormoneand abiosyntheticintermediate.

Nomenclature

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Rings and functional groups

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See also:GonaneandSterane
Chemical diagram
Gonane,the simplest steroid, consisting only of the common steroid nucleus
Chemical diagram
Steroid 5α and 5βstereoisomers[1]: 1786f 

Gonane,also known as steran or cyclopentanoperhydrophenanthrene, the simplest steroid and the nucleus of all steroids and sterols,[11][12]is composed of seventeencarbonatoms in carbon-carbon bonds forming fourfused ringsin athree-dimensional shape.The threecyclohexanerings (A, B, and C in the first illustration) form the skeleton of aperhydroderivative ofphenanthrene.The D ring has acyclopentanestructure. When the two methyl groups and eight carbonside chains(at C-17, as shown for cholesterol) are present, the steroid is said to have a cholestane framework. The two common 5α and 5β 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. Isomerisation at the C-21 side chain produces a parallel series of compounds, referred to as isosteroids.[13]

Examples of steroid structures are:

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

  • in thebond orderswithin 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 theconfigurationof groups attached to the rings and chain.[2]: 2–9 

For instance,sterolssuch as cholesterol and lanosterol have ahydroxyl groupattached at position C-3, whiletestosteroneandprogesteronehave a carbonyl (oxo substituent) at C-3. Among these compounds, onlylanosterolhas two methyl groups at C-4. Cholesterol which has a C-5 to C-6 double bond, differs from testosterone and progesterone which have a C-4 to C-5 double bond.

Chemical diagram
Cholesterol,aprototypicalanimal sterol. This structurallipidand key steroidbiosyntheticprecursor.[1]: 1785f 
Chemical diagram
5α-cholestane,a common steroid core

Naming convention

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Almost all biologically relevant steroids can be presented as a derivative of a parentcholesterol-likehydrocarbonstructure that serves as askeleton.[14][15]These parent structures have specific names, such aspregnane,androstane,etc. The derivatives carry variousfunctional groupscalled suffixes or prefixes after the respective numbers, indicating their position in the steroid nucleus.[16]There are widely used trivial steroid names of natural origin with significant biologic activity, such asprogesterone,testosteroneorcortisol.Some of these names are defined in The Nomenclature of Steroids.[17]These trivial names can also be used as a base to derive new names, however, by adding prefixes only rather than suffixes, e.g., the steroid17α-hydroxyprogesteronehas ahydroxy group(-OH) at position 17 of the steroid nucleus comparing to progesterone.

The letters α and β[18]denote absolutestereochemistryatchiral centers—a specific nomenclature distinct from theR/S convention[19]of organic chemistry to denote absolute configuration of functional groups, known asCahn–Ingold–Prelog priority rules.The R/S convention assigns priorities to substituents on a chiral center based on their atomic number. The highest priority group is assigned to the atom with the highest atomic number, and the lowest priority group is assigned to the atom with the lowest atomic number. The molecule is then oriented so that the lowest priority group points away from the viewer, and the remaining three groups are arranged in order of decreasing priority around the chiral center. If this arrangement is clockwise, it is assigned an R configuration; if it is counterclockwise, it is assigned an S configuration.[20]In contrast, steroid nomenclature uses α and β to denote stereochemistry at chiral centers. The α and β designations are based on the orientation of substituents relative to each other in a specific ring system. In general, α refers to a substituent that is oriented towards the plane of the ring system, while β refers to a substituent that is oriented away from the plane of the ring system. In steroids drawn from the standard perspective used in this paper, α-bonds are depicted on figures as dashed wedges and β-bonds as solid wedges.[14]

The name "11-deoxycortisol"is an example of a derived name that uses cortisol as a parent structure without anoxygenatom(hence "deoxy" ) attached to position 11 (as a part of a hydroxy group).[14][21]The numbering of positions ofcarbonatoms in the steroid nucleus is set in a template found in the Nomenclature of Steroids[22]that is used regardless of whether an atom is present in the steroid in question.[14]

Unsaturatedcarbons (generally, ones that are part of a double bond) in the steroid nucleus are indicated by changing -ane to -ene.[23]This change was traditionally done in the parent name, adding a prefix to denote the position, with or without Δ (Greek capital delta) which designates unsaturation, for example, 4-pregnene-11β,17α-diol-3,20-dione (also Δ4-pregnene-11β,17α-diol-3,20-dione) or4-androstene-3,11,17-trione(also Δ4-androstene-3,11,17-trione). However, the Nomenclature of Steroids recommends thelocantof a double bond to be always adjacent to the syllable designating the unsaturation, therefore, having it as a suffix rather than a prefix, and without the use of the Δ character, i.e. pregn-4-ene-11β,17α-diol-3,20-dione orandrost-4-ene-3,11,17-trione.The double bond is designated by the lower-numbered carbon atom, i.e. "Δ4- "or" 4-ene "means the double bond between positions 4 and 5. The saturation of carbons of a parent steroid can be done by adding" dihydro- "prefix,[24]i.e., a saturation of carbons 4 and 5 of testosterone with twohydrogenatoms is 4,5α-dihydrotestosterone or 4,5β-dihydrotestosterone. Generally, when there is no ambiguity, one number of a hydrogen position from a steroid with a saturated bond may be omitted, leaving only the position of the second hydrogen atom, e.g.,5α-dihydrotestosteroneor5β-dihydrotestosterone.The Δ5-steroids are those with a double bond between carbons 5 and 6 and the Δ4steroids are those with a double bond between carbons 4 and 5.[25][23]

The abbreviations like "P4"forprogesteroneand "A4"forandrostenedionefor refer to Δ4-steroids, while "P5"forpregnenoloneand "A5"forandrostenediolrefer to Δ5-steroids.[14]

The suffix -ol denotes ahydroxy group,while the suffix -one denotes an oxo group. When two or three identical groups are attached to the base structure at different positions, the suffix is indicated as -diol or -triol for hydroxy, and -dione or -trione for oxo groups, respectively. For example,5α-pregnane-3α,17α-diol-20-onehas a hydrogen atom at the 5α position (hence the "5α-" prefix), two hydroxy groups (-OH) at the 3α and 17α positions (hence "3α,17α-diol" suffix) and an oxo group (=O) at the position 20 (hence the "20-one" suffix). However, erroneous use of suffixes can be found, e.g., "5α-pregnan-17α-diol-3,11,20-trione"[26][sic] — since it has just one hydroxy group (at 17α) rather than two, then the suffix should be -ol, rather than -diol, so that the correct name to be "5α-pregnan-17α-ol-3,11,20-trione".

According to the rule set in the Nomenclature of Steroids, the terminal "e" in the parent structure name should be elided before thevowel(the presence or absence of a number does not affect such elision).[14][16]This means, for instance, that if the suffix immediately appended to the parent structure name begins with a vowel, the trailing "e" is removed from that name. An example of such removal is "5α-pregnan-17α-ol-3,20-dione",where the last" e "of"pregnane"is dropped due to the vowel (" o ") at the beginning of the suffix -ol. Some authors incorrectly use this rule, eliding the terminal" e "where it should be kept, or vice versa.[27]

The term "11-oxygenated" refers to the presence of an oxygen atom as an oxo (=O) or hydroxy (-OH) substituent at carbon 11. "Oxygenated" is consistently used within the chemistry of the steroids[28]since the 1950s.[29]Some studies use the term "11-oxyandrogens"[30][31]as an abbreviation for 11-oxygenated androgens, to emphasize that they all have an oxygen atom attached to carbon at position 11.[32][33]However, in chemical nomenclature, the prefix "oxy" is associated with ether functional groups, i.e., acompoundwith an oxygen atom connected to twoalkylorarylgroups (R-O-R),[34]therefore, using "oxy" within the name of a steroid class may be misleading. One can find clear examples of "oxygenated" to refer to a broad class of organic molecules containing a variety of oxygen containing functional groups in other domains of organic chemistry,[35]and it is appropriate to use this convention.[14]

Even though "keto" is a standard prefix in organic chemistry, the 1989 recommendations of the Joint Commission on Biochemical Nomenclature discourage the application of the prefix "keto" for steroid names, and favor the prefix "oxo" (e.g., 11-oxo steroids rather than 11-keto steroids), because "keto" includes the carbon that is part of the steroid nucleus and the same carbon atom should not be specified twice.[36][14]

Species distribution

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Steroids are found in all domains of life includingbacteria,archaea,andeukaryotes.In eukaryotes, steroids are found in fungi, plants, and animals.[37][38]

Eukaryotic and Prokaryotic

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Eukaryoticcells, which include animals, plants, fungi, and protists, have complex cellular structures with a true nucleus and membrane-bound organelles.[39]

Steroids are integral to eukaryotic cellular membranes, where they help maintain membrane integrity and function.[40]

Duringeukaryogenesis(the emergence of modern eukaryotic cells), steroids likely played a role in the acquisition of mitochondria via endocytosis.[41]

Inprokaryotes,biosynthetic pathways exist for the tetracyclic steroid framework (e.g. inmyxobacteria)[42]– where its origin fromeukaryotesis conjectured[43]– and the more-common pentacyclictriterpinoidhopanoidframework.[44]

Fungal

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Fungal steroids include theergosterols,which are involved in maintaining the integrity of the fungal cellular membrane. Variousantifungal drugs,such asamphotericin Bandazole antifungals,utilize this information to killpathogenicfungi.[45]Fungi can alter their ergosterol content (e.g. through loss of function mutations in the enzymesERG3orERG6,inducing depletion of ergosterol, or mutations that decrease the ergosterol content) to develop resistance to drugs that target ergosterol.[46]

Ergosterol is analogous to thecholesterolfound in the cellular membranes of animals (including humans), or thephytosterolsfound in the cellular membranes of plants.[46]All mushrooms contain large quantities of ergosterol, in the range of tens to hundreds of milligrams per 100 grams of dry weight.[46]Oxygen is necessary for the synthesis ofergosterolin fungi.[46]

Ergosterol is responsible for thevitamin Dcontent found in mushrooms; ergosterol is chemically converted into provitamin D2 by exposure toultraviolet light.[46]Provitamin D2 spontaneously forms vitamin D2.[46]However, not all fungi utilize ergosterol in their cellular membranes; for example, the pathogenic fungal speciesPneumocystis jiroveciidoes not, which has important clinical implications (given the mechanism of action of many antifungal drugs). Using the fungusSaccharomyces cerevisiaeas an example, other major steroids includeergosta‐5,7,22,24(28)‐tetraen‐3β‐ol,zymosterol,andlanosterol.S. cerevisiaeutilizes5,6‐dihydroergosterolin place of ergosterol in its cell membrane.[46]

Plant

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Plant steroids include steroidalalkaloidsfound inSolanaceae[47]andMelanthiaceae(specially the genusVeratrum),[48]cardiac glycosides,[49]thephytosterolsand thebrassinosteroids(which include several plant hormones).

Animal

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Animal steroids include compounds ofvertebrateandinsectorigin, the latter includingecdysteroidssuch asecdysterone(controlling molting in some species). Vertebrate examples include thesteroid hormonesand cholesterol; the latter is a structural component ofcell membranesthat helps determine the fluidity ofcell membranesand is a principal constituent ofplaque(implicated inatherosclerosis). Steroid hormones include:

Types

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By function

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The major classes ofsteroid hormones,with prominent members and examples of related functions, are:[50][51]

Additional classes of steroids include:

As well as the following class ofsecosteroids(open-ring steroids):

By structure

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Intact ring system

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Steroids can be classified based on their chemical composition.[52]One example of howMeSHperforms this classification is available at the Wikipedia MeSH catalog. Examples of this classification include:

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

In biology, it is common to name the above steroid classes by the number of carbon atoms present when referring to hormones: C18-steroids for the estranes (mostly estrogens), C19-steroids for the androstanes (mostly androgens), and C21-steroids for the pregnanes (mostly corticosteroids).[53]The classification "17-ketosteroid"is also important in medicine.

The gonane (steroid nucleus) is the parent 17-carbon tetracyclic hydrocarbon molecule with noalkylsidechains.[54]

Cleaved, contracted, and expanded rings

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Secosteroids (Latinseco,"to cut" ) are a subclass of steroidal compounds resulting,biosyntheticallyor 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 secosteroidcholecalciferol,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; 5,6-secosteroids and 13,14-steroids are similar.[55]

Norsteroids(nor-,L.norma;"normal" in chemistry, indicating carbon removal)[56]and homosteroids (homo-, Greekhomos;"same", indicating carbon addition) are structural subclasses of steroids formed from biosynthetic steps. The former involves enzymicring expansion-contractionreactions, and the latter is accomplished (biomimetically) or (more frequently) throughring closuresofacyclicprecursors with more (or fewer) ring atoms than the parent steroid framework.[57]

Combinations of these ring alterations are known in nature. For instance,eweswho graze oncorn lilyingestcyclopamine(shown) andveratramine,two of a sub-family of steroids where the C- and D-rings are contracted and expanded respectively via abiosyntheticmigration of the original C-13 atom. Ingestion of these C-nor-D-homosteroids results in birth defects in lambs:cyclopiafromcyclopamineand leg deformity from veratramine.[58]A further C-nor-D-homosteroid (nakiterpiosin) is excreted byOkinawancyanobacteriosponges.e.g.,Terpioshoshinota,leading to coral mortality from black coral disease.[59]Nakiterpiosin-type steroids are active against the signaling pathway involving thesmoothenedandhedgehogproteins, a pathway which is hyperactive in a number of cancers.[citation needed]

Biological significance

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Steroids and their metabolites often function assignallingmolecules (the most notable examples are steroid hormones), and steroids andphospholipidsare components ofcell membranes.[60]Steroids such as cholesterol decreasemembrane fluidity.[61] Similar tolipids,steroids are highly concentrated energy stores. However, they are not typically sources of energy; in mammals, they are normally metabolized and excreted.

Steroids play critical roles in a number of disorders, including malignancies likeprostate cancer,where steroid production inside and outside the tumour promotes cancer cell aggressiveness.[62]

Biosynthesis and metabolism

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Chemical-diagram flow chart
Simplification of the end of the steroid synthesis pathway, where the intermediatesisopentenyl pyrophosphate(PP or IPP) anddimethylallyl pyrophosphate(DMAPP) formgeranyl pyrophosphate(GPP),squaleneandlanosterol(the first steroid in the pathway)

The hundreds of steroids found in animals, fungi, andplantsare made fromlanosterol(in animals and fungi; see examples above) orcycloartenol(in other eukaryotes). Both lanosterol and cycloartenol derive fromcyclizationof thetriterpenoidsqualene.[4]Lanosterol and cycloartenol are sometimes called protosterols because they serve as the starting compounds for all other steroids.

Steroid biosynthesis is ananabolicpathway which produces steroids from simple precursors. A unique biosynthetic pathway is followed in animals (compared to many otherorganisms), making the pathway a common target forantibioticsand other anti-infection drugs. Steroid metabolism in humans is also the target of cholesterol-lowering drugs, such asstatins.In humans and other animals the biosynthesis of steroids follows the mevalonate pathway, which usesacetyl-CoAas building blocks fordimethylallyl diphosphate(DMAPP) andisopentenyl diphosphate(IPP).[63][better source needed]

In subsequent steps DMAPP and IPP conjugate to formfarnesyl diphosphate(FPP), which further conjugates with each other to form the linear triterpenoid squalene. Squalene biosynthesis is catalyzed bysqualene synthase,which belongs to thesqualene/phytoene synthase family.Subsequentepoxidationand cyclization of squalene generate lanosterol, which is the starting point for additional modifications into other steroids (steroidogenesis).[64]In other eukaryotes, the cyclization product of epoxidized squalene (oxidosqualene) is cycloartenol.

Mevalonate pathway

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Chemical flow chart
Mevalonate pathway
Main article:Mevalonate pathway

The mevalonate pathway (also called HMG-CoA reductase pathway) begins withacetyl-CoAand ends withdimethylallyl diphosphate(DMAPP) andisopentenyl diphosphate(IPP).

DMAPP and IPP donateisopreneunits, which are assembled and modified to formterpenesandisoprenoids[65](a large class of lipids, which include thecarotenoidsand form the largest class of plantnatural products).[66]Here, the isoprene units are joined to makesqualeneand folded into a set of rings to makelanosterol.[67]Lanosterol can then be converted into other steroids, such as cholesterol andergosterol.[67][68]

Two classes ofdrugstarget themevalonate pathway:statins(likerosuvastatin), which are used to reduceelevated cholesterol levels,[69]andbisphosphonates(likezoledronate), which are used to treat a number of bone-degenerative diseases.[70]

Steroidogenesis

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Chemical-diagram flow chart
Human steroidogenesis, with the major classes of steroid hormones, individual steroids andenzymaticpathways.[71]Changes in molecular structure from a precursor are highlighted in white.
See also:Steroidogenic enzyme

Steroidogenesis is the biological process by which steroids are generated from cholesterol and changed into other steroids.[72]Thepathwaysof steroidogenesis differ among species. The major classes of steroid hormones, as noted above (with their prominent members and functions), are theprogestogens,corticosteroids(corticoids),androgens,andestrogens.[25][73]Human steroidogenesis of these classes occurs in a number of locations:

Production rates, secretion rates, clearance rates, and blood levels of major sex hormones
Sex Sex hormone Reproductive
phase 		Blood
production rate 		Gonadal
secretion rate 		Metabolic
clearance rate 		Reference range (serum levels)
SIunits Non-SIunits
Men Androstenedione
–
 2.8 mg/day 1.6 mg/day 2200 L/day 2.8–7.3 nmol/L 80–210 ng/dL
Testosterone
–
 6.5 mg/day 6.2 mg/day 950 L/day 6.9–34.7 nmol/L 200–1000 ng/dL
Estrone
–
 150 μg/day 110 μg/day 2050 L/day 37–250 pmol/L 10–70 pg/mL
Estradiol
–
 60 μg/day 50 μg/day 1600 L/day <37–210 pmol/L 10–57 pg/mL
Estrone sulfate
–
 80 μg/day Insignificant 167 L/day 600–2500 pmol/L 200–900 pg/mL
Women Androstenedione
–
 3.2 mg/day 2.8 mg/day 2000 L/day 3.1–12.2 nmol/L 89–350 ng/dL
Testosterone
–
 190 μg/day 60 μg/day 500 L/day 0.7–2.8 nmol/L 20–81 ng/dL
Estrone Follicular phase 110 μg/day 80 μg/day 2200 L/day 110–400 pmol/L 30–110 pg/mL
Luteal phase 260 μg/day 150 μg/day 2200 L/day 310–660 pmol/L 80–180 pg/mL
Postmenopause 40 μg/day Insignificant 1610 L/day 22–230 pmol/L 6–60 pg/mL
Estradiol Follicular phase 90 μg/day 80 μg/day 1200 L/day <37–360 pmol/L 10–98 pg/mL
Luteal phase 250 μg/day 240 μg/day 1200 L/day 699–1250 pmol/L 190–341 pg/mL
Postmenopause 6 μg/day Insignificant 910 L/day <37–140 pmol/L 10–38 pg/mL
Estrone sulfate Follicular phase 100 μg/day Insignificant 146 L/day 700–3600 pmol/L 250–1300 pg/mL
Luteal phase 180 μg/day Insignificant 146 L/day 1100–7300 pmol/L 400–2600 pg/mL
Progesterone Follicular phase 2 mg/day 1.7 mg/day 2100 L/day 0.3–3 nmol/L 0.1–0.9 ng/mL
Luteal phase 25 mg/day 24 mg/day 2100 L/day 19–45 nmol/L 6–14 ng/mL
Notes and sources
Notes:"Theconcentrationof a steroid in the circulation is determined by the rate at which it is secreted from glands, the rate of metabolism of precursor or prehormones into the steroid, and the rate at which it is extracted by tissues and metabolized. Thesecretion rateof a steroid refers to the total secretion of the compound from a gland per unit time. Secretion rates have been assessed by sampling the venous effluent from a gland over time and subtracting out the arterial and peripheral venous hormone concentration. Themetabolic clearance rateof a steroid is defined as the volume of blood that has been completely cleared of the hormone per unit time. Theproduction rateof a steroid hormone refers to entry into the blood of the compound from all possible sources, including secretion from glands and conversion of prohormones into the steroid of interest. At steady state, the amount of hormone entering the blood from all sources will be equal to the rate at which it is being cleared (metabolic clearance rate) multiplied by blood concentration (production rate = metabolic clearance rate × concentration). If there is little contribution of prohormone metabolism to the circulating pool of steroid, then the production rate will approximate the secretion rate. "Sources:See template.

Alternative pathways

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In plants and bacteria, thenon-mevalonate pathway(MEP pathway) usespyruvateandglyceraldehyde 3-phosphateas substrates to produce IPP and DMAPP.[65][78]

During diseases pathways otherwise not significant in healthy humans can become utilized. For example, in one form ofcongenital adrenal hyperplasiaadeficiency in the 21-hydroxylase enzymatic pathwayleads to an excess of17α-Hydroxyprogesterone(17-OHP) – this pathological excess of 17-OHP in turn may be converted todihydrotestosterone(DHT, a potent androgen) through among others17,20 Lyase(a member of thecytochrome P450family of enzymes),5α-Reductaseand3α-Hydroxysteroid dehydrogenase.[79]

Catabolism and excretion

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Steroids are primarily oxidized bycytochrome P450 oxidaseenzymes, such asCYP3A4.These reactions introduce oxygen into the steroid ring, allowing the cholesterol to be broken up by other enzymes into bile acids.[80]These acids can then be eliminated by secretion from theliverinbile.[81]The expression of theoxidasegene can beupregulatedby the steroid sensorPXRwhen there is a high blood concentration of steroids.[82]Steroid hormones, lacking the side chain of cholesterol and bile acids, are typicallyhydroxylatedat various ring positions oroxidized at the 17 position,conjugatedwith sulfate orglucuronic acidand excreted in the urine.[83]

Isolation, structure determination, and methods of analysis

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Steroidisolation,depending on context, is the isolation of chemical matter required forchemical structureelucidation, derivitzation or degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but often more[84]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.[85][page needed]

The methods of isolation to achieve the two scales of product are distinct, but includeextraction,precipitation,adsorption,chromatography,andcrystallization.In both cases, the isolated substance is purified to chemical homogeneity; combined separation and analytical methods, such asLC-MS,are chosen to be "orthogonal" —achieving their separations based on distinct modes of interaction between substance and isolating matrix—to detect a single species in the pure sample.

Structure determinationrefers to the methods to determine the chemical structure of an isolated pure steroid, using an evolving array of chemical and physical methods which have includedNMRand small-moleculecrystallography.[2]: 10–19 Methods of analysisoverlap both of the above areas, emphasizing analytical methods to determining if a steroid is present in a mixture and determining its quantity.[85]

Chemical synthesis

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Microbialcatabolismofphytosterolside chainsyields C-19 steroids, C-22 steroids, and17-ketosteroids(i.e.precursorstoadrenocortical hormonesandcontraceptives).[86][87][88]The addition and modification offunctional groupsis key when producing the wide variety of medications available within this chemical classification. These modifications are performed using conventionalorganic synthesisand/orbiotransformationtechniques.[89][90]

Precursors

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Semisynthesis

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Thesemisynthesisof steroids often begins from precursors such ascholesterol,[88]phytosterols,[87]orsapogenins.[91]The efforts ofSyntex,a company involved in theMexican barbasco trade,usedDioscorea mexicanato produce the sapogenindiosgeninin the early days of the synthetic steroidpharmaceutical industry.[84]

Total synthesis

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Some steroidal hormones are economically obtained only bytotal synthesisfrompetrochemicals(e.g. 13-alkylsteroids).[88]For example, the pharmaceuticalNorgestrelbegins frommethoxy-1-tetralone,a petrochemical derived fromphenol.

Research awards

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A number ofNobel Prizeshave been awarded for steroid research, including:

See also

[edit]

References

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  3. ^Rhen T, Cidlowski JA (October 2005). "Antiinflammatory action of glucocorticoids--new mechanisms for old drugs".The New England Journal of Medicine.353(16): 1711–1723.doi:10.1056/NEJMra050541.PMID16236742.S2CID5744727.
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