Anabolic steroidSteroidany of a class of natural or synthetic organic compounds characterized by a molecular structure of 17 carbon atoms arranged in four rings. Steroids are important in biologychemistryand medicine. The steroid group includes all the sex hormonesadrenal cortical hormones, bile acids, and sterols of vertebrates, as well as the molting hormones of insects anabolic steroids chemical name many other physiologically active substances of animals and plants. Among the synthetic steroids of therapeutic value are a large number of anti-inflammatory agents, anabolic growth-stimulating agents, and oral contraceptives. Different categories of steroids are frequently distinguished from each other by names that anabolic steroids tiger blood products to their biological source—e. Steroids vary from one another in the nature of attached groups, the position anabolic steroids chemical name the groups, and the configuration of the steroid nucleus or gonane. Small modifications in the molecular structures of steroids can produce remarkable differences in their biological activities.
Chemistry and Structure of Anabolic and Androgenic Steroids
Steroid , any of a class of natural or synthetic organic compounds characterized by a molecular structure of 17 carbon atoms arranged in four rings. Steroids are important in biology , chemistry , and medicine. The steroid group includes all the sex hormones , adrenal cortical hormones, bile acids, and sterols of vertebrates, as well as the molting hormones of insects and many other physiologically active substances of animals and plants.
Among the synthetic steroids of therapeutic value are a large number of anti-inflammatory agents, anabolic growth-stimulating agents, and oral contraceptives.
Different categories of steroids are frequently distinguished from each other by names that relate to their biological source—e. Steroids vary from one another in the nature of attached groups, the position of the groups, and the configuration of the steroid nucleus or gonane. Small modifications in the molecular structures of steroids can produce remarkable differences in their biological activities.
This article covers the history, chemistry, biological significance, and basic pharmacology of steroids. For more information about the physiological relevance and the pharmacological applications of steroids, see human endocrine system , endocrine system , and drug. The first therapeutic use of steroids occurred in the 18th century when English physician William Withering used digitalis , a compound extracted from the leaves of the common foxglove Digitalis purpurea , to treat edema.
Studies of steroids commenced in the early 19th century with investigations of the unsaponifiable i. This early work, with which many of the noted chemists of the time were associated, led to the isolation of cholesterol and some bile acids in reasonable purity and established some significant features of their chemistry. Insight into the complex polycyclic steroid structure, however, came only after the beginning of the 20th century, following the consolidation of chemical theory and the development of chemical techniques by which such molecules could be broken down step by step.
Arduous studies, notably by the research groups of German chemists Adolf Windaus and Heinrich Wieland , ultimately established the structures of cholesterol; of the related sterols, stigmasterol and ergosterol ; and of the bile acids.
Investigation of ergosterol was stimulated by the realization that it can be converted into vitamin D. Only in the final stages of this work was the arrangement of the component rings of the nucleus clarified by results obtained by pyrolytic heat-induced bond-breaking dehydrogenation and X-ray crystallography.
With the foundations of steroid chemistry firmly laid, the next decade saw the elucidation of the structures of most of the physiologically potent steroid hormones of the gonads and the adrenal cortex. Added impetus was given to steroid research when American physician Philip S.
Hench and American chemist Edward C. Kendall announced in that the hitherto intractable symptoms of rheumatoid arthritis were dramatically alleviated by the adrenal hormone cortisone.
New routes of synthesis of steroids were developed, and many novel analogs were therapeutically tested in a variety of disease states. From these beginnings has developed a flourishing steroid pharmaceutical industry —and with it a vastly expanded fundamental knowledge of steroid reactions that has influenced many other areas of chemistry. Knowledge of the biochemistry of steroids has grown at a comparable rate, assisted by the use of radioisotopes and new analytical techniques.
The metabolic pathways sequences of chemical transformations in the body , both of synthesis and of decomposition, have become known in considerable detail for most steroids present in mammals , and much research relates to control of these pathways and to the mechanisms by which steroid hormones exert their effects. The hormonal role of steroids in other organisms is also of growing interest. All steroids are related to a characteristic molecular structure composed of 17 carbon atoms—arranged in four rings conventionally denoted by the letters A , B , C , and D —bonded to 28 hydrogen atoms.
This parent structure 1 , named gonane also known as the steroid nucleus , may be modified in a practically unlimited number of ways by removal, replacement, or addition of a few atoms at a time; hundreds of steroids have been isolated from plants and animals, and thousands more have been prepared by chemical treatment of natural steroids or by synthesis from simpler compounds.
The steroid nucleus is a three-dimensional structure, and atoms or groups are attached to it by spatially directed bonds. Although many stereoisomers of this nucleus are possible and may be synthesized , the saturated nuclear structures of most classes of natural steroids are alike, except at the junction of rings A and B.
Simplified three-dimensional diagrams may be used to illustrate stereochemical details. In the cis isomer, bonds to the methyl group , CH 3 , and to the hydrogen atom, H, both project upward from the general plane defined by the rest of the molecule , whereas in the trans isomer, the methyl group projects up and the hydrogen projects down.
Usually, however, steroid structures are represented as plane projection diagrams such as 4 and 5, which correspond to 2 and 3, respectively. Groups attached to unsaturated carbons lie in the same plane as the adjacent carbons of the ring system as in ethylene , and no orientation need be specified.
Each carbon atom of a steroid molecule is numbered, and the number is reserved to a particular position in the hypothetical parent skeletal structure 6 whether this position is occupied by a carbon atom or not.
Steroids are named by modification of the names of skeletal root structures according to systematic rules agreed upon by the International Union of Pure and Applied Chemistry. By attaching prefixes and suffixes to the name of the appropriate root structure, the character of substituent groups or other structural modification is indicated.
In addition to differences in details of the steroid nucleus, the various classes of steroids are distinguished by variations in the size and structure of an atomic group the side chain attached at position For brevity in discussion and in trivial nomenclature , a number of prefixes are often attached, with locants, to the names of steroids to indicate specific modifications of the structure.
In addition to the usual chemical notations for substituent groups replacing hydrogen atoms e. Depending on the number and character of their functional groups, steroid molecules may show diverse reactivities. An important property of steroids is polarity —i. Hydroxyl, ketonic, or ionizable capable of dissociating to form electrically charged particles groups in a steroid molecule increase its polarity to an extent that is strongly influenced by the spatial arrangement of the atoms within the molecule.
Procedures for isolation of steroids differ according to the chemical nature of the steroids and the scale and purpose of the isolation.
Steroids are isolated from natural sources by extraction with organic solvents, in which they usually dissolve more readily than in the aqueous fluids of tissues. The source material often is treated initially with an alcoholic solvent, which dehydrates it, denatures renders insoluble proteins associated with the steroids, and dissolves many steroids. Saponification either of whole tissues or of substances extracted from them by alcohol splits the molecules of sterol esters , triglycerides , and other fatty esters and permits the extraction of the sterols by means of water-immiscible solvents, such as hexane or ether , with considerable purification.
Intact sterol esters or hormonal steroids and their metabolites compounds produced by biological transformation that are sensitive to strong acids or alkalies , however, require essentially neutral conditions for isolation, and, although some procedures for analysis of urinary steroids employ acid treatment, milder hydrolysis , as by enzymes , is preferred. The acidity of some steroids allows them to be held in alkaline solution , while nonacidic impurities are extracted with organic solvents.
Commercially, abundant steroids usually are purified by repeated crystallization from solvents. Small-scale laboratory isolations for investigative or assay purposes usually exploit differing polarities of the steroid and of its impurities, which may be separated by partitioning between solvents differing in polarity or by chromatography see below Determination of structure and methods of analysis.
Occasionally, special reagents may selectively precipitate or otherwise sequester the desired steroid. New steroids of great physiological interest often are isolated from tissue only with extreme difficulty, because they are usually trace constituents.
In one example, kg 1, pounds of silkworm pupae yielded 25 mg 0. In such cases each isolation step is followed by an assay for the relevant physiological activity to ensure that the desired material is being purified.
The percentage recovery of known steroid hormones during their assay in small biological samples usually is assessed by adding a trace of the same steroid in radioactive form to the initial sample, followed by radioassay analysis based on radioactivity after purification is complete.
The efficiency of recovery of the radioactive steroid is assumed to be the same as that of the natural substance. The systematic, stepwise breakdown by chemical methods of the steroid ring systems, used in early investigations of structure, is mainly of historical interest. The small number of different nuclear structures found in steroids often has permitted establishment of the structure of a new steroid by conversion to related compounds of known structure.
Structure elucidation in the steroid field, as in all areas of organic chemistry, depends heavily on physical methods, particularly nuclear magnetic resonance , infrared spectroscopy , mass spectrometry , and X-ray crystallography. Data obtained by these methods reinforce and often replace the classical criteria of characterization of steroids: Chromatography is a crucial technique in steroid chemistry.
The behaviour of a steroid in selected chromatographic systems often identifies it with a high degree of probability. The identification may be made virtually certain by the conversion of the material to derivatives that in turn are examined chromatographically. Abundant data for the behaviour of steroids in paper chromatography , thin-layer chromatography , liquid chromatography , and gas-liquid chromatography show that individual features of molecular structure determine the chromatographic properties of steroids in a predictable manner.
The gas-liquid chromatograph or liquid chromatograph linked directly to the mass spectrometer permits characteristic mass-spectral fragmentation patterns and critical gas-liquid chromatographic data to be obtained simultaneously, using a sample containing less than a microgram of a steroid. This powerful technique is of growing importance in the structural analysis of steroids in extracts of such body fluids as blood and urine.
In most total syntheses of steroids, a monocyclic starting material such as a quinone provides one ring upon which the other rings of the nucleus are elaborated step-by-step by condensation reactions with smaller molecules to give the desired stereochemistry in successive ring fusions.
Each new ring closure must also provide functional groups that can be used in building up the next ring. In a quite different approach, stereochemical control of ring fusions is achieved by using the fact that under acidic conditions open-chain molecules containing suitably located double bonds cyclize to multiring structures that have the necessary stereochemistry and that can be relatively easily converted to steroids.
From its analogy with the cyclization of squalene 2,3-oxide to lanosterol in the biosynthesis of cholesterol see below Biosynthesis and metabolism of steroids: Cholesterol , this method is said to involve biogenetic-type cyclization.
Although total synthesis of steroids has proved commercially feasible , it is often more practical to prepare them by partial synthesis—that is, by modification of other naturally abundant steroids. To be useful as a starting material for partial synthesis, the naturally occurring steroid must possess a molecular structure that can be easily converted to that of the desired product.
For the synthesis of cortisol , cortisone , and their analogs, which carry an oxygen function at C11, a preexisting oxygen function at this position or at the adjacent C12 is highly desirable. Indeed, prior to the advent of methods for microbiological oxidation, this was a crucial requirement, since the introduction of any functional group at C11 of most steroids was extremely difficult.
In the early commercial synthesis of androgenic steroids, cholesterol was the main starting material. Cholic acid and deoxycholic acid, inexpensive by-products from slaughterhouses, were starting materials for production of cortisone. Today most steroid drugs are manufactured from the abundant steroids of plant origin, notably the sapogenins.
Diosgenin, obtainable from several varieties of yams in the genus Dioscorea , is used in the commercial manufacture of progesterone. Progesterone can be converted to androgenic and estrogenic hormones and to the more complex adrenal steroid hormones , such as cortisone and cortisol.
A most important advance in this field was the discovery that microorganisms such as Rhizopus nigricans introduce hydroxyl groups into a variety of steroids at C11 and elsewhere: A sapogenin , hecogenin, obtainable in quantity from the waste of sisal plants, is used for synthesis of cortisol. Stigmasterol, which is readily obtainable from soybean oil , can be transformed easily to progesterone and to other hormones, and commercial processes based on this sterol have been developed.
That such diverse physiological functions and effects should be exhibited by steroids, all of which are synthesized by essentially the same central biosynthetic pathway, is a remarkable example of biological economy. Most of these functions, especially those of a hormonal type, involve the transmission of biologically essential information.
The specific information content of the steroid resides in the character and arrangement of its substituent groups and in other subtle structural modifications. The most generally abundant steroids are sterols, which occur in all tissues of animals , green plants , and fungi such as yeasts. Evidence for the presence of steroids in bacteria and in primitive blue-green algae is conflicting. The major sterols of most tissues are accompanied by traces of their precursors—lanosterol in animals and cycloartenol in plants—and of intermediates between these compounds and their major sterol products.
In mammalian skin one precursor of cholesterol , 7-dehydrocholesterol, is converted by solar ultraviolet light to cholecalciferol , vitamin D 3 , which controls calcification of bone by regulating intestinal absorption of calcium.
The disease rickets , which results from lack of exposure to sunlight or lack of intake of vitamin D , can be treated by administration of the vitamin or of the corresponding derivative of ergosterol , ergocalciferol vitamin D 2.
Sterols are present in tissues both in the nonesterified free form and as esters of aliphatic fatty acids. In the disease atherosclerosis , fatty materials containing cholesterol form deposits plaques , especially in the walls of the major blood vessels , and vascular function may be fatally impaired. The disease has many contributory factors but typically is associated with elevated concentrations of cholesterol in the blood plasma.
One aim of medical treatment is to lower the plasma cholesterol level. Free sterols appear to stabilize the structures of cellular and intracellular membranes.
Because the sheath of nerve fibres is a deposit of many layers of the membranes of neighbouring cells, mature mammalian nerve tissue e. Cholesterol also is converted in animals to steroids that have a variety of essential functions and in plants to steroids whose functions are less clearly understood. The bile acids cholanoic acids, also called cholanic acids of higher vertebrates form conjugates with the amino acids taurine and glycine , and the bile alcohols cholane derivatives of lower animals form esters with sulfuric acid sulfates.