3076966 steroids and its biological activity

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MF108 Structural Biochemistry ______________________________________________

1.0 INTRODUCTIONS

1.1 General structural properties of steroids

Steroid is a compound that contains the ring system which contains four rings that

are named 1,2-cyclopentano-perhydrophenantrene and each ring is designated to A, B, C

and D accordingly. The numbering of the carbons should start with ring A, B, C and D.

The carbon are numbered as shown in the diagram below, starting from ring A and

subsequently progressing the numbering to ring D, then to the angular (bridgehead)

methyl groups usually on position carbon 10 and 13 and finally to side chain linked to the

carbon 17.

The naming of the particular steroids can be differ by varying the steroid nucleus

with different side chains. Most of the steroids may be named based on the derivatives of

this structure, which is called cholestane shown in the above figure. It is to say that all

steroids share similar chemistry & nomenclature due to its structural similarities as

steroid ring with common numbering system present. Therefore, if there is small changes

in structure can dramatically affect the conformation and configuration of the molecule.

The presence of different location of different substituents in the ring system will

then influence the pharmacological & physiological activity of the steroid.

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1.2 Stereochemistry of steroids

The interesting feature of the steroid stereochemistry is that the six-membered

rings can present in fixed chair conformations. The two cyclohexane rings can be joined

in either a cis or a trans conformation. In cis-decalin, both groups at the ring-junction

positions are on the same side of the two rings. However, in trans-decalin, the groups at

the ring junctions are on opposite sides. Theoretically the trans isomer is more stable in

the structure. The four fused-ring structure can have three dimensional structures in its

configurational isomers as the following figure:

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2.0 CLASSIFICATION OF STEROIDS

2.1 Animal steroids

2.1.1 Insect steroids

Metamorphosis hormones: Ecdysteroids such as ecdysterone.

2.1.2 Animal steroids

Sterol (cholesterol, stigmasterol and vitamin D3)

Bile acid and bile salt

Steroid hormones

Sex hormones

i. Female sex hormones

- Estrogen

- Progestins(progesterone)

ii. Male sex hormones (androgen)

- Testosterone,

- Anabolic steroids

Adrenal cortex hormones (corticosteroids)

- Glucocorticoids (cortisol or hydrocortisone and cortisone)

- Mineralocorticoids (aldosterone)

2.2 Plants steroids

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Phytosterols

Brassinosteroids

2.3 Fungus steroids Ergosterols

2.4 Synthetic drugs of steroids

Cardiac glycosides (digitalis)

Prednisolone

3.0 STRUCTURAL CHEMISTRY OF DIFFERENT TYPES OF STEROIDS

3.1 Sterol

Sterol is one of group of steroid alcohol with multi-ring structure and it is the

derivatives of steroids with hydroxyl group attached to the carbon 3 of the ring A. This

hydrocarbon side chain can poses the polarity in the structure. The alipathic chain

including the four ring system shows hydrophobicity or non-polar properties. Thus it is

considered as the amphipathic lipids since the structure can have both hydrophilic and

hydrophobic characteristics. It can be esterified into thelipid bilayers of the cell

membrane. However, sterols onlyexist in the membranes ofeukaryotes, none of the

plants have sterols in membranes except mycoplasmas. The following diagram indicates

the association of the sterol molecules with the amphipathic cytoplasmic membrane.

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We can say that the overall structure results in the water insolubility of the

compound as there is only one ionizable residue present in the structure. Sterols and their

fatty-acid estersare essentially waterinsoluble. Sterols sometime contain one or more

double bonds in the ring structure and there are also a variety of substituents attached to

the rings. In eukaryoticorganisms, sterol is most represented by cholesterol and

ergosterol (yeast). Besides, stigmasterol is the most common phytosterol in plants.

3.2 Cholesterol

Cholesterol has a molecular formula of C27H45OH and it is composed of a

hydrocarbon tail ring structure with 4 hydrocarbon rings as well as a hydroxyl group

attached to the carbon 3. The hydroxyl group is polar, which makes it soluble in water

and it can exert some alcoholic characteristics. The 4-ring region of cholesterol is the

significant of all steroids. Each corner of the ring is composed of a carbon atom, with

extending two hydrogen atoms. Cholesterol is regarded as "sterol" in response to the

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combination of the steroid ring structure and the hydroxyl group. Basically, cholesterol is

the animal sterol since there are small amounts of cholesterol made in plants. The

hydrocarbon tail is composed of carbon and hydrogen atoms like the steroid. Both the

ring region and tail region are non-polar, this is the reason why they are capable of

dissolving in fatty and oily substances but is not soluble with water. This make the

structure become amphipathic as both a water-soluble region and a fat-soluble region

present in the structure.

3.3 Vitamin D

Vitamin D which is called as calciferol and it is a fat-soluble vitamin since it can

be synthesized from cholesterol. The figure above shows the structures of vitamin D2

(ergocalciferol) and vitamin D3 (cholecalciferol).

3.4 Bile acid and bile salts

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Bile secretion is carried out in the liver and stored in the gall bladder. It is made

up of the bile acids or bile salts which contains cholic acid and chenodeoxycholic acid.

Both compounds show rigid steroid nucleus and a short aliphatic side chain. Thisinvolves 3 six-member rings (A, B and C) and a five member ring (D). The angular

methyl groups are present at positions C-18 and C-19. The classification of the structure

is based on the side chain of the compound. Cholic acid has an extra hydroxyl residue

attached at position C-12 in ring C comparing to chenodeoxycholic acid due to the

different synthesis pathway from cholesterol. Bile acids are amphipathic which contain

both hydrophobic (lipid soluble) and hydrophilic (polar) properties.

3.5 Female Sex Hormone

3.5.1. Estrogen

Estrogen is derived from terpenes and it carries with 4 condensed rings like others

steroid derivatives. A rings has a hydroxyl group and oxygen substituent present while the

D ring is extending with an alkyl chain. The classic estrogens are estrone, 17-

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estradiol (most potent), and estriol. Estrogen shows the absence of methyl group in C19

and surprisingly ring A indicates aromatic characteristics.

3.5.2. Progestins

Progesterone is the model molecule of sex hormones. It consists of four

interconnected cyclic hydrocarbons. There are ketone and oxygenated functional groups

with two methyl branches exit in the structure. It is hydrophobic in nature.

3.6 Male Sex Hormone

3.6.1. Testosterone

Testosterone naturally produced in the human body has the chemical formula C19H28O2.

Testosterone is referred as a "bioidentical hormone" which represents the similar

chemical structure to natural synthesized hormone. However, chemical modification in

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the testosterone molecule by adding a side chain or functional group will produce

"synthetic" hormone such as methyltestosterone and some anabolic steroids.

Androgenic steroid can give effects in the male secondary sexual characterization and

male reproductive tract development.

3.7 Adrenal cortex hormones

Theoretically, these compounds should be formed in the adrenal cortex.

Furthermore, they must be C-21 steroids and three or more oxygen atoms. They have all a

en-4-one-3 group and an oxygenated function at C-20.

3.7.1. Glucocorticoids

Cortisol has a general formula of C21H30O5 and it has a hydroxyl group at C-11, C-

17, and C-21. It is produced by the adrenal cortex which regulates carbohydrate

metabolism and controls blood pressure. Cortisol can be used to treat inflammatory

conditions and adrenal failure. It may convert to hydrocortisol or cortisone when

undergoing the metabolism.

3.7.2. Mineralocorticoids

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Aldosterone has one hydroxyl group at C-11 and one aldehyde function at C-18.

4.0 BIOLOGICAL ACTIVITY AND PHYSIOLOGICAL FUNCTIONS OF

STEROIDS

4.1 Cholesterol

Sterols are widely distributed and embedded in cell membrane as if in the figure

above. Modifications of the steroid ring structure are made by specific enzyme systems,

producing the sterol characteristic for each species, such asergosterol in yeast. The

major regulatory step in the sterol biosyntheticpathway occurs early in the process.

Drugs that lower blood cholesterol levels in humans are designed to inhibit this

regulatory enzyme. In addition to their conversion to sterols, several intermediates in the

pathway are precursors of other important biological compounds, including chlorophyll

in plants, vitamins A, D, E, and K, and regulators of membrane functions and metabolic

pathways.

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For example cholesterol forms part of the cellular membrane where its presence

affects the cell membrane's fluidity and serves as secondary messengerin

developmental signaling. Cholesterol also serves as a precursor of steroidhormones

(estrogens, androgens, glucocorticoids, and mineralocorticoids) and bile acids.

Cholesterol can serve as precursor of all type of steroids.

4.1.1. Maintains the integrity of the cell membranes

Cholesterol is an amphipathic molecule which contains a hydrophilic (hydroxyl,

OH groups) and a hydrophobic (hydrocarbon tail) portion. The hydrophilic portion of

cholesterol aligns with the phosphate heads of the phospholipids while the remaining

portion of it tucks into the fatty acid portion of the membrane. Due to the way how

cholesterol is shaped, part of the steroid ring, the four hydrocarbon rings in between the

hydroxyl group and the hydrocarbon "tail", is closely attracted to part of the fatty acid

chain on the nearest phospholipid. This helps immobilize the outer surface of the

membrane slightly and make it less soluble to very small water-soluble molecules that

could otherwise pass through the membrane more easily.

4.1.2. Helps maintain the fluidity of the cell membranes

It helps in preventing the fatty acid chains in the cell membrane from packing

together and crystallizing by separating the phospholipids when there is high

concentration of cells in the body fluids and thus provides a consistency to the cell

membranes.

4.1.3. Helps secure important proteins in the cell membrane

The lipid rafts in membranes contain cholesterol with longer and more saturated

fatty acid tails. Due to the shape of the cholesterols, they aggregate more in the

membrane which leads to the increase of the thickness of the membrane making it ideal

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for accommodating certain proteins that require special condition to function properly

like sticking with other proteins to carry out their functions.

4.1.4. Arteriosclerosis and cholesterol

Cholesterol is the most widespread animal steroid and found in almost all animal

tissues. For example, egg yolks are rich resource of this compound. Cholesterol is an

important component of cell membranes and can serve as intermediate in the biosynthesis

of the steroid hormones. However, because it can be synthesized from acetyl coenzyme

A, it is usually not a dietary necessity. High levels of cholesterol in blood are associated

with atherosclerosis (hardening of the arteries). This condition involves the accumulation

of cholesterol and other lipids in the lumen of the arteries.

Figure: Plaque formation on the arteries.

Lipoproteins play important roles in the arteriosclerosis disease. It is the carrier

for cholesterol and can be classified into HDL(high-density lipoprotein) and LDL(low-

density lipoprotein). It's often said that HDL is the good cholesterol and LDL is the bad

cholesterol. The elevation of the LDL level will deposit the plaque formation on the

arteries wall. It results in familial hypercholesterolemia which associates with the LDL

defect. The narrowing of arteries will lead to the blockage of the blood flow and cause the

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blood pressure become higher. This abnormal blood flow will cause the arteriosclerosis to

occur.

4.2. Vitamin D

Figure: Biosynthesis activation of cholecalciferol and ergocalciferol by ultraviolet light.

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The general structure represents the rings A, B, C, and D with differing side chain

residues. Basically, vitamin D3 which is found in human is considered as a seco-steroid

which involved the ring opening during the synthesis process. The 7-dehydrocholesterol

found in the skin and converted to vitamin D when in contact with ultraviolet light. This

process involves the bond breakage that happens in the carbon-9 and 10 in ring B with

the presence of ultraviolet light. The conjugated double bond system in the molecule

permits the light absorption of UV light at certain wavelengths. This initiates the structure

transformations and consequently results in the production of vitamin D3. This can

normally occur in the epidermis or skin of most animals.

For instance, the exposure of the sunlight is a better way to nourish our body with

vitamin D rather than the dietary requirement for this kind of vitamin. Vitamin D can

enhance the calcium and phosphorus which can promote their absorption from the skin

and deposition in the bone. Poor diet or lack of sunlight can cause rickets and

osteomalacia due to the vitamin D deficiency.

4.2.1. Promotes immune function in the skin

During wound healing, the expression of the antimicrobial peptide cathelicidin,

which can be induced in keratinocytes in vitro by vitamin D3 increases. Besides, the

vitamin D3 also induces the expression of Toll-like receptor 2 (TLR2) and the Toll-like

receptor cofactor CD14 in wounds and vitro. The increase in TLR2 expression allows

keratinocytes to respond to microbial stimulation and also generates an amplification

loop, the TLR2 signalling leads to increased expression of 1 -hydroxylase (which is the

enzyme that catalysts the conversion of inactive vitamin D3 to active form), and therefore

more production of active vitamin D3, which induces the expression of cathelicidin and

enhances the expression of TLR2.

4.2.2. Increases the serum calcium concentrations

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When the concentration of calcium ions is very low in the body, the parathyroid

hormone is induced which in turn stimulates the activation of vitamin D3. The active

form vitamin D3 will stimulate the increase of calcium absorption in intestine, increasing

osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. If the

calcium ions concentration is too high in the body, the active form vitamin D3 will be

suppressed which lead to the decrease in absorption of calcium ions and increase in the

excretion of excess calcium ions

4.3. Bile acid and bile salts

The metabolism allows cholic and chenodeoxycholic acid to be conjugated with

glycine or taurine to give the product of bile salt, which is the conjugated form of bile

acids

The metabolism allows cholic and chenodeoxycholic acid to be conjugated with

glycine or taurine to give the product of bile salt, which is the conjugated form of bile

acids.

4.3.1 Facilitate digestion and absorption of lipid

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They are emulsifying agents that have amphipathic molecules with both water-

soluble (hydroxyl groups, OH) and water-insoluble or fat-soluble (methyl groups, CH3)

parts that make them able to mix fats with water. These groups allow bile acids and salts

to break up large globs of fat, connecting to the fat on one side, and connecting to the

water on the other, thus mixing the fats and water together by wrapping around the fats.

The emulsifying process has increased the surface area of fats and making it available for

the digestion enzymes, lipases that are water soluble and cannot access the inside of lipid

droplets.

4.3.2 Solubilize and transport lipids in an aqueous environment

Their amphipathic nature has enabled them to carry the lipids and solubilize lipids

by forming micelles with phosphatidylcholine which are aggregates of lipids such as fatty

acids, cholesterol and monoglycerides that remain suspended in water.

4.4. Female Sex Hormone

4.4.1. Estrogen

Estrogen refers as the primary female sex hormone. It is present in both men and

women, but level of estrogen is higher in female. They stimulate female secondary sex

characteristics development, particularly in breasts, thickening of the endometrium and

their roles in the menstrual cycle. Follicle stimulating hormone (FSH) and luteinizing

hormone (LH) are the key hormone that control the secretion of estrogen.

4.4.1. (i) Stimulate protein synthesis.

It stimulates protein synthesis by entering the target cells and binds to a specific

receptor molecule to form a complex. The complex is then altered in such a way that it

can enter the cell nucleus and bind to nuclear components to promote the transcription of

specific messenger RNA (mRNA) which is then translated into specific proteins.

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4.4.1. (ii) Promotes secondary growth of female sex characteristics

The development of secondary female sex characteristics are stimulated by the

estrogens via the promotion of the accumulation of fats at the breast, hips, buttocks and

so on.

4.4.1. (iii) Prevent the development of osteoporosis

Estrogen blocks the activation of the bone metabolic unit and its effects may be

mediated in part by growth factors and interleukins. The estrogen prevents the

development of osteoporosis by blocking the synthesis of interleukin 6 which is a potent

stimulator of bone resorptions by osteoblast.

4.4.2. Progestins

Progesterone has similar pharmacological actions as estrogen. The target sites of

this hormone basically will be in the uterus, breast and brain can be done. The

development of the secondary endometrium can be done by progesterone. It usually takes

part at the end of the menstrual cycle. Progesterone enhances the cervical secretion and

reducing cervical penetration by sperm. Progesterone can decrease the contraction of the

uterus and thus promote the maintenance of pregnancy. Besides, by the aids of estrogen,

it is capable of stimulating the breast lactation during pregnancy. It is to notice that

testosterone and estrogen can be made from progesterone as well.

4.4.2. (i) Increase relaxation and reduce anxiety

In the brain, the progesterone provide a soothing effect in such a way that is

similar to the effects of benzodiazepins by a direct effect on neurotransmitter receptors

called Gamma-Amino Butyric Acid type A (GABAA) receptors. The action of

progesterone on GABAA receptors has been associated with an increase in appetite and

food intake.

4.4.2. (ii) Provide metabolic and nutritional effects

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It opposes the effect of estrogen in the tendency of storing fat by promoting the

use of fat for energy. It also normalizes blood sugar levels by interfering with the action

of insulin and counters the binding of estrogen with zinc and copper.

4.4.2. (iii) Involve in treatment of thyroid dysfunction

It counteracts the inhibition of thyroid hormone actions by estrogen via keeping

zinc and potassium in cells. The keeping of zinc and potassium in cells is important to

allow the entrance of thyroid hormone that will be converted into its active form, T3 to

carry out its function in the cells.

4.5. Male Sex Hormone

4.5.1. Testosterone

Testosterone poses virilizing and anabolic effects Anabolic effects include growth

of muscle mass and strength, increased bone density and strength, and stimulation of

height growth and bone maturation. Virilizing effect associates with the sex organ

maturation especially in penis and scrotum formation in fetuses and at puberty and voice

deepening.

4.5.1. (i) Promote erection

Testosterone is the precursor of the formation of dihydrotestosterone (DHT)

which is the regulator of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP).

Both of these compounds involve in the relaxation of smooth muscle that controls the

blood vessels within the penis. When the smooth muscles in the tissues of penis relax, the

tissues become engorged with bloods and this leads to the erection of penis.

4.5.1. (ii) Protect the brain against Alzheimers disease

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The brain is protected against Alzheimers disease through the inhibition of two

hallmarks of Alzheimers disease pathology, -amyloidfound in senile plaques and

hyperphosphorylated tau found inneurofibrillary tangles, by testosterone. The

testosterone reduces -amyloid secretion in cortical neurons by altering the processing of

the amyloid precursor protein.

4.5.2. Anabolic steroids

The term anabolic is derived from Greek word, it gives the meaning of build

up. Some references use the term anabolic-androgenic steroids (AAS) to represent

anabolic steroids. Nitrogen-retaining effects of androgen can boost the development of

the large muscle mass in males. This is because it has a protein building property which

leads to an increase in muscle strength. If comparing the testosterone and anabolic

steroid, both of them can play different roles of functional properties in our body.

Androgenic activity is essential for male sex drive and performance. It improves

secondary sexual characteristics development and play roles in spermatogenesis.

Anabolic activity enhances muscle mass development, strength, or endurance. It

sometimes functions in the reversion of catabolic process or tissue-depleting conditions.

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4.5.2. (i) Help patients gain weight after a severe illness, injury or continuing

infection

It helps to increase the bodys ability to use proteins to make muscle by sending

the amino acids which are the building blocks of proteins needed by muscle to grow back

to the muscles. It also prevents the breakdown of muscle and enhances recovery by

inhibiting the binding of cortisol (a stress hormone that is secreted during exercise to

enhance the use of proteins for fuel and to suppres inflammation that accompanies tissue

injury) to its receptor sites during and after exercise.

4.6. Adrenal cortex hormones

4.6.1. Glucocorticoids

Glucocorticoids can be secreted by the outer part of the adrenal gland. It is

released during stress conditions and has strong anti-inflammatory actions.

4.6.1. (i) Protects the brains

Under stress conditions, cortisol stimulates the breakdown of the structural and

functional proteins instead of the brain fats to release amino acids to provide the body

energy. These amino acids are then converted into useable carbohydrate (glucose) via the

process of gluconeogenesis in the liver. It also inhibits the transport of amino acids into

other types of cells and inhibits glucose uptake and oxidation by other cells.

4.6.1. (ii) Helps fight inflammation to minimize cellular damage

The cortisol controls the level of inflammation of injuries by influencing the

functions of lymphocytes, macrophages and leukoctyes with the utilization of energy to

direct their movement to specific locations. Beside that, it also inhibits the production of

some cytokines such as interleukin-1 and mediates several components of the

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inflammatory response. As a result, destruction of the cells caused by inflammatory

response can be minimized.

4.6.1. (iii) Decrease inflammation responses

Cortisone decreases inflammation (swelling) by preventing infection-fighting

white blood cells (leukocytes) from traveling to the area of swelling in the body. For

example, in the spine, brain or bone, it can decrease the pressure formed by the

inflammation responses on nerve endings and relieve pain.

4.6.2. Mineralocorticoids

Figure: Angiotensin and renin action on blood pressure regulation.

Aldosterone has important functions in regulating the electrolyte balance in body.

The location of action is mainly kidney and it functions to reduce the rate of sodium-ionexcretion with water retention. This will increase the rate of potassium-ion excretion.

The secretion of aldosterone appears to be regulated by two mechanisms. When the

concentration of dietary sodium ions is limited, rates of aldosterone secretion will be

increased. If there is reduced blood flow happens, it stimulates kidney cells to produce

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the renin, a proteolytic enzyme. It functions in converting the inactive angiotensinogen

globulin into angiotensin I(active). After angiotensin I convert into angiotensin II by

another enzyme, this promote the aldosterone secretion from the adrenal cortex. It results

in retention of salt and water in the blood. By this way, the blood pressure can be easily

regulated by the aldosterone with homeostasis effect. However, excessive sodium and

water retention will cause edema.

4.6.2. (i)Maintains sodium and water homeostasis

Aldosterone helps regulate the bodys electrolyte balance by stimulating

reabsorption of sodium and water along with the excretion of potassium. It increases the

transport of sodium through the activation and synthesis of epithelial sodium channels in

the kidneys, intestine, sweat and salivary glands. The subsequent increased

concentrations of sodium in the cells activate Na+/K+ ATPase molecules which transport

the sodium back into the bloodstream.

4.6.2 (ii) Regulates acid or base balance

When the level of acidity in the body fluid is too high, hydrogen (H+)ions are

secreted out from the intercalated cells in the collecting duct which is stimulated by

aldosterone together with the reabsorption of sodium and excretion of potassium, into the

urine to be excreted out from the body and thus preventing it form binding with

bicarbonate (HCO3) to form bicarbonic aicd (H2CO3). When the body fluid is too basic,

the bicarbonate ions will be reabsorbed in the kidney to bind with the hydrogen ions to

form bicarbonic acid to restore the acid or base balance of the body.

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5.0 APPLICATIONS AND USES OF STEROIDS

5.1 Gene therapy

Ecdysteroids are use in gene-switch systems as inducers. This means that

ecdysteroids are use for gene therapy. These systems are commonly used in vitro

with cultured cells, which analyse the role of a wide array of genes.

5.2 Treatment for diseases

5.2.1. Anti-inflammatory properties

5.2.1. (i) Ecdysteroids

Ecdysteroids use in wound healing, it had been approved that it can shorten

the duration of skin repair.

5.2.1. (ii) Prednisolone

It is used to treat arthritis, asthma, bronchitis, colitis, certain skin rashes and

allergic or inflammatory conditions of nose and eyes. It can be find in the form of

tablets, capsules, liquids, topical creams and gels, inhalers and eye drops,

injectable and intravenous solutions. Prednisolone is being used in the treatment of

blood cell cancers (leukemias), and lymph gland cancers (lymphomas). It is used as a

hormone replacement for whose adrenal glands are not function well. It is usually

used for joints pain and itchy skin. Prednisolone is used to reduce the level of calcium

in blood and it is used to treat patients who are after having trauma. Prednisone is a

synthetic prednisolone.

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5.2.2. Hormonal control

5.2.2. (i) Estrogen

Premarin is a synthetic estrogen to overcome menopause symptoms such as hot

flashes This estrogen drug is used to promote female gender-specific characteristics in

male-to-female transsexuals. Synthetic estrogen is used as birth-control drug, which

inhibit the production and secretion of gonadotropin-releasing hormone, luteinizing

hormone, and follicle-stimulating hormone.Besides, progestin is synthetic progesterone

to reduced menopause symptoms and promote female gender-specific characteristics.

5.2.2. (ii) Testosterone

Synthetic testosterone is used to treat infertility, testosterone deficiency in men and

symptoms of sexual dysfunction in men and women. It also can use as drugs for female-

to-male transsexuals. It also increase the bone mineral density of testosterone deficiency

patient to prevent bone fractures. It also used to prevent dementia and depression.

Testosterone is being used to treat women with premature ovarian failure, Turner's

syndrome, or HIV infection.

5.2.2. (iii) Others

Other steroids like glucocorticoids (Glaucotin) is use specifically to treat

Glaucoma. It has been used as clinical or non-prescription drugs for improvement in

hyperlipidemia.Sitosterols is one of the phytosterols that used to improve symptom of

benign prostatic hyperplasia. Cardiac glycosides (digitalis) is used to treat congested

heart failure and supraventricular tachysrhythmias (atrial flutter, atrail fibrillation and

paroxysmal supraventricular tachycardia,PSVT).

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5.3 Muscle development for athletes

Figure: The use of anabolic steroids on human.

Ecdysteroids was used to stimulate muscle growth, this led to physical performance

increased without training. For instance, sportsman can perform better than his usual

performances (perform out of his ability) after having this ecdysteroids. It also used as

non-toxic muscle-promoting substances for bodybuilders. Some athletes used synthetic

testosterone as a physical and performance enhancing drug illegally. It used to increase

body mass of organisms. Athletes used anabolic steroids to improve performance. It also

used to treat depression and increase a sense of well-being.

5.4 Hormone replacement therapy

Hormone replacement therapy (HRT) involves the participation of synthetic and natural

female hormones such as estrogen and progesterone. This is to overcome the lack of

natural hormones produced in female. The term estrogen replacement therapy (ERT) is

sometimes used. The administration of estrogen and progestin contribute to relieve the

menopause, osteoporosis, and reduce the risk of heart disease.

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6.0 PROS AND CONS OF STEROIDS

6.1 Advantages of steroids

6.1.1. Role of Steroids to Reduce Inflammation

The primary use of steroids in health care is to reduce inflammation and other disease

symptoms. This is because steroids make the whole immune system become less active

by some mechanism. This is useful and applicable to treat illness where there is an

immune component, for example painful joints and ligaments. Steroids cream are used

extensively in treating eczema, an inflammatory condition of the skin attended with

itching and the exudation of serous matter. The inhaler which is used to treat asthma

contains steroid, it has an important in reducing deaths from asthma.

Steroids are the ultimate anti-inflammatory drugs. They are prescribed or used

only when there is no other way to heal those diseases. The use of steroid in medicine is

limited due to very serious side effects in the body. This is the reason why steroids tend to

used usually in sprays and creams, which ensure a maximum steroid dose where it is

needed, and minimum levels in the blood stream.

6.2 Disadvantages of steroids

6.2.1. Serious Problems due to Steroids

Some people need constant prescription of steroid for medical reasons. Knowing

that we all need immune systems to fight infections and cancers, but this is always

destroyed by steroids. Probably these people are at risk of getting cancer, some of them

may be fatal. We see these patterns in those who receive organ transplants, who often

need huge doses of steroids to stop the body from destroying the donated tissue. Cancers

often develop, which shows us how important our white cells are in keeping us cancer-

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free, and how often all of us develop cancer in our daily lives. Most of us may have two

or three tiny cancers inside us at any time. Taking high dose steroids makes it more likely

one of these will develop rapidly.

People on high dose steroids are immune-deficient in every way so that many

organisms that rarely cause problems can overgrow, totally upsetting the normal balance

of mircobes in the body. An example is candida yeast which can grow rapidly in the

mouth causing painful thrush.

6.2.2. Misuse by Athletes/ Bodybuilders

Steroid is sometimes used illicitly by athletes to increase their strength. Those

athletes and bodybuilders who wish to get superiority over their counterparts have a

tendency of using them. The use of steroids among athletes is legally prohibited. An

athlete who takes steroids hormone before the competition can achieve higher levels of

performance and get an edge on the competition. In the view of moral, this is unfair for

other competitors. However, those who have taken steroid hormone can be clinically

tested. The ratio of using steroids is much higher in the bodybuilders as they have no

obligation to anyone of its use. In fact, anabolic steroids are not to be used without a

doctor's supervision and guidance. It could be fatal and cause certain side effects in the

human body, which begin over several days.

Many bodybuilders find it difficult to decide whether to use the steroids or not

considering its side effects with regard to their health. It is better to take the natural route

of bodybuilding rather than taking the route of using steroids.

The reason of why the steroid is not a good choice for bodybuilders is that as soon as the

bodybuilders leave the intake of steroids, the size of the muscles get reduced. Apart from

this, they also lose strength. It looks similar like someone filling air in a balloon and then

lets the air out of it. The use of steroids may give to instant results but it will get give side

effects over certain of time by endangering the body health.

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6.2.3. Health Hazards

Typical problems you will find in people who abuse anabolic steroids include

liver tumors and cancer, jaundice (yellow skin from liver failure), retention of fluid, high

blood pressure, heart attacks and strokes, increases in LDL (dangerous form of

cholesterol), kidney cancer, acne and trembling.

For men, the side effects include shrinking of the testicles, reduced sperm count,

infertility, baldness, development of breasts, increased risk for prostate cancer. For

women, steroid stimulate the growth of facial hair, male-pattern baldness, changes in or

cessation of the menstrual cycle, enlargement of the clitoris, deepened voice. For

adolescents, growth halted prematurely through premature skeletal maturation and

accelerated puberty changes. This means that adolescents risk remaining short for the

remainder of their lives if they take anabolic steroids before the typical adolescent growth

spurt.

6.2.4. Psychological Changes

Steroid also affects the brain. Scientific research shows that aggression and other

psychiatric side effects may result from abuse of anabolic steroids. Men and women

especially with the use of androgenic steroids, high dosages and long-term consumption,

can develop aggressive behavior.

The advantage of this is that one can train harder and more intensely. The

disadvantage is that some cannot properly cope with this, thus letting their aggressions

out on others. They become easily irritated, impatient, and inclined toward quick temper

and anger outbursts. In extreme cases this can lead to an increase in the use of violence

which has caused the breakup of relationships and marriages.

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Remarkable is that some male athletes using steroids can become depressive. The

cause for this may be the fact that these athletes tend to transform a considerable amount

of the consumed steroids into estrogens. One can explain the mood swings and

depressions with the known fact that the male hypothalamus reacts to the female

hormone estradiol. The supposition that steroids would make athletes psychically

dependent and, after their discontinuance, evoke withdrawal symptoms, is not totally

wrong. Those who press 400 pounds on the bench with the aid of steroids and then, after

discontinuing the substance, press only 360 pounds, then 320 pounds, and after a some

time only 300 pounds, can suffer problems with their ego. Many athletes simply forget

that the performance cannot remain at the same level without steroid use. In the

traditional sense, steroids are not habit forming.

7.0 CONCLUSIONS

Based on the variety of steroid structures we conclude that steroids can potentially

perform essential biological and physiological activity in nature. The subtle differences of

its structural activity relationship will determine the general application and uses of

steroids. It is believed that steroid in conjunction with its unique 4-membered rings

system is capable of contributing to the future research and developments. Modification

of the structures by other chemical residues may help to discover more alternative to

fulfill our daily needs. However, there are limitations of steroid that may influence the

user instead of benefits. Misuses of steroids are prone to sign effect and against the

legality. The instructions of steroids usage should be fully obeyed so that to get rid of the

unnecessary consequences.

We are satisfied with the attendance and contribution of each member of the group

except NIL.

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3076966 steroids and its biological activity

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