Steroids Hormones

8/6/2019 Steroids Hormones

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STEROIDS HORMONES

A Steroid Hormone (abbreviated as Sterone) is a steroid that acts as a hormone.

Steroid hormones can be grouped into five groups by the receptors to which they

bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens.

Vitamin D derivatives are a sixth closely related hormone system with homologous

receptors, though technically sterols rather than steroids.

Steroid hormones are crucial substances for the proper function of the body. The

steroid hormones are all derived from Cholesterol and all contain the same

cyclopentanophenanthrene ring.

They mediate a wide variety of vital physiological functions ranging from anti-

inflammatory agents to regulating events during pregnancy. They are synthesized and

secreted into the bloodstream by endocrine glands such as the adrenal cortex and the

gonads (ovary and testis). Steroid hormones are all characterized by the steroid

nucleus which is composed of three six member rings and one five member ring,

ingeniously labeled A, B, C, and D respectively. The steroid nucleus has thefollowing Structure:

The endocrine glands are responsible for the production of steroid hormones, the

adrenal gland, the ovary, and the testies, commonly known as the gonads. Many but

not all steroids are hormones, however, not all steroids are hormones. They are target

organ hormones meaning they exert a direct effect in peripheral tissue. Some

examples of steroid hormones are 1) Estrogens, 2) Androgens (testosterone), 3)

Progesterone, 4) Corticoids {Glucocorticoids and Mineral corticoids}.

Steroid hormones are composed of three six membered rings and one five membered

ring. These organic compounds are easily identified from a visual stand point by their

"steroid nucleus", which is called cyclopentanophenanthrene. This nucleus looks likethis (show transparency), all hormones have an oxygen at C-3 and a varied substituent

at C-17. This substituent varies according to the different kind of steroid hormones at

hand and can be either Alpha or Beta depending on where they are situated below the

plane of the molecule. There are 6-centers of asymmetry; as a result, there are 64

possible compounds (stereoisomers) with this structure. They are located at C-5, C-

10, C-8, C-9, C-14, and C-13. The rings adopt or puckered conformation over the boat

form because its more stable (steric factor).

Steroid hormones are made on a basis of need. Whenever the body needs a certain

process done or needs a certain protein synthesized, the brain releases a signal to

produce a certain type of hormone. The funny thing is that the signals are transmittedthrough intermediary hormones. I would like to touch briefly on steroid hormones

wide variety of uses. Progesterone- Regulates events during pregnancy Corticoids-

Suppress inflammation reactions and regulates mineral and sugar metabolism.

Androgens- Promote male sex development and maintain male sex characteristics.

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Estrogens- Promote female sex development In plants, auxin is an example of a

steroid hormone that regulates longitudinal cell structure so as to allow bending of the

stalk or stem in phototrophic response. Most steroid hormones are neither basic nor

acidic, with estradole being an exception, being slightly acidic due to the phenol

component.

Five classes of Steroid Hormones: 1. ANDROGENS

2. ESTROGENS

3. PROGESTINS

4. MINERALOCORTICOIDS

5. GLUCOCORTICOIDS

Steroid hormones are cholesterol derivatives in animals that are used for a broad

range of signaling mechanisms. Cholesterol is hydroxylated and shortened (removing

the the C6 hydrophobic side chain at position C21) to the C21 intermediates

pregnenolone and progestagen. The latter is a hormone secreted in the uteruscontrolling ovum implantation. It is also the precursor for the male and female sex

hormones androgens (C19) and estrogens (C18), respectively. Other hormones for

both sexes include the mineralcorticoids (e.g. aldosterone; C21) used to control

kidney function (sodium, potassium, proton absorption), and glucocorticoids (e.g.

cortisol C21), which are stress activators of gluconeogenesis, glycogen, fat, and

protein degradation, similar to the peptide hormone glucagon.

One important enzyme type in sterol metabolism are the monooxygenases. They

catalyze an oxidation-reduction step in the presence of molecular oxygen. One oxygen

atom is used for hydroxyl (or epoxide) formation, while the other is reduced to H2O.

Monooxygenases are also known as cytochrome or mixed function oxygenases.The following steroid hormones will be defined according to their origin and their

major effects.

Androgens

Androgen, also called androgenic hormone or testoid, is the generic term for any

natural or synthetic compound, usually a steroid hormone, that stimulates or controls

the development and maintenance of male characteristics in vertebrates by binding to

androgen receptors. This includes the activity of the accessory male sex organs and

development of male secondary sex characteristics.

Androgens were first discovered in 1936. Androgens are also the original anabolic

steroids and the precursor of all estrogens, the female sex hormones. The primary and

most well-known androgen is testosterone.

Androgens originate in the adrenal cortex and gonads and primarily affect maturation

and function of secondary sex organs (male sexual determination).

Physiological Effects

Androgens induce virilization and are responsible for forming the male external

genitalia in the fetus. Their absence or the absence of testosterone receptors results ina female phenotype, despite the presence of a 46 XY karyotype (eg, androgen

insensitivity syndrome). Androgens are also responsible for the development of the

secondary sexual organs and ducts, the seminal vesicles, and the prostate.

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Androgens also are needed for the development of the male reproductive system.

Males that have been castrated prior to adolescence and sexual maturity require

injections of testosterone to develop functioning adult reproductive organs.

Androgens given to normal males tend to increase the size of the reproductive organs.

Women produce about one-twelfth as much androgen as men. Androgens are essential

precursors of estrogens, and no estrogens can be produced without them. Whether

androgens have physiological actions in women is less clear. Some evidence suggeststhat androgens contribute to bone growth and libido. Mild androgen excess in women

results in excess hair growth (hirsutism) that occurs all over the body but is most often

noted on the face. With increasing androgen excess, menstrual periods become

irregular (oligomenorrhea) and eventually cease (amenorrhea), and women are

virilized.

Postnatal females are not as sensitive as the fetus to androgens, which induce the

growth of sexual hair, temporal balding, acne, clitoral growth, sebum production, and

a deepening of the voice.

Oral androgens decrease high-density lipoprotein (HDL) cholesterol and increaselow-density lipoprotein (LDL) cholesterol. With androgen excess, the extent of these

changes is dependent on the level of androgens in the blood.

Androgens have direct effects on different body systems and also act as precursor

hormones for ovarian and extragonadal estrogen synthesis. Androgen receptors are

present in a variety of tissues like skeletal muscles, skin, gastrointestinal tract,

genitourinary tract, bone, brain, cardiovascular system, placenta, and adipose tissues.

Androgen actions are not completely understood in all of these tissues.

Estrogens or Oestrogens

Estrogen or Oestrogen, is a group of hormones that primarily influence the femalereproductive tract in its development, maturation, and function.

There are three major hormonesestradiol, estrone, and estriolamong the

estrogens, and estradiol is the predominant one.

Estrogens originate in the adrenal cortex and gonads and primarily affect maturation

and function of secondary sex organs (female sexual determination).


While oestrogens are present in both men and women, they are usually present at

significantly higher levels in women of reproductive age. They promote the

development of female secondary sexual characteristics, such as breasts, and are also

involved in the thickening of the endometrium and other aspects of regulating the

menstrual cycle. In males, oestrogen regulates certain functions of the reproductive

system important to the maturation of sperm and may be necessary for a healthy

libido.

Furthermore, there are several other structural changes induced by oestrogen in

addition to other functions.

Structural.o Promote formation of female secondary sex characteristics

o Accelerate metabolism

o Reduce muscle mass

o Increase fat stores

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o Stimulate endometrial growth

o Increase uterine growth

o Increase vaginal lubrication

o Thicken the vaginal wall

o Maintenance of vessel and skin

o Reduce bone resorption, increase bone formation

o

Morphic change (endomorphic -> mesomorphic -> ectomorphic) Control Central Nervous System.

Skeletal System.

Protein Synthesis.

o Increase hepatic production of binding proteins

Coagulation

o Increase circulating level of factors 2, 7, 9, 10, plasminogen

o Decrease antithrombin III

o Increase platelet adhesiveness

Lipid

o Increase HDL, triglyceride

o Decrease LDL, fat deposition Fluid Balance

o Salt (sodium) and water retention

o Increase cortisol, SHBG

Gastrointestinal tract

o Reduce bowel motility

o Increase cholesterol in bile

Melanin

o Increase pheomelanin, reduce eumelanin

Cancer

o Support hormone-sensitive breast cancers.

Lung function

o Promotes lung function by supporting alveoli (in rodents but probably

in humans).

Sexual desire is dependent on Androgen levels rather than Estrogen levels.

Progestins

Progestogens are named for their function in maintaining pregnancy (pro-gestational),

although they are also present at other phases of the estrous and menstrual cycles. The

progestogen class of hormones includes all steroids with a pregnane skeleton, that is,both naturally occurring and synthetic ones.

Progestins originate from both ovaries and placenta, and mediate menstrual cycle and

maintain pregnancy.


Within the nervous system, the neuroprotective and promyelinating effects of

progesterone are promising not only for preventing, but also for reversing, age-

dependent changes and dysfunctions. There is indeed strong evidence that the aging

nervous system remains at least to some extent sensitive to these beneficial effects of

progesterone.

Estrogen stimulates cells to grow, which can lead to cancer. Progesterone inhibits the

action of estrogen, hence it is protective against cancer.

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Progesterone prevents lipid peroxidation and confers vascular protection. It has an

antiatherogenic action by preventing the conversion of cholesterol into cholesteryl

ester. It prevents vasoconstriction by increasing levels of nitric oxide (NO), which

causes vasodilation allowing blood vessels to relax, and so widens them allowing

more blood to flow through and it inhibits platelet aggregation.

Progesterone helps with both depression and insomnia as it raises serotonin levels in

the brain. Serotonin is our 'happy' neurotransmitter, it is also the precursor tomelatonin (the 'sleep' hormone).

One of the little known effects of progesterone is that it has a calming effect by

activating the GABA receptor sites. GABA is our most calming, inhibitory

neurotransmitter and effective against some forms of epilepsy.

Progesterone boosts the immune system. It is also neuroprotective and helps stabilize

blood sugar.

Progesterone plays a major role in the body:

It is not a female hormone

It is not a sex hormone, it plays no part in the secondary sexual characteristics

which develop at puberty

It is secreted primarily by the ovaries in women and the testes in men

Smaller amounts are produced by the adrenal glands, the brain and glial cells

(non-neuronal cells that provide support and nutrition)

There are no quantitative differences between men and women (at least

outside the luteal phase).

Here is a more or less comprehensive listing of the effects of progesterone.

The precursor to the sex hormones estrogen and testosterone.

Is essential for implantation and pregnancy maintenance.

Prevents lipid peroxidation.

Acutely inhibits cholesteryl ester formation which is associated with

atherosclerosis.

Confers coronary vascular protection.

Protects against breast, ovarian and endometrial cancer.

Increases relaxation in human placental arteries and veins.

Increases intelligence in utero.

Inhibits the mitogenic action of estrogen on the endometrium and enhancesdifferentiation.

Has an inhibitory effect and reduces epileptiform activity in the brain.

Has immunosuppressive properties.

Simulates leptin secretion.

Sleep improvement.

Influences spermiogenesis, sperm capacitation/acrosome reaction and

testosterone biosynthesis in the Leydig cells in men

Significant reductions in menopausal symptoms

Significant improvement in vasomotor symptoms

Acts indirectly to increase aldosterone by mechanisms similar to sodiumrestriction

Is effective in reducing the risk of spontaneous abortions in high-risk patients

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Prevents recurrent miscarriage and reduces implantation failure in assisted

reproduction cycles

Reduces the frequency of uterine contractions and the rate of preterm delivery

in women at high risk for prematurity

Inhibits in-vitro embryotoxic Th1 cytokine production to trophoblast in

women with recurrent pregnancy loss.

Promotes regeneration and myelination of axons.

Has a neuroprotective and antioxidant effect in injured nervous system

Has multiple effects on glial cells.

It influences growth, differentiation and increases the expression of myelin-

specific proteins in oligodendrocytes, and potentiates the formation of new

myelin sheaths by Schwann cells in vivo.

The loss of progesterone may contribute to the deficits observed after

ovariectomy or the increased risk for Alzheimer's disease seen after the

menopause.

The metabolite allopreganolone potentiates the action of GABA.

It appears to act directly on bone by engaging an osteoblast receptor or

indirectly through competition for a glucocorticoid osteoblast receptor

It increases cell number in human osteoblastic cells.

Induces the increase of the parasiticide activity of the leukocytes involved in

the mechanisms of Trichinella spiralis newborn larvae death.

significantly lower levels of progesterone are found in women with PCO in the

early luteal phase which may contribute to the delay in conception in these

patients.

The abnormal capacity to synthesize progesterone in PCOS may explain the

anovulation and miscarriage that occurs in these patients.

Lower levels of the anxiolytic progesterone metabolite allopregnanolone are

found in the luteal phase of women with PMS. Serum allopregnanolone levels are significantly lower in women experiencing

postpartum "blues".

It is shown to be efficacious when continuation of pregnancy is hampered by

immunological factors, luteinic and neuroendocrine deficiencies and

myometrial hypercontractility, this may explain the reduction in the incidence

of preterm birth in high-risk pregnant women using high-dosage prophylactic

progesterone.

It reduces the frequency of uterine contractions and the rate of preterm

delivery in women at high risk for prematurity.

Evidence suggests that HLA-G plays a critical role in maternal immunetolerance to the fetus, it was found that progesterone has an up-regulatory

effect on HLA-G gene expression in first trimester trophoblasts.

Conservative treatment with high-dose progesterone for endometrial

hyperplasia and well-differentiated early-stage adenocarcinoma followed by

assisted reproductive technologies is an appropriate means for achieving

pregnancy.

In assisted reproduction, luteal support is mandatory and progesterone is the

most widely used hormone, it can be delivered orally, intramuscularly and

vaginally. The oral route is the least efficient but the intramuscular route is as

efficient as the vaginal route; however, the latter is more acceptable, especially

during prolonged treatments, such as oocyte donation and frozen embryotransfer cycles, is used effectively to prevent threatened abortion in the first

trimester.

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Higher serum concentrations of progesterone but not oestradiol, in early

pregnancy were related to lower mean systolic blood pressures in the second

and third trimesters.

A progesterone/testosterone cream was able to help correct the hormonal

imbalance commonly found in men with erectile dysfunction

Used in the treatment of benign prostate hyperplasia (BPH) in men via a

transscrotal delivery system. Used to lower dihydrotestosterone levels in men, the progesterone metabolite

17-0H-progesterone was found to have the highest inhibitory effect on 5-alpha

reductase.

Low allopregnanolone levels in premenopausal women with PTSD (post

traumatic stress disorder) might contribute to an imbalance in inhibitory versus

excitatory neurotransmission, resulting in increased PTSD re-experiencing and

depressive symptoms.

It demonstrates a significant increase of the elastic skin properties, a greater

reduction in wrinkle counts and wrinkle depth around the right eye, a greater

decrease in nasolabial wrinkle depth and a significantly higher increase in skin

firmness in peri- and postmenopausal women. Topically applied progesterone is rapidly absorbed transdermally and its

patterns of distribution and metabolism are comparable to those previously

reported for intravascularly administered progesterone.

The progesterone metabolite allopregnanolone reduces the brain's response to

stress.

Progesterone regulates the secretion of catecholamines during stress, modifies

positively the cardiovascular and catecholamine response to mental stress in

menopausal women.

It reduces programmed cell death and the synthesis of inflammatory factors

that can kill neurons hours to days after traumatic brain injury. As an anti-inflammatory agent progesterone has been shown to reduce the

response of natural killer cells as well as other known initiators of

inflammation.

Systemic injections of the neurosteroid progesterone given after traumatic

brain injury (TBI) have been shown to improve cognitive, sensory and motor

recovery, enhancing both short and long term recovery.

Readily crosses the blood brain barrier (BBB) reducing oedema to barely

measurable levels.

Reduces lipid peroxidation and the generation of isoprostanes, which

contribute to post-injury ischaemic conditions.

Produces metabolites which decrease pro-apoptotic and increase anti-apoptotic

enzymes.

Reduces the expression of pro-inflammatory genes and their protein products.

Reduces the area of necrotic cell death and improve behavioural outcomes.

Protects neurons distal to the site of injury which would normally die after

TBI.

Enhances remyelination in degenerative disorders.

Produces significant sparing of cognitive, sensory and spatial learning

performance after bilateral brain injury.

TBI yielded extremely promising results and found no adverse events

attributable to progesterone. Unlike estrogen which can exacerbate brain injury, especially in animal

models of ischaemic stroke, progesterone can be given to both males and

females without affecting gender and sexual functions.

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Progesterone, unlike the synthetic progesterone medroxyprogesterone acetate

(MPA), cannot increase infectibility to sexually transmitted diseases. MPA

also increases susceptibility to genital herpes (HSV-2) ten times more than

does natural progesterone.

Progesterone brings about relaxation of smooth muscle in the urinary system.

Glucocorticoids

Glucocorticoids originate in the adrenal cortex and affect mainly metabolism in

diverse ways; decrease inflammation and increase resistance to stress.

Mineralocorticoids

Mineralocorticoids originate in adrenal cortex and maintain salt and water balance.

Regulation and ControlHormones are needed throughout the body for various functions, however, just as

important as this function is the regulation and control of these steroids.

Androgens and estrogens play a major role in the development of both sexes

secondary characteristics. Androgens, or testosterone and androsterone give the male

its sex characteristics during puberty and for promoting tissue and muscle growth.

Estrogens, or estrone and estradiol are forms of testosterone synthesized in the

ovaries, which control female secondary characteristics and regulation of the

menstrual cycle. Another sex hormone is needed for preparing the uterus for

implantation of the ovum, this hormone is progesterone

Estrogene and testosterone are very useful steroid hormones, however, excessive

amounts of both can have serious effects. For example; we are aware that estrogen

regulates female characteristics just as testosterone does for males. However, estrogen

is also a crucial risk factor in breast cancer. There is a component known as indole-3-

carbinol (I3C for short) that regulates the production of the malignant estrogen by

altering the process by which the body synthesizes this. I3C causes the body to

produce the benign byproduct instead of the highly estrogenic and potentially

carcinogenic one. I3C is found in cabbage and broccoli, so better eat your vegetables.

Effects Of Steroids Hormones

Steroids exert a wide variety of effects mediated by slow genomic as well as by rapid

nongenomic mechanisms. They bind to nuclear receptors in the cell nucleus for

genomic actions. Membrane-associated steroid receptors activate intracellular

signaling cascades involved in nongenomic actions.

Because steroids and sterols are lipid-soluble, they can diffuse fairly freely from the

blood through the cell membrane and into the cytoplasm of target cells. In the

cytoplasm, the steroid may or may not undergo an enzyme-mediated alteration such

as reduction, hydroxylation, or aromatization. In the cytoplasm, the steroid binds to

the specific receptor, a large metalloprotein. Upon steroid binding, many kinds of

steroid receptor dimerize: Two receptor subunits join together to form one functionalDNA-binding unit that can enter the cell nucleus.

In some of the hormone systems known, the receptor is associated with a heat shock

protein, which is released on the binding of the ligand, the hormone. Once in the

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nucleus, the steroid-receptor ligand complex binds to specific DNA sequences and

induces transcription of its target genes.

Synthesis Of Steroids Hormones

The natural steroid hormones are generally synthesized from cholesterol in the gonads

and adrenal glands. These forms of hormones are lipids. They can pass through the

cell membrane as they are fat-soluble, and then bind to steroid hormone receptors

which may be nuclear or cytosolic depending on the steroid hormone, to bring about

changes within the cell. Steroid hormones are generally carried in the blood bound to

specific carrier proteins such as sex hormone-binding globulin or corticosteroid-

binding globulin. Further conversions and catabolism occurs in the liver, in other

"peripheral" tissues, and in the target tissues.

Synthetic steroids and sterols

A variety of synthetic steroids and sterols have also been contrived. Most are steroids,

but some non-steroidal molecules can interact with the steroid receptors because of a

similarity of shape. Some synthetic steroids are weaker, and some much stronger, than

the natural steroids whose receptors they activate.

Some examples of synthetic steroid hormones:

Glucocorticoids: prednisone, dexamethasone, triamcinolone.

Mineralocorticoid: fludrocortisone.

Vitamin D: dihydrotachysterol.

Androgens: oxandrolone, testosterone, nandrolone (also known as anabolic

steroids).

Estrogens: diethylstilbestrol (DES).

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Progestins: norethindrone, medroxyprogesterone acetate.

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Synthesis Of Androgens

Androsterone C19 H30 O2 m.p. 183

Androsterone isolated from male urine. It behaves as a saturated compound and

forms Mono esters. One Oxygen is present as Oxo Group and other as Hydroxyl

Group.

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Testosterone C19 H28 O2 m.p. 155

Testosterone contain one Hydroxyl Group and an , -unsaturated ketone Group. Itcan be produced commercially by the following method:

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Synthesis Of Oestrogens or Estrogens

Oestrone C18 H22 O2 m.p. 259

Oestrone is isolated from the urine of pregnant woman. After its discovery two other

hormones were isolated: Oestriol [C18 H24 O3] and Oestradiol [C18 H24 O2].Oestrone behaves as a ketone (forms an Oxime etc) and contains one Hydroxyl Group

which is Phenolic, one less Methyl Group, containing one Aromatic Ring.

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Synthesis Of Gestrogens

Progesterone C21 H30 O2 m.p. 128

Progesterone is isolated from the Corpora Lutea of pregnant sows.

There are two Keto Groups and one double bond. On catalytical hydrogenation it

gives Dialcohol (Four Hydrogen atoms are used to convert the two Keto Groups into

Alcoholic Group).

Progestrone can be synthesized from Cholestrol, Stigmasterol, Diosgenin,

Pregnanediol and Ergosterol.

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Steroids Hormones