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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 the
following 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 like
this (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 it’s 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 transmitted
through 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 uterus
controlling 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 in
a 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 suggests
that 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 increase
low-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 female

reproductive tract in its development, maturation, and function.
There are three major hormones—estradiol, estrone, and estriol—among 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).

Physiological Effects

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.

Physiological Effects

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 to
melatonin (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 enhances
differentiation.
 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 sodium
restriction
 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 immune
tolerance 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 embryo
transfer 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 Control

Hormones 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 functional
DNA-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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with enzymes and intermediates)

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 α, β-unsaturated ketone Group. It

can 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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