BIOLOGY INVESTIGATORY PROJECT

TOPIC:GROWTH HORMONE

SUBMITTED BY:-ANUSHA MELLAPALAYAM 11A

S.NO TOPIC PAGE

1 Introduction to growth hormone 1

2 History of growth hormone 2&3

3 Structure of growth hormone 4

4 Function of growth hormone 5

5 Disorder of growth hormone 6

(acromegaly)

6 Causes of acromegaly 7

7 Symptoms of acromegaly 8

8 Test of acromegaly 9

9 Treatment of acromegaly 10

10 Gigantism introduction 11

11 Causes of Gigantism 12

12 Symptoms of Gigantism 13

13 Test of Gigantism 14

14 Treatment of Gigantism 15

15 Dwarfism introduction 16

16 Causes of Dwarfism 17

17 Symptoms of Dwarfism 18

18 Test of Dwarfism 19
19 Treatment of Dwarfism 20

20 Conclusion 21

21 Bibliography 22
 GROWTH
HORMONE
:
Growth hormone also
known as
somatotropin or as
human growth
hormone hormone
also known as
somatotropin or as
human growth
hormone [HGH] in its human form, is a peptide hormone that stimulates growth I cell
reproduction and cell regeneration in human development. It is a type of mitogen
which is specific in its human form, is a peptide hormone that stimulates growth I cell
reproduction and cell regeneration in human development. It is a type of mitogen
which is specific only to certain kind of cells. Growth hormone is a 191-amino acid,
Single- chain polypeptide that is synthesized, stored and secreted by somatotropin
cell within the lateral wing of the anterior pituitary gland.

Since the recognition of its multiple and complex effects in the early 1960s, the
physiology and regulation of GH has become a major area of research interest in the
field of endocrinology. In adulthood, its main role is to regulate the metabolism.
Pituitary synthesis and secretion of GH is stimulated by episodic hypothalamic
secretion of GH releasing factor and inhibited by somatostatin. Insulin-like Growth
Factor I (IGF-I) inhibits GH secretion by a negative loop at both hypothalamic and
pituitary levels. In addition, age, gender, pubertal status, food, exercise, fasting,
sleep and body composition play important regulatory roles.

HGH has numerous roles throughout life, from growth itself (including the turnover of
muscle, bone and collagen) to the regulation of particular aspects of metabolic
function, for example increased fat metabolism and the maintenance of a healthier
body composition in later life.HGH is secreted in a pulsatory way, roughly following a
circadian rhythm. Various physiological stimuli can cause HGH secretion, with the
most influential non-pharmacological stimuli being sleep and exercise.
Growth hormone was discovered by Choh Hao Li in the year 1955.He and Herbert
Evan together discovered the GH. Li began to develop methods for isolating the
anterior pituitary hormones in pure form. Li was either the first or among the first to
isolate and identify the anterior pituitary hormones. The initial breakthrough came in
1940 when he isolated luteinizing hormone. ACTH was the first hormone to be
chemically identified and partially synthesized. It took 32 years of research for Li to
synthesize the human growth hormone. The identification, purification and later
synthesis of human growth hormone and the identification of beta-endorphin were his
two most widely recognized achievements. His last accomplishment was the
identification and purification of insulin-like growth factor I.

The efforts to acquire pituitary GH for the treatment of GH-deficient children started in
the mid-1940s. Initial work was on subprimates for nearly a decade. These efforts led
to the purification of bovine GH by Li and Evans at the University of California,
Berkeley, and Fishman at Yale. And porcine GH was purified by Raben and
Westermeyer, at Tufts. But none of these preparations showed a significant
biochemical or metabolic activity because the effects of GH is species specific.

Growth hormone (GH) first was isolated from the human pituitary gland in 1956, by
both Li and Papkoff, in California, and Raben, in Massachusetts, but its biochemical
structure was not elucidated until 1972. In 1958, Raben reported the results of the first
trial to show the effects of human GH on growth. By 1960 it was clear that GH-deficient
children would benefit from pituitary GH. In 1960, National Pituitary Agency (NPA) was
formed to further the goals of coordinating pituitary collection and extraction to support
both basic and clinical research. Between 1963 and 1985 the NPA supervised almost
all of the GH treatment in the United States. And during this period about 7700 children
in the United States and 27,000 children worldwide were given GH extracted from
human pituitary glands to treat severe Growth hormone deficiency (GHD).[3,4]

By 1985, pituitary GH was in use for nearly 30 years in the United States and Canada,
either for research purpose or therapeutically. In 1985, US Food and Drug
Administration (US FDA) received reports of four young adults in the United States
with the fatal, slow viral (prion-mediated) Creuzfeldt Jacob Disease (CJD), who had
been treated with GH from the NPA in the 1960s. The connection was recognized on
reviewing data within a few months by FDA and NIH. On April 19, 1985, distribution of
pituitary GH was suspended and use of human pituitary GH rapidly ceased. And an
exciting and important era in pediatric endocrinology came to an abrupt finish.
The major isoform of the human growth hormone is protein of 191 amino acids and a
molecular weight of 22,124 daltons. The structure includes four helices necessary for
functional interaction with GH receptor. It appear that in structure, GH is evolutionarily
homologous to proclaim and chorionic Somatomammotropin. Despite marked structural
similarities between growth hormone from different species, only human and Old World
monkey growth hormones have significant effects on the human

Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In
particular, a variant of approximately 20 kDa originated by an alternative splicing is present
in a rather constant 1:9 ratio, while recently an additional variant of ~ 23-24 kDa has also
been reported in post-exercise states at higher proportions. This variant has not been
identified, but it has been suggested to coincide with a 22 kDa glycosylated variant of 23 kDa
identified in the pituitary gland. Furthermore, these variants circulate partially bound to a
protein (growth hormone-binding protein, GHBP), which is the truncated part of the growth
hormone receptor, and an acid-labile subunit (ALS).
Growth hormone [GH] has many function :

• For growth GH promotes growth in almost every tissue and organ in

the body , especially in bones and cartilage during puberty.
• For development of bones and muscles GH plays an important role.
• For metabolic effects as GH increases the production of insulin-like
growth factor-1(IGF-1), which promotes growth in every cell of body.
• For maintain the body structure GH plays an important role
• GH conserves glucose for glucose-dependent tissues, such as the
brain.
• Ensures the balance of body fluids and maintains normal body
composition of fats , water and blood.
• Controls glucose synthesis, uptake by cells and protein, lipid
metabolism.
• Bolsters energy levels and improves productivity , overall quality of life .
• Enhances brain health cognitive functions and heart wellness.
 DISORDERS

Acromegaly Gigantism Dwarfism

1. ACROMEGALY:-
Acromegaly is a hormonal disorder that develops when your pituitary gland
produces too much growth hormone during adulthood. When you have too
much growth hormone, your bones increase in size. In childhood, this leads to
increased height and is called gigantism. But in adulthood, a change in height
doesn't occur. Instead, the increase in bone size is limited to the bones of
your hands, feet and face, and is called acromegaly.
Because acromegaly is uncommon and the physical changes occur slowly
over many years, the condition sometimes takes a long time to recognize.
Untreated, high levels of growth hormone can affect other parts of the body, in
addition to your bones. This can lead to serious sometimes even life-
threatening health problems. But treatment can reduce your risk of
complications and significantly improve your symptoms, including the
enlargement of your features. Acromegaly is a rare disorder. Approximately 3
to 14 of every 100,000 people have been diagnosed with this kind of
disorder.
Acromegaly is a rare but serious medical condition that happens when you
have high levels of growth hormone (GH) in your body. Your pituitary
gland normally produces GH, but tumors on your pituitary or in other parts of
your body produce excess GH in acromegaly.
Your pituitary gland is a small, pea-sized endocrine gland located at the base
of your brain below your hypothalamus. Your pituitary gland releases eight
important hormones, including GH.
Growth hormone, also known as human growth hormone (hGH) and
somatotropin, is a natural hormone that acts on many parts of the body to
promote growth in children. Once the growth plates (epiphyses) in your bones
have fused, GH no longer increases height, but your body still needs GH.
After you’ve finished growing, GH helps to maintain normal bone, cartilage
and organ structure and metabolism, including helping to keep your blood
glucose (sugar) levels within a healthy range.
If you have too much GH in your body as an adult, it can result in irregularly-
shaped bones, increased organ size, elevated blood sugar levels
(hyperglycemia) and other symptoms.
Acromegaly can develop at any age after puberty, but healthcare providers
most often diagnose it during the fourth and fifth decades of life (middle age).
Acromegaly occurs when the pituitary gland produces too much growth hormone
(GH) over a long period of time.

The pituitary gland is a small gland at the base of your brain, behind the bridge of
your nose. It produces GH and a number of other hormones. GH plays an important
role in managing your physical growth.

When the pituitary gland releases GH into your bloodstream, it triggers your liver to
produce a hormone called insulin-like growth factor-1 (IGF-1) sometimes also
called insulin-like growth factor-I, or IGF-I. IGF-1 is what causes your bones and
other tissues to grow. Too much GH leads to too much IGF-1, which can cause
acromegaly signs, symptoms and complications.

In adults, a tumor is the most common cause of too much GH production:

• Pituitary tumors. Most acromegaly cases are caused by a noncancerous

(benign) tumor (adenoma) of the pituitary gland. The tumor produces
excessive amounts of growth hormone, causing many of the signs and
symptoms of acromegaly. Some of the symptoms of acromegaly, such as
headaches and impaired vision, are due to the tumor pressing on nearby
brain tissues.
• Nonpituitary tumors. In a few people with acromegaly, tumors in other parts
of the body, such as the lungs or pancreas, cause the disorder. Sometimes,
these tumors secrete GH. In other cases, the tumors produce a hormone
called growth hormone-releasing hormone (GH-RH), which signals the
pituitary gland to make more GH.
A common sign of acromegaly is enlarged hands and feet. For example, you may
notice that you aren't able to put on rings that used to fit, and that your shoe size has
progressively increased. Acromegaly may also cause gradual changes in your face's
shape, such as a protruding lower jaw and brow bone, an enlarged nose, thickened
lips, and wider spacing between your teeth .Because acromegaly tends to progress
slowly, early signs may not be obvious for years. Sometimes, people notice the
physical changes only by comparing old photos with newer ones.

Symptoms tends to vary from person to person but most common symptoms are:

• Enlarged hand and feet.

• Enlarged facial features, which includes the facial bones, lips ,nose and
tongue.
• Coarse, oily, thickened skin.
• Small outgrowth Oski tissue.
• Excessive sweating and body odour.

• Fatigue and joint or muscle weakness.

• Pain and limited joint mobility.
• A deepened, husky voice due to enlarged vocal cords and sinuses.
• Severe snoring due to obstruction of the upper airway.
• Vision problems.
• Headaches, which may be persistent or severe.
• Menstrual cycle irregularities in women.
• Erectile dysfunction in men.
• Loss of interest in sex.
If you’ve been diagnosed with acromegaly, your provider may order additional tests
to see if the condition has affected other parts of your body. These tests may include:

• An echocardiogram to check for heart issues.

• Sleep study tests to check for sleep apnea.

• A colonoscopy to assess the health of your colon.

• X-rays or a DEXA (DXA) scan to check bone health.

BLOOD TEST:

• Elevated Growth Hormone(GH) levels

• Elevated serum insulin like growth factor.

ORAL GLUCOSE TOLERANCE TEST:

• Ingestion of 75g of sugar causes GH reduction.
• Normal patient GH reduction occurs but for Acromegaly GH reduction
does not occur.
The most common treatments for acromegaly are surgery, medication and radiation
therapy.
Surgery for acromegaly

In many cases, surgery greatly improves acromegaly symptoms or corrects the

condition entirely. Surgeons most often use a type of surgery called
transsphenoidal surgery, which involves going through your nose and sphenoid
sinus, a hollow space in your skull behind the nasal passages and below your brain,
to perform surgery.
The specifics of the surgery will depend on the size and location of the tumor. The
goal of surgery is to remove all of a tumor that is causing excess growth hormone
production. If your surgeon removes enough of the tumor, you may not need further
treatment. If your surgeon can remove only a part of a tumor, you may need
medication or radiation therapy to manage your symptoms and reduce the
production of growth hormone.

Medications for acromegaly

Your healthcare provider may prescribe one medication or a combination of

medications. Medications work in different ways to normalize your body’s growth
hormone levels and improve your symptoms. In some cases, a person may take
medication until the tumor has shrunk. This can allow a surgeon to then safely
remove it. Other people may need to take medication long-term to effectively
manage growth hormone levels and symptoms.
 2.GIGANTISM:-
Gigantism also called
as pediatric
acromegaly is a rare
condition that causes
abnormal growth in
children. This change is
most notable in terms of
height, but girth is
affected as well. It
occurs when your
child’s pituitary
gland makes too much
growth hormone, which
is also known as somatotropin. Adolescent has high levels of growth hormone
(GH) in their body, which causes them to grow very tall. The pituitary
gland normally produces GH, but a tumor on their pituitary can produce
excess GH in gigantism.
Your pituitary gland is a small, pea-sized endocrine gland located at the base
of your brain below your hypothalamus. Your pituitary gland releases eight
important hormones, including GH.
Growth hormone, also known as human growth hormone (hGH) and
somatotropin, is a natural hormone that acts on many parts of the body to
promote growth in children. Once the growth plates (epiphyses) in your bones
have fused, GH no longer increases height. Instead, it helps to maintain
normal bone, cartilage and organ structure and metabolism. GH is closely
connected to insulin-like growth factor 1 (IGF1), a hormone
your liver releases. These hormones work together to carry out growth and
metabolism functions.
In gigantism, the excessive amount of growth hormone (GH) accelerates the
growth of muscle, bones and connective tissue. This leads to an abnormally
increased height as well as several soft tissue changes. When left untreated
or unmanaged, some people with gigantism have grown over 8 feet tall. n
children, gigantism occurs when they experience excess GH before the
growth plates in their bones fuse (before the end of puberty).
Once your growth plates have fused, excess GH causes acromegaly. In this
case, you don’t grow in height, but the excess GH affects your bones’ shape
and your organ size as well as other health factors.
.The most common cause of gigantism is a benign (noncancerous) tumor on your
child’s pituitary gland (a pituitary adenoma) that releases excess growth hormone
(GH). Children with gigantism almost always have large pituitary tumors called
macroadenomas (a pituitary adenoma that’s 10 millimeters in diameter or larger) at
diagnosis. Gigantism can also be caused by pituitary hyperplasia, which is when
your pituitary gland becomes enlarged.
Many children with gigantism have a genetic mutation that causes the pituitary tumor
to form. The most common genetic mutations associated with gigantism are AIP
gene mutations or deletions, making up approximately 29% of the population of
people with gigantism .Gigantism can occur as a part of several rare genetic
disorders that lead to an increased risk of developing GH-secreting pituitary tumors,
including:

• Carney complex: This is a genetic condition that affects skin color

(pigmentation) and causes benign tumors of your skin, heart and endocrine
system. GH-secreting pituitary adenomas occur in about 10% to 13% of
Carney complex cases and usually have a slow progression.

• Multiple endocrine neoplasias (MEN): These are genetic conditions in

which one or more of your endocrine glands are overactive and/or form a
tumor, which can include a GH-secreting pituitary tumor.

• Neurofibromatosis: This is a condition that’s a part of a group of genetic

conditions known as neurocutaneous disorders that affect your skin
and nervous system. These types of disorders are caused by abnormal
increases in cell growth. This results in the formation of tumors all over your
body, which can include a GH-secreting tumor.
 .

Excessive amounts of growth hormone (GH) cause the signs and symptoms of
gigantism. Children with gigantism can also develop certain symptoms as their
pituitary tumor applies pressure to their nearby brain and nerve tissues. The main
sign of gigantism is excessive growth. Children with gigantism grow rapidly in height.
Aside from being very tall/large for their age, physical characteristics of gigantism
include:

• Very prominent forehead and a prominent jaw.

• Gaps between their teeth.
• Thickening of their facial features.
• Large hands and feet with thick fingers and toes.
• Enlargement of internal organs, especially your child’s heart.
• Excessive sweating (hyperhidrosis).
• Double vision or difficulty with side (peripheral) vision.
• Headaches.
• Joint pain.
• Delayed puberty.
• Irregular menstruation (periods).
• Sleeping problems, such as sleep apnea.
• Muscle weakness.
• a very large appetite.
• Release of breast milk.
Tests to diagnose gigantism include:
• Growth hormone and IGF-1 (insulin-like growth factor 1) blood tests:
These tests measure different hormone levels in your child’s blood from a
sample taken from their vein. Higher than normal levels may indicate
gigantism.
• Glucose tolerance test: This test can assess whether your child’s growth
hormone levels react to glucose (sugar) the way they should. For this test, a
provider will draw blood samples from your child’s vein at different intervals
after your child drinks a glucose (sugar) solution.
• Imaging tests: If blood tests confirm that your child has gigantism, their
provider will probably recommend an MRI (magnetic resonance imaging) scan
or CT (computed tomography) scan, which can clearly show the size and
location of a pituitary tumor and help determine the proper treatments.
These tests may include:

• An echocardiogram to check for heart issues.

• Sleep study tests to check for sleep apnea.

• X-rays or a DEXA (DXA) scan to check bone health.
The goals of treating gigantism include:
• Safely regulating growth hormone (GH) and insulin-like growth factor 1 (IGF1)
levels.

• Managing pituitary tumor growth.

• Reducing the effects of the pituitary tumor on nearby structures, such as brain
tissue and the optic nerve.
• Treating or reducing the effects of GH on other body systems.

Healthcare providers typically use a combination of treatments, specifically surgery

and radiation therapy, for gigantism. Medications are available and effective in
treating acromegaly (excess GH in adults) but the effects of these drugs on children
haven’t been adequately studied. Medication for gigantism are Carbergoline and
bromocriptine(parlodel).
Surgery for gigantism

Surgery is the most common treatment option for gigantism. The goal is to remove or
reduce the size of the pituitary tumor. Since the pituitary tumors that cause gigantism
are often large, children with gigantism may need multiple surgeries to remove the
tumor and effectively regulate GH levels.
 3.DWARFISM:-
Dwarfism is short stature that results from a
genetic or medical condition. Stature is the
height of a person in a standing position.
Dwarfism generally is defined as an adult
height of 4 feet, 10 inches (147 cm) or less. The
average adult height among people with
dwarfism is 4 feet, 1 inch (125 cm) for women
and 4 feet, 4 inches (132 cm) for men.
Dwarfism has many different forms. These
conditions can affect different parts of
the musculoskeletal system including the
growth of the arms, legs, abdomen and/or
head. Dwarfism (skeletal dysplasia) is a rare
condition. The most common type of dwarfism
is achondroplasia, which affects 1 in 15,000 to 40,000 people. Many types of
dwarfism are genetic, which means you can inherit the condition from your parents
and other forms occur randomly through DNA changes.

The two main categories of dwarfism are:

DWARFISM

DISPROPORTIONATE

PROPORTIONATE

Disproportionate dwarfism: is characterized by an average-size torso and shorter

arms and legs or a shortened trunk with longer limbs.

proportionate dwarfism: the body parts are in proportion but shortened.

The most common type of dwarfism are:

TYPES OF
DWARFISM

Achondroplastic Hypochondroplasia

Pituitary Primordial Thanatophoric

dysplasia

• Achondroplastic dwarfism: The most common form of dwarfism is

characterized by short limbs and a prominent forehead.
• Hypochondroplasia dwarfism: A mild type of short-limbed dwarfism with
characteristics not noticeable during infancy.
• Pituitary dwarfism: Dwarfism caused by a growth hormone deficiency.

• Primordial dwarfism: A form of dwarfism where a small body size occurs

during all stages of life, even before birth.
• Thanatophoric dysplasia: A less common, very severe form of dwarfism that
causes very short limbs along with a narrow chest. It usually causes infants to
die shortly after birth due to breathing difficulties.
Several potential causes lead to a dwarfism (skeletal dysplasia) diagnosis. A change
to a person’s DNA causes most cases of dwarfism, while several types have an
unknown cause.
Causes of dwarfism include:

• Familial: If parents and other family members are short, it can be normal for
their child to be short.

• Genetic mutation: Changes to a person’s DNA.

• Growth hormone deficiency: The brain doesn’t make enough of the

hormone that causes bones to grow.

• Late bloomer (constitutional delay): Some children are short earlier in

childhood because they’re programmed to grow later than their peers. There’s
sometimes a family history of a similar pattern of growth.
• Malnutrition: Not having adequate nutrition can affect a child’s ability to grow.

• Small for gestational age: Most babies that are born small will catch up with
their growth within the first two to three years of life, but 10% don’t.
Symptoms of disproportionate dwarfism may include:
• Adults typically are about 4 feet tall

• Average-size torso and very short limbs, especially in the upper halves of
arms and legs
• Short fingers

• Wide spaces between the middle and ring fingers

• Limited elbow mobility

• Disproportionately large head

• Prominent forehead

• Flattened bridge of the nose

• Bowing of legs that progressively worsens over time

• Swaying of the back that progressively worsens over time

• Short neck, arms, and legs, but average-size hands and feet

Symptoms of proportionate dwarfism include a smaller head, arms, and legs. But all
are in proportion with each other. Organ systems may be smaller too.

signs of proportionate dwarfism in children are:

• Slower growth rate than expected for their age

• Height lower than the third percentile on standard charts for age

• Delayed or no sexual development during the teen years

 Genetic tests

Imaging
technology

Hormone
tests

Genetic tests:-

• Genetic tests are available for many genetic causes of dwarfism-related

conditions.

• .This test could help manage the condition and aid in family planning.

• For example, if your doctor thinks your daughter may have Turner syndrome,
a special lab test may be done that looks at the X chromosomes in blood
cells.

Imaging technology:-

• Doing imaging studies, such as X-rays, because certain differences in the

skull and skeleton can indicate which condition your child may have.
• Various imaging devices also may reveal delayed maturation of bones, as is
the case when growth hormone levels are low.
• An MRI scan may show if the pituitary gland or hypothalamus is not typical..
Hormone tests:-
• Tests that measure levels of growth hormone or other hormones that are
critical for childhood growth and development.
Most dwarfism treatments don't increase stature, but they may correct or ease
problems caused by complications.

Medication:-

vosoritide, known by the brand name Voxzogo, to improve growth in children who
have the most common type of dwarfism.

Given as a shot, this medicine is for children 5 years of age and older who have
achondroplasia and open growth plates so they can still grow.

Therapy:-

For people with dwarfism due to low levels of growth hormones, treatment with shots
of a synthetic version of the hormone may increase final height.

In most cases, children receive daily shots for several years until they reach a
maximum adult height — often within the average adult range for their families.

Treatment may continue throughout the teen years and early adulthood to achieve
development. Some people may need lifelong therapy.
Growth hormone is essential for growth, but also modulates protein, lipid, and
carbohydrate metabolism. There is clear evidence that GH excess is associated with
reduced survival, and suggestions that GH deficiency may play a vital part in the
increased mortality seen in patients with hypopituitarism. growth hormone also
increases protein synthesis, gene transcription, and the size and mitosis of somatic
cells. It decreases glucose uptake and utilization and promotes differentiation. Use of
recombinant GH to treat such disorder has many known side effect thus not advised
to take until prescription is provided. GH is a complex hormone that plays important
role in growth and metabolism of protein, carbohydrates and fat. Thus GH plays an
important role in human beings.