Physiology of Growth

and Growth Factors

P ROF D R A HMED K AID N A JI A LLOW
SANAA YEMEN
2023
Inteented Learning Outcomes (ILOs)
By the end of this introduction, students should understand
◦ Meaning of growth and development of human body.
◦ Age-periods of growth.
◦ Pattern of growth and development.
◦ Factors affecting growth: Nutritional and Metabolic factors
◦ Environmental factors that affect growth of human body
◦ Hormones that interact with growth
◦ Growth, thyroid hormones and growth
◦ Vit D and PTH and growth
◦ Growth factors (definition, functions, types, characteristics, mechanisms
of action and abnormalities.
◦ Apoptosis and conclusion .
 1
Meaning of growth in the dictionary
The online Oxford English dictionary defines growth as ‘an increase in size and the amount of
something’.
In human body it is a dynamic process with somatic changes in stature, body proportion and
body composition that involves
◦ cell hyperplasia (increase in cell number),
◦ hypertrophy (increase in cell size)
◦ and apoptosis (programmed cell death).

Generally, Human growth is a complex physiological process unique to fetal life, childhood
and adolescent life that is tightly regulated by genetic, hormonal and environmental factors.
A growth factor, is a secreted biologically active molecule that can affect the growth of cells.
This definition has been expanded to include secreted molecules that promote or inhibit mitosi
s or affect cellular differentiation.

Growth-Definition
GROWTH
It is the process of physical maturation
resulting an increase in the size of the body
and various organs.
Multiplication of cells.
An increase in the intracellular substances
It is a quantitative changes of the body.
It is stopped when maturity attened
2
DEVELOPMENT
It is a functional and physiological maturation
of human individual.
It is like myelination of the nervous system and
includes
Psychological, emotional and social changes.
It is a qualitative aspects
It is continued throughout the life
It is a progressive increase in skills and ability
to perform normal functions
 3

Age periods of the growth

1. Fertilization and formation of zygote.
2. Embryonic period: first 8/40 weeks of
intrauterine life.
3. Fetus period: from 8/40 weeks till birth.
4. Infancy: from birth to 2 years.
5. Childhood From 2- 19 yrs
6. Adulthood 19-65 yrs
7. Old age – after 65 yrs
 4

Growth of
Tissue
the human
growth
body

Hyperplasia Tissue
differentiation
Hypertrophy During the
maturation embryonic life
 5

Pattern of growth and development

General- weight and height will increase until 18
years. It is controlled by
◦ gene control,
◦ hormonal,
◦ nutritional and environmental.
◦ Neural – growth of brain and spinal cord; at the end
of 5 years-brain growth=100% but the size of
neurons and dendrite branching and synapses will
continue it development
Lymphoid-organs: tonsils, thymus, spleen, lymph
nodes, and lymphoid tissues of intestine grow
until the end of second decade of human, life see
picture.
Reproductive – gonads and accessory
reproductive organs. Grows at rapid rate around
puberty.
Factors affecting growth 6

Nutritional and Metabolic factors

Balanced diet: like
◦ Proteins, fats, Carbohydrates, vitamins and minerals will play a crucial role in the process of growth
development
◦ Undernutrition and malnutrition in childhood period.
◦ Balance between anabolism and catabolism
◦ Example: Protein anabolism is favored by growth hormone and thyroid hormone and insulin.
◦ Catabolism is favored by glucocorticoids
Environmental factors 7

that affect growth of human body

PRENATAL - FETUS POSTNATAL - NEWBORN

1. Maternal malnutration 1. Nutrition.

2. Maternal infection 2. Childhood illness
3. Hormones-disorder 3. Physical environment
4. Maternal abuse. 4. Psychological environement
5. Miscellaneous. 5. Hormonal influence
Hormal factors 8

that affect growth of human body

Growth hormone:
◦ Secretion – somatotrophs.
◦ Rate of secretion- 1-2mg day and pulsatile in nature.

Clinical implications: the height of the individual during childhood is promoting

the linear growth in the skeleton.
Increase size of the muscle, connective tissue, viscera by promoting hyperplasia
and hypertrophy of cells.
Applied clinical physiology:
◦ GH is inhibited by somatostatin.
◦ GH plus IGF-1 are required for the proper growth
◦ Applied medical physiology: Dwarfism; gigantism, and acromegaly
 Hormones that interact with growth 9

Growth hormone; (Cell membrane receptors) secretes from the pituitary gland and enhances cell division and
growth and development. Abnormalities after birth dwarfism; gigantism and acromegaly.

Thyroid hormone, (Nuclear receptors) important for metabolism (basal metabolic rate) physical, sexual and
mental growth; abnormalities during intrauterine life – creationism; after berth hypo and hyperthyroidism. For
babies born with maternal hypothyroidism treatment can be done in the first 2 years of age. After 2 years it can not
cross the BBB.

Adrenal androgens, (Cytoplasmic receptors) produced by adrenal (cortex) glands DHEA (precursor for
testosterone and estrogens) and androstenedione (they are under the control of ACTH): development in the hair if
increased will lead to hirsutism in female

Sex steroids, (cytoplasmic receptors) like estrogens, progesterone and testosterone that regulate reproduction

glucocorticoids, like cortisol secreted from the suprarenal glands and regulate metabolism.

ghrelin, produced by stomach, hypothalamus, pancreas, and plays a role in regulating appetite, energy
production and stimulates release of growth hormone

leptin and

insulin – (only the lipogenesis hormone) also interact with the growth hormone-insulin-like growth factor-1 axis.
 10

Growth hormone and growth

 Growth hormone (GH) is a pituitary hormone which promots growth of human body during intrauterine
and after berth life.
 Human growth hormone (HGH), also known as somatotropin,
 it is a 191 amino acid single-chain polypeptide produced by somatotropic cells within the anterior
pituitary gland.
 As its name implies, scientists originally found it to be responsible for growth regulation during childhood.
However, research has determined that HGH is also responsible for the regulation of many of the body’s
other basal metabolic functions and operates as an acute phase stress reactant.
 It increases the growth of the body and cell division, increases the body weight and length of the body.
 GH-Receptors are in the cell membrane.
 It is working directly in the skeletal muscle, bones and adippose tissue (lipolysis).
 It is Inhanced ghrelin action.
 It is Inhanced the action of insulin.
 All these actions we will discuss it in the physiology course – Endocrine-glands-physiology.
 11

Growth Hormone - regulation

STIMULATORY INHIBITORY
 Difeciency of energy
o REM sleep
 Hypoglycemia
o Glucose
 Excersice
o Obesity
 Fasting
 Protein meal
o Cortisol
 Glucogon o FFA
 Ghrelin o Aging Gh
 Deep sleep o IGF-1
 Estrogens and androgens o somatostatin
 12

Somatomedins
 Somatomedin – A (IGF2) required during fetal life , secreted
by the liver and its secetion is largely independent of GH
 Somatomedin-B
 Somatomedin-C are not required during fetal life

 In fetus when IGF-2 is over experessed, the growth of organs

is disproportionated
 13

Applied medical physiology of GF

Hyposecretion
Dwarfism – GH deficiency
◦ IGF-1 deficiency
◦ Live-Laron dwarfism – high GH but IGF-1 and IGF-2 are low lack
functional hepatic GH

Hypersecretion of GH
◦ Gigantism
◦ Acromegaly
 Thyroid hormone and growth of nervous 14

system
 They are permissive to GH
 Req. IUL and after birth
 Nervous system – branching of dendrites , synapses
and development of mental activity and physical
activity, myelination, synapses
 Applied clinical physiology Hypothyroidism
 Cretinism
Growth and 15

androgens and estrogens

 The androgens and estrogens are responsible for
growth spurt at puberty
 Testosterone – growth in male
 Estrogen more patent than testosterone for having
action on epiphesal growth plate

 Glucocorticoids – permissive role on GH

 Insulin- lipogenesis stim growth diabetic child dont
grow
 CHO + Proteins+ Insulin= growth
 16

Vit D, PTH and growth

Vit D and PTH stimulate the intake of calcium and direct
action on the mineralization of bones.
Applied physiology:
◦ Rickets in children and osteomalasia in adult
 17

Growth factors
Often, the term growth factor is interchangeably used with the term cytokine.

Growth factors act on the cells of the growing tissues. But cytokines are concerned
with the cells of immune system and hemopoietic cells.
Growth factors has the outer cell-membrane receptors / surface cell
membrane receptors or plasma membrane-bound protein receptors.
Growth factors show tyrosine kinase activity, meaning they put a phosphate
group on a downstream protein tyrosine residue.
"Downstream" here means an event triggered after TGF-beta binding to its
receptor.

Growth factors
Growth factors (GF) are proteins which act as
◦ cell signaling molecules like cytokines
◦ and hormones. GF –stimulate cell-growth and repair,
healing, and development like epidermal growth factor
(EGF) and platelet-derived growth factor (PDGF).
Function of these factors: bind with specific surface
receptors of the target cell and activate
◦ Proliferation: rapid increase in the number of cells or
rapid reproduction of the cells
◦ Differentiation: formation of normal functioning cells in
the human body. Differentiation also reflect to the
processes that make a different tissues and organs.
◦ Maturation of these cells: development of differentiated
cells to perform its function and make a normal
homeostasis with all organs and tissues of the human
body
Cytokines: Group of small proteins which
produces by various cells like immune 18
system to modulate the immune reaction
like:
Interleukins(IL).
IL-1:- stimulate inflamation
IL-2:- promotes T-cells growth and
activation.
IL-6:- regulate inflamation and immune
responses
Tumor Necrosis Factors (TNF) playing
important roles in the process of
inflamation and cell death (apoptosis)
Interferons: antiviral agents ; inhibits
viral replications,
IFN-alpha:- and beta are important in
the defens mechanism against viral
infection.
Chemokines: coordination of immune
response.
 Growth Factor Function
Platelet-derived growth factor – PDGF Group of proteins, secreted by platelets and involve in the blood clotting, wound healings, and
repair as well as cell growth and development
Colony stimulating factors – CSF Group of proteins that regulate the production of none-marrow & immune system
Nerve growth factors – NGF Group of proteins that pay a critical role of neurons (growth, repair and development)
(synaptogenesis)
Neurotropins Group of proteins which are essintial for growth maintenance and plasticity of neurons
Erythropoietin A protein secreted by kidneys and enhances erythropoiesis in th bone-marrow
Thrombopoietin Protein that initiate the cascade blood coagulation
Insulin-like growth factors – IGFs (IGF-1 from Peptide similar to insulin. Mantain the growth over-all the body. Produced by liver, muscle,
other tissue &2 from liver during IU-life) bone, and adipose tissue. It is controlled by growth hormone. IGF-1 working after birth and
IGF-2 during intrauterine life
Epidermal growth factor present in keratinocytes and fibroblasts. It inhibits growth of hair follicles and cancer cells
Basic fibroblast growth factor present in blood vessels. It is concerned with the formation of new blood vessels
Myostatin present in skeletal muscle fibers. It controls skeletal muscle growth
Transforming growth factors (TGF) present in transforming cells (cells undergoing differentiation) and in large quantities in
tumors and cancerous tissue. TGF is of two types.
TGFα secreted in brain, keratinocytes and macrophages. It is concerned with growth of epithelial
cells and wound healing
TGFβ secreted by hepatic cells, T lymphocytes, B lymphocytes, macrophages and mast cells. When
the liver attains the maximum size in adults, it controls liver growth by inhibiting proliferation
of hepatic cells. TGFβ also causes immunosuppression.
 20

Growth factors – characterisics

Some growth factors are small peptides called cytokines.
While all cytokines affect signal transduction pathways, only those cytokines affecting
cell growth/differentiation signaling pathways are considered growth factors.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an example of a
cytokine growth factor since it promotes the production of white blood cells by stem cells.
Examples of protein growth factors are vascular endothelial growth factor (VEGF),
epidermal growth factor (EGF), and platelet-derived growth factor (PDGF).
Growth factor specificity to particular cell types is achievable by the expression of highly
specific cell surface receptors. For example, some growth factors act only on
hematopoietic cells, which are cells derived from bone marrow.
 21

Growth factors – characterisics continue

 Some growth factors like lipid-soluble steroid hormones, do not have a surface
receptor and can directly pass through the cell's plasma membrane, bind to an
intracellular protein receptor, or nuclear receptors, and then transmit a growth
signal.
 Glands produce all hormones and secrete them into the circulatory system.
 Estrogens, androgens, and progestogens are examples of steroid hormones that
are growth factors. Not all hormones are growth factors, only those affecting
cell growth/differentiation.
 Even simple small molecules such as nitric oxide or reactive oxygen species
(ROS) can act as growth factors.
 22

Apoptosis-programing cell death

 Death receptor ligands are the substances which bind with specific cell
membrane receptors and initiate the process of apoptosis. The common
death-receptor ligands are tumor necrosis factors.
 It can be programing
 and non-programing cell death.
 During the pathological disorders, it can cause non-programing cell death.
 Normal programing cell death appears during normal physiological condition
like red blood cells are dying after 100-120 days stomach mucosal cells after
6 hours to 2 days are replaced.
 Conclusion 23
Generally, Human growth is a complex physiological process unique to fetal life and childhood and
adolescent life that is tightly regulated by genetic, hormonal and environmental factors.
A growth factor, as initially defined, is a secreted biologically active molecule that can affect the growth of cells
. This definition has been expanded to include secreted molecules that promote or inhibit mitosis or affect cellul
ar differentiation.
They have a surface cell membrane receptors.
They has a kinase phosphatase activity.
All steroid hormones are working as growth factor hormones and has lipid-soluble characteristics.
Growth factors (GF) are proteins which act as cell signaling molecules like cytokines
◦ and hormones. GF –stimulate cell-growth and repair, healing, and development like epidermal growth factor (EGF) and platelet-
derived growth factor (PDGF).

Function of growth factors: bind with specific surface receptors of the target cell and activate
◦ Proliferation: rapid increase in the number of cells or rapid reproduction of the cells
◦ Differentiation: formation of normal functioning cells in the human body. Differentiation also reflect to the processes that make a
different tissues and organs.
◦ Maturation of these cells: development of differentiated cells to perform its function and make a normal homeostasis with all organs
and tissues of the human body.
◦ Many physiological activity can be deteriorate due to problems in the GH and Gf biosynthesis and action like dwarfism and
creationism.
Thank you for your attention and
Does you have any question?