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GROWTH
HORMONES
OBJECTIVES.
Thursday, April 26, 2018
■ Structure, synthesis and secretion
■ Regulation
■ Plasma level, binding, metabolism
■ Receptor and mechanism of action
■ Actions of growth hormones
■ Applied.
INTRODUCTION
■ Also called
Somatotrophin
■ Hormone of post natal
growth &
development of adult
size
■ Maintain Lean body
mass and bone mass.
Thursday, April 26, 2018
STRUCTURE,
■ Structure – single
unbranched chain – 191
amino acids
■ Mol wt – 2000
■ Species specificity –
human & monkey growth
hormones have same
biological activity so
therapeutically effective.
Thursday, April 26, 2018
SYNTHESIS
■ By acidophilic cells i,.e
“Somatotrophs”
Thursday, April 26, 2018
SECRETION
■ Release – Pulsatile
fashion.
■
■ by sleep, stress,
hormone related to
puberty, starvation,
exercise, hypoglycemia
by somatostatin,
somatomedins, obesity,
hyperglycemia, &
pregnancy.
Thursday, April 26, 2018
REGULATION
■ Hypothalamic
control
■ Negative feedback
■ Other control
mechanisms
Thursday, April 26, 2018
HYPOTHALAMIC CONTROL
■ Control by 2
hormones
■ Growth hormone
releasing hormone
(GHRH)
■ Growth hormone
inhibiting hormone
(GHIH)
Thursday, April 26, 2018
GROWTH HORMONE
RELEASING HORMONE (GHRH)
■ Polypeptide with 44
amino acids
■ Mechanism Of Action
– through Guanylate
cyclase
Thursday, April 26, 2018
FACTORS STIMULATING GHRH
SECRETION
■ Hypoglycemia – through
glucoreceptors in
Ventromedial nucleus of
hypothalamus (NE)
■ Emotions, exercise &
physical stress – pain ,
trauma, surgery &
inflammation.
Thursday, April 26, 2018
FACTORS STIMULATING GHRH
SECRETION
■ Slow wave phase of sleep
(5HT)
■ Certain amino acids –
arginine after protein
meal
■ Growth hormone
releasing peptide (GHRP)
– Ghrelin from oxyntic
glands of stomach
Thursday, April 26, 2018
GROWTH HORMONE
INHIBITING HORMONE (GHIH)
Thursday, April 26, 2018
■ Somatostatin.
■ Polypeptide with 14 amino acids
■ Factors stimulating GHIH –
■ Hyperglycemia
■ High FFA conc.
NEGATIVE FEEDBACK
■ By GH – by releasing
somatostatin from
hypothalamus.
■ By GHRH - ultra short
feedback loop
■ By Somatomedins – Insulin
like growth factos (IGF)
produced by action of growth
hormones on target tissue.
Thursday, April 26, 2018
OTHER CONTROL
MECHANISMS
■ Thyroxine , cortisol
■ Insulin – represses GH gene
expression.
■ Placental growth hormone &
lactogen
■ Obesity
■ Neurotransmitters – DA, NE,
Ach, 5HT, GABA, hitamine
■ oestradiol
Thursday, April 26, 2018
Thursday, April 26, 2018
PLASMA LEVEL, BINDING,
METABOLISM
■ Basal plasma level –
2-4 ng/ml
■ Diurnal variation –
nocturnal peak 1-2 hr
after deep sleep.(70%)
■ Secretory burst more
in children & with
age.
Thursday, April 26, 2018
VARIATION WITH AGE
■ Increases from birth
to childhood.
■ Children > adults
■ Puberty – Peak
■ Senescence -
Thursday, April 26, 2018
CIRCULATION, HALF LIFE
METABOLISM
Thursday, April 26, 2018
■ Circulation – to Plasma proteins
■ Half life – 0-20 min
■ Daily output – 0.2-1 mg/day.
■ Metabolism – liver,
■ Clearance rate – 350L/day
RECEPTOR AND MECHANISM
OF ACTION
■ Mainly on target
tissue, liver & adipose
tissue.
■ Type – Cytokine
family
■ Parts – extracellular
domain,
transmembrane &
intracellular domain.
Thursday, April 26, 2018
RECEPTOR AND MECHANISM
OF ACTION
■ Stimulate IGF by gene ■ Tyrosine kinase
expression.
Thursday, April 26, 2018
INSULIN LIKE GROWTH
FACTORS
■ Somatomedins
■ Produced in liver &
many target cells.
■ Structure – closely
related to insulin but C
chain not seperated &
got extension of A
chain called
D domain.
Thursday, April 26, 2018
INSULIN LIKE GROWTH
FACTORS
Thursday, April 26, 2018
■
■
■
■
IGF I
Somatomedin C
Secretion – before birth
independent of GH, After
birth stimulated by GH
Receptors similar to
insulin
Major role in skeletal &
cartilage growth.
■
■
■
■
IGF II
Multiplication stimulating
activity.
Secretion independent of
GH.
Receptors are Mannose-6-
phosphate
Major role in fetal growth.
ACTIONS OF GROWTH
HORMONES
■ Growth promoting
actions
■ Metabolic action
■ Lactogenic actions.
Thursday, April 26, 2018
GROWTH PROMOTING
ACTIONS
Thursday, April 26, 2018
■ Promotes Linear growth
■ Bone – stimulate osteoblastic activity converts
cartilage into bone
■ Increases bone mass.
■ Cartilage - stimulate proliferation of chondrocytes
in epiphyseal end plate of long bones.
METABOLIC ACTION
Thursday, April 26, 2018
■ Protein metabolism
■ Fat metabolism
■ Carbohydrate
metabolism.
■ Mineral metabolism.
PROTEIN METABOLISM
POSITIVE NITROGEN BALANCE
■ Anabolic effect.
■ Promotes protein deposition in tissue
■
■
amino acid uptake into cell
protein synthesis by Ribosomes
■ Stimulates Transcription.
Thursday, April 26, 2018
FAT METABOLISM
■ Promotes Lypolysis in
adipose tissue.
■ Fat utilization for
energy.
Thursday, April 26, 2018
CARBOHYDRATE
METABOLISM.
■ Antagonistic to insulin &
produces hyperglycemia.
■ Gluconeogenesis
■ Uptake & utilzation of glucose
by tissue for energy
production.
■ Inhibit Glycolysis
■ Increases Glycogen stores.
■ Use FFA for energy production.
Thursday, April 26, 2018
MINERAL METABOLISM.
■ Promotes bone
mineralization in
growing children
■ Through IGF I causes
positive balance for
calcium, phosphate &
magnesium.
■ Promotes reabsorption
of Ca, P & Na
Thursday, April 26, 2018
LACTOGENIC ACTIONS.
Thursday, April 26, 2018
■ Enhances milk production
■ Acts like Prolactin so called Prolactin like effect
of growth hormone.
APPLIED
■ Hyper secretion
■ Hypo secretion.
Thursday, April 26, 2018
HYPER SECRETION
■ Tumours of
acidophilic cells –
somatotrophs.
■ Gigantism
■ Acromegaly.
Thursday, April 26, 2018
GIGANTISM
■ Hypersecretion of growth
hormone in children before
closure of epiphysis of long
bones.
■ c/f – Tall, large hands & feet,
coarse facial features,
bilateral Gynacomastia, loss
of libido, Impotence,
Hyperglycemia.
Thursday, April 26, 2018
ACROMEGALY.
■ Excess of growth hormones in
adults after fusion of
epiphysis.
■ c/f – Acromegalic face,
Prognathism – Protrusion of
lower jaw, Acral part
abnormalities, Kyphosis,
Excessive internal organ
growth, Increased symp
activity.
Thursday, April 26, 2018
HYPO SECRETION.
Thursday, April 26, 2018
■ Dwarfism – Growth hormone deficiency in early
childhood.
■ Pituitary
■ African pygmies
■ Laron dwarfism
PITUITARY DWARFISM
■ Growth retardation in all
parts proportionately.
■ Short stature
■ Normal mental activity
■ Plumpness, immature
faces, delicate extremity
& when associated with
Gonadotropin deficiency
– no sexual maturity.
Thursday, April 26, 2018
Thursday, April 26, 2018
AFRICAN PYGMIES
■ Lack of Growth
hormone receptors in
tissue.
■ Both GH &
Somatomedins –
normal
■ Plasma IGF-I level fails
to increase.
Thursday, April 26, 2018
LARON DWARFISM
■ Congenital
abnormality of GH
receptors
■ Growth hormone
insensitivity
syndrome.
Thursday, April 26, 2018
Thank you.
Thursday, April 26, 2018

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growthhormone-180426100028.pptx

  • 2. OBJECTIVES. Thursday, April 26, 2018 ■ Structure, synthesis and secretion ■ Regulation ■ Plasma level, binding, metabolism ■ Receptor and mechanism of action ■ Actions of growth hormones ■ Applied.
  • 3. INTRODUCTION ■ Also called Somatotrophin ■ Hormone of post natal growth & development of adult size ■ Maintain Lean body mass and bone mass. Thursday, April 26, 2018
  • 4. STRUCTURE, ■ Structure – single unbranched chain – 191 amino acids ■ Mol wt – 2000 ■ Species specificity – human & monkey growth hormones have same biological activity so therapeutically effective. Thursday, April 26, 2018
  • 5. SYNTHESIS ■ By acidophilic cells i,.e “Somatotrophs” Thursday, April 26, 2018
  • 6. SECRETION ■ Release – Pulsatile fashion. ■ ■ by sleep, stress, hormone related to puberty, starvation, exercise, hypoglycemia by somatostatin, somatomedins, obesity, hyperglycemia, & pregnancy. Thursday, April 26, 2018
  • 7. REGULATION ■ Hypothalamic control ■ Negative feedback ■ Other control mechanisms Thursday, April 26, 2018
  • 8. HYPOTHALAMIC CONTROL ■ Control by 2 hormones ■ Growth hormone releasing hormone (GHRH) ■ Growth hormone inhibiting hormone (GHIH) Thursday, April 26, 2018
  • 9. GROWTH HORMONE RELEASING HORMONE (GHRH) ■ Polypeptide with 44 amino acids ■ Mechanism Of Action – through Guanylate cyclase Thursday, April 26, 2018
  • 10. FACTORS STIMULATING GHRH SECRETION ■ Hypoglycemia – through glucoreceptors in Ventromedial nucleus of hypothalamus (NE) ■ Emotions, exercise & physical stress – pain , trauma, surgery & inflammation. Thursday, April 26, 2018
  • 11. FACTORS STIMULATING GHRH SECRETION ■ Slow wave phase of sleep (5HT) ■ Certain amino acids – arginine after protein meal ■ Growth hormone releasing peptide (GHRP) – Ghrelin from oxyntic glands of stomach Thursday, April 26, 2018
  • 12. GROWTH HORMONE INHIBITING HORMONE (GHIH) Thursday, April 26, 2018 ■ Somatostatin. ■ Polypeptide with 14 amino acids ■ Factors stimulating GHIH – ■ Hyperglycemia ■ High FFA conc.
  • 13. NEGATIVE FEEDBACK ■ By GH – by releasing somatostatin from hypothalamus. ■ By GHRH - ultra short feedback loop ■ By Somatomedins – Insulin like growth factos (IGF) produced by action of growth hormones on target tissue. Thursday, April 26, 2018
  • 14. OTHER CONTROL MECHANISMS ■ Thyroxine , cortisol ■ Insulin – represses GH gene expression. ■ Placental growth hormone & lactogen ■ Obesity ■ Neurotransmitters – DA, NE, Ach, 5HT, GABA, hitamine ■ oestradiol Thursday, April 26, 2018
  • 16. PLASMA LEVEL, BINDING, METABOLISM ■ Basal plasma level – 2-4 ng/ml ■ Diurnal variation – nocturnal peak 1-2 hr after deep sleep.(70%) ■ Secretory burst more in children & with age. Thursday, April 26, 2018
  • 17. VARIATION WITH AGE ■ Increases from birth to childhood. ■ Children > adults ■ Puberty – Peak ■ Senescence - Thursday, April 26, 2018
  • 18. CIRCULATION, HALF LIFE METABOLISM Thursday, April 26, 2018 ■ Circulation – to Plasma proteins ■ Half life – 0-20 min ■ Daily output – 0.2-1 mg/day. ■ Metabolism – liver, ■ Clearance rate – 350L/day
  • 19. RECEPTOR AND MECHANISM OF ACTION ■ Mainly on target tissue, liver & adipose tissue. ■ Type – Cytokine family ■ Parts – extracellular domain, transmembrane & intracellular domain. Thursday, April 26, 2018
  • 20. RECEPTOR AND MECHANISM OF ACTION ■ Stimulate IGF by gene ■ Tyrosine kinase expression. Thursday, April 26, 2018
  • 21. INSULIN LIKE GROWTH FACTORS ■ Somatomedins ■ Produced in liver & many target cells. ■ Structure – closely related to insulin but C chain not seperated & got extension of A chain called D domain. Thursday, April 26, 2018
  • 22. INSULIN LIKE GROWTH FACTORS Thursday, April 26, 2018 ■ ■ ■ ■ IGF I Somatomedin C Secretion – before birth independent of GH, After birth stimulated by GH Receptors similar to insulin Major role in skeletal & cartilage growth. ■ ■ ■ ■ IGF II Multiplication stimulating activity. Secretion independent of GH. Receptors are Mannose-6- phosphate Major role in fetal growth.
  • 23. ACTIONS OF GROWTH HORMONES ■ Growth promoting actions ■ Metabolic action ■ Lactogenic actions. Thursday, April 26, 2018
  • 24. GROWTH PROMOTING ACTIONS Thursday, April 26, 2018 ■ Promotes Linear growth ■ Bone – stimulate osteoblastic activity converts cartilage into bone ■ Increases bone mass. ■ Cartilage - stimulate proliferation of chondrocytes in epiphyseal end plate of long bones.
  • 25. METABOLIC ACTION Thursday, April 26, 2018 ■ Protein metabolism ■ Fat metabolism ■ Carbohydrate metabolism. ■ Mineral metabolism.
  • 26. PROTEIN METABOLISM POSITIVE NITROGEN BALANCE ■ Anabolic effect. ■ Promotes protein deposition in tissue ■ ■ amino acid uptake into cell protein synthesis by Ribosomes ■ Stimulates Transcription. Thursday, April 26, 2018
  • 27. FAT METABOLISM ■ Promotes Lypolysis in adipose tissue. ■ Fat utilization for energy. Thursday, April 26, 2018
  • 28. CARBOHYDRATE METABOLISM. ■ Antagonistic to insulin & produces hyperglycemia. ■ Gluconeogenesis ■ Uptake & utilzation of glucose by tissue for energy production. ■ Inhibit Glycolysis ■ Increases Glycogen stores. ■ Use FFA for energy production. Thursday, April 26, 2018
  • 29. MINERAL METABOLISM. ■ Promotes bone mineralization in growing children ■ Through IGF I causes positive balance for calcium, phosphate & magnesium. ■ Promotes reabsorption of Ca, P & Na Thursday, April 26, 2018
  • 30. LACTOGENIC ACTIONS. Thursday, April 26, 2018 ■ Enhances milk production ■ Acts like Prolactin so called Prolactin like effect of growth hormone.
  • 31. APPLIED ■ Hyper secretion ■ Hypo secretion. Thursday, April 26, 2018
  • 32. HYPER SECRETION ■ Tumours of acidophilic cells – somatotrophs. ■ Gigantism ■ Acromegaly. Thursday, April 26, 2018
  • 33. GIGANTISM ■ Hypersecretion of growth hormone in children before closure of epiphysis of long bones. ■ c/f – Tall, large hands & feet, coarse facial features, bilateral Gynacomastia, loss of libido, Impotence, Hyperglycemia. Thursday, April 26, 2018
  • 34. ACROMEGALY. ■ Excess of growth hormones in adults after fusion of epiphysis. ■ c/f – Acromegalic face, Prognathism – Protrusion of lower jaw, Acral part abnormalities, Kyphosis, Excessive internal organ growth, Increased symp activity. Thursday, April 26, 2018
  • 35. HYPO SECRETION. Thursday, April 26, 2018 ■ Dwarfism – Growth hormone deficiency in early childhood. ■ Pituitary ■ African pygmies ■ Laron dwarfism
  • 36. PITUITARY DWARFISM ■ Growth retardation in all parts proportionately. ■ Short stature ■ Normal mental activity ■ Plumpness, immature faces, delicate extremity & when associated with Gonadotropin deficiency – no sexual maturity. Thursday, April 26, 2018
  • 38. AFRICAN PYGMIES ■ Lack of Growth hormone receptors in tissue. ■ Both GH & Somatomedins – normal ■ Plasma IGF-I level fails to increase. Thursday, April 26, 2018
  • 39. LARON DWARFISM ■ Congenital abnormality of GH receptors ■ Growth hormone insensitivity syndrome. Thursday, April 26, 2018