GROWTH HORMONES

DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
GROWTH
HORMONES

OBJECTIVES.
 Structure, synthesis and secretion
 Regulation
 Plasma level, binding, metabolism
 Receptor and mechanism of action
 Actions of growth hormones
 Applied.
Thursday, April 26, 2018

INTRODUCTION
 Also called
Somatotrophin
 Hormone of post natal
growth &
development of adult
size
 Maintain Lean body
mass and bone mass.

STRUCTURE,
 Structure – single
unbranched chain – 191
amino acids
 Mol wt – 2000
 Species specificity –
human & monkey growth
hormones have same
biological activity so
therapeutically effective.

SYNTHESIS
 By acidophilic cells i,.e
“Somatotrophs”

SECRETION
 Release – Pulsatile
fashion.
 by sleep, stress,
hormone related to
puberty, starvation,
exercise, hypoglycemia
 by somatostatin,
somatomedins, obesity,
hyperglycemia, &
pregnancy.

REGULATION
 Hypothalamic
control
 Negative feedback
 Other control
mechanisms

HYPOTHALAMIC CONTROL
 Control by 2
hormones
 Growth hormone
releasing hormone
(GHRH)
 Growth hormone
inhibiting hormone
(GHIH)

GROWTH HORMONE
RELEASING HORMONE (GHRH)
 Polypeptide with 44
amino acids
 Mechanism Of Action
– through Guanylate
cyclase

FACTORS STIMULATING GHRH
SECRETION
 Hypoglycemia – through
glucoreceptors in
Ventromedial nucleus of
hypothalamus (NE)
 Emotions, exercise &
physical stress – pain ,
trauma, surgery &
inflammation.

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

GROWTH HORMONE
INHIBITING HORMONE (GHIH)
 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.

OTHER CONTROL
MECHANISMS
 Thyroxine , cortisol
 Insulin – represses GH gene
expression.
 Placental growth hormone &
lactogen
 Obesity
 Neurotransmitters – DA, NE,
Ach, 5HT, GABA, hitamine
 oestradiol

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.

VARIATION WITH AGE
 Increases from birth
to childhood.
 Children > adults
 Puberty – Peak
 Senescence -

CIRCULATION, HALF LIFE
METABOLISM
 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.

RECEPTOR AND MECHANISM
OF ACTION
 Stimulate IGF by gene
expression.
 Tyrosine kinase

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.

INSULIN LIKE GROWTH
FACTORS
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.

GROWTH PROMOTING
ACTIONS
 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
 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.

FAT METABOLISM
 Promotes Lypolysis in
adipose tissue.
 Fat utilization for
energy.

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.

MINERAL METABOLISM.
 Promotes bone
mineralization in
growing children
 Through IGF I causes
positive balance for
calcium, phosphate &
magnesium.
 Promotes reabsorption
of Ca, P & Na

LACTOGENIC ACTIONS.
 Enhances milk production
 Acts like Prolactin so called Prolactin like effect
of growth hormone.

APPLIED
 Hyper secretion
 Hypo secretion.

HYPER SECRETION
 Tumours of
acidophilic cells –
somatotrophs.
 Gigantism
 Acromegaly.

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.

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.

HYPO SECRETION.
 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.

AFRICAN PYGMIES
 Lack of Growth
hormone receptors in
tissue.
 Both GH &
Somatomedins –
normal
 Plasma IGF-I level fails
to increase.

LARON DWARFISM
 Congenital
abnormality of GH
receptors
 Growth hormone
insensitivity
syndrome.

Thank you.

GROWTH HORMONES

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