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.
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