1
GROWTH HORMONE
         &
    GROWTH CURVE
2   Dr. Ismoth Ara Jerin
    Resident
    MD (Phase-A) Part-I
    Department of Physiology
    BSMMU
OVERVIEW
 Introduction to GH
 Chemistry & Biosynthesis
 Mechanism of action
 Metabolic effects of GH
 Factors affecting GH secretion
 Growth curve
 Abnormalities of GH secretion
                                   3
  INTRODUCTION TO GH
•Also called somatotropic hormone
or somatotropin.
•GH causes growth of all tissues of the
body that are capable of growing .
                                          Fig: Pituitary gland
                                          in Sella turcica.
•Secreted from anterior pituitary.
                                                            4
                                          (Tortora 2012)
Fig: Hypothalamic-hypophysial portal system
                                                     5
                                       (Hall 2012)
 Cells of anterior
Pituitary:
1. Somatotropes-(30-
   40)%
2. Corticotropes-20%
3. Thyrotropes-(3-5)%
4. Gonadotropes-(3-5)%
5. Lactotropes-(3-5)%
                         Fig:- Cellular structure
                         of anterior pituitary
                                                    6
                                      (Hall 2012)
    CHEMISTRY & BIOSYNTHESIS
 Chemically GH is protein in nature.
 Single chain of 191 amino acids.
 M.W -22005
 Long arm of human chromosome
17contains the growth hormone-hCS
Cluster that contains 5 gene-              Fig:- Structure of GH
  one hGH-N
  one hGH-V
  Two hCS
  one hCS pseudogene
                                                                7
                                        (Barrett et al. 2012)
SYNTHESIS OF GH
                  (Boron & Boulpaep 2012)
   Normal concentration of GH in plasma:
    ✓   In adult- 1.6-3ng/ml
    ✓   In child / adolescent- 6ng/ml
   Half life:-6-20 min
   Daily secretion of GH- 0.2-1mg/d in adults
   Metabolism- rapidly metabolized in liver.
                                                 9
Fig: Insulin & IGF-1 receptors   Fig: GH receptor
                                                      10
                                 (Boron & Boulpaep 2012)
MECHANISM OF ACTION OF GROWTH
HORMONE:
                                             11
                     (Barrett et al. 2012)
METABOLIC EFFECT OF GH :
     On protein metabolism:
1.    ↑ the transport of AA through the cell
      membrane.
2.    ↑ the RNA translation to cause protein
      synthesis by ribosome.
3.    ↑ nuclear transcription of DNA to form RNA.
4.    ↓ catabolism of protein and amino acid.
                                                    12
On fat metabolism:
 ↑ Mobilization of fat from adipose tissue.
 ↑ Free fatty acid level in blood.
 ↑ Utilization of fatty acid for energy.
On carbohydrate metabolism:
 ↓ Glucose uptake in tissues (e.g skeletal muscle
  & adipose tissue).
 ↑Glucose output by liver.
 ↑ Insulin secretion but resistant to insulin action.   13
On electrolytes:
   ↑ GI absorption of Ca++.
   ↓ Na+ & K+ excretion (independent of adrenal
    gland action) .
                                                   14
On bones:-
 ↑ Bone protein deposition by osteogenic &
  chondrocytic cells.
 ↑ Rate of cell multiplication.
 Conversion of chohdrocytes to osteogenic
  cells.
 Thus, results in deposition of new bones.
                                              15
                 SOMATOMEDINS
   Also called IGF.
   At least 4 Somatomedins have been
    identified.
   Most important one is Somatomedin C /IGF-1
                                                         16
                                 (Barrett et al. 2012)
SOMATOMEDIN C
  Secreted by Liver, Cartilage & other tissues
  M.W-7500
  Plasma level-10-700ng/ml; peaks at puberty.
  Half life- 20 hrs.
                                                            17
     Fig: Serum IGF-1 & rate of height increase .
                                       (Boron & Boulpaep 2012)
   Somatomedins have potent direct effect on all
    aspects of bone growth.
     Fig: Direct & indirect effect of growth hormone          18
                                      (Barrett et al. 2012)
METABOLIC EFFECT OF EXCESSIVE GH
   Ketogenic effect:
                 Excessive GH
        Mobilization of fat in large amount
        from adipose tissue
        Excessive amount of acetoacetic acid formed
        by liver & released into body fluids
                    Ketosis                           19
   Diabetogenic effect:
             Excess GH causes ↑ FA
        concentration in blood above normal
        ↓sensitivity of liver & skeletal muscle to insulin
            Results in insulin resistance
        Decrease glucose uptake in tissues
        Increase glucose production by liver
                                                             20
 Increased blood glucose concentration
Compensatory increase in insulin secretion
                β-cell burn out
          Diabetogenic effect of GH
                                             21
HYPOTHALAMIC CONTROL OF GH SECRETION
 Fig: Feedback control
 of GH secretion
                                                 22
                         (Barrett et al. 2012)
                        GHRH
Combines with receptor on the outer surface of somatotropes
              Activation of adenylyl cyclase system
              ↑ intracellular cAMP level
Short-term effect                     Long-term effect
 ↑ Ca++ transport into the cell       ↑ transcription in nucleus
  Fusion of GH secretory vesicle       Stimulates the synthesis
  with cell membrane                   of new GH
                                                            23
  Release of GH into blood
FACTORS AFFECTING GH SECRETION
                                         24
                           (Hall 2012)
Fig: Typical variations in GH secretion throughout the day
                                                          25
                                            (Hall 2012)
Fig: Effect of extreme
protein deficiency on
plasma concentration
of GH in Kwashiorkor
                                       26
                         (Hall 2012)
Plasma concentration of GH in different age:
                                                         27
                                           (Hall 2012)
GROWTH PERIOD:
                                         28
                 (Barrett et al. 2012)
GROWTH CURVE
                                       29
               (Barrett et al. 2012)
ABNORMALITIES OF GH SECRETION
   Panhypopituitarism:
          This term means decreased secretion of
    all the anterior pituitary hormones.
It may be –
a) Congenital.
b) Sudden onset at any time during life.
❖    Most often it results from pituitary tumour that
     destroys the pituitary gland.
                                                        30
   Dwarfism:
✓   Mostly due to panhypopituitarism during
    childhood.
✓   Physical parts of the body develop in appropriate
    proportion but the rate of development is greatly
    decreased.
✓   The person dosen’t pass through puberty due to
    lack of gonadotropic hormone.
✓   1/3rd case- GH is deficient only & person mature
    sexually.                                           31
Fig: Normal & abnormal growth                           32
                                (Barrett et al. 2012)
   Le׳vi-Lorain Dwarf & African pygmy:
✓   GH level –Normal / high
✓   Hereditiary inability to form Somatomedin C.
                    Fig: African pygmy                    33
                                          (www.pygmies.org)
   Panhypopituitarism in adult:
It results from:-
1. Craniopharyngioma
2. Chromophobe tumours
3. Thrombosis of pituitary blood
    vessels.
Patient is –
•Lethargic
•Gaining weight
•Sexual function is lost           34
   Treatment with GH:
✓   GH is produced in E.coli by recombinant DNA
    technology & available for treatment purpose.
      Fig : E.coli
✓Dwarfs with pure GH deficiency can be                      35
completely cured if treated early in life.
                                     (www.studentconsult.com)
EFFECTS OF HYPER SECRETION OF GH
    Gigantism:
 •   Excess secretion of GH before the
     epiphyseal closure.
 •   Cause-Acidophilic tumour in
     anterior pituitary.
 •   Clinical feature-
        ▪   Abnormal height- upto 8 feet.
        ▪   Hyperglycemia.
        ▪   Full blown DM- in 10% case
 •   Eventually Panhypopituitarism
     develop due to destruction of                       36
     pituitary gland by tumour.
                                            (Sherwood 2012)
   Acromegaly:
•   Occurs due to excesses secretion of GH in adults
    after epiphyseal closure.
•   The person cannot grow taller, but the bones become
    thicker & soft tissue can continue to grow.
•   Cause-Acidophilic tumour in anterior pituitary.
                                                       37
   Clinical feature:
•   Enlargement of hands & feets.
•   Potrusion of lower jaw.
•   Bosses on the forehead.
•   Enlargement of supraorbital
    ridge, portion of vertebrae.
•   Kyphosis.
•   Enlarged tongue & liver.
•   Kidney become greatly
    enlarged.                       Fig:Acromegalic patient
                                                          38
                                            (Hall 2012)
                           39
(www.studentconsult.com)
BIBLIOGRAPHY
Books:
1. Guyton A C, Hall J E, Text book of medical Physiology,12th edition, India,
   Elsevier,2012.
2. Barret K E, Barman S M, Boitano S ,Brooks H L,Ganong’s review               of
   medical Physiology,24th edition, India, McGraw-Hill,2012.
3. Tortora G.J, Derrickson B,Principles of Anatomy & Physiolgy, 13th ed,
USA, John Wiley & sons,2012.
4. Sherwood lauralee, Fundamentals of human physiology,4th edition,
  Brooks/Cole,2012,Canada.
5. Boron W.F, Boulpaep E.L, Medical Physiology, 2nd ed, USA, Elsevier, 2012.
Website:
1. www.studentconsult.com                                                      40
2. www.pygmies.org
ACKNOWLEDGEMENT
-Respected teachers
- Seniors
- Colleagues
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THANK
 YOU
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