2. Human Growth Hormone
• It is a Polypeptide hormone secreted from anterior pituitary in
response to growth hormone releasing hormone (GHRH) from
hypothalamus. Its highly hydrophobic proteins consist from 191
amino acid residues and its molecular weight about 22125 Daltons.
3. ACTIONS OF GROWTH HORMONE:(GH)
• Actions of GH are of 2 types.
• DIRECT CATABOLIC actions mainly (lipolysis and glycogenolysis)
• INDIRECT ANABOLIC actions
The Indirect actions are via the somatomedins
Somatomedins are polypeptides synthesized mainly in liver
• Also synthesized in kidneys ,cartilage & skeletal muscles.
• In humans, most important is Somatomedin C, also called as Insulin-
like growth factor (IGF-I), secreted due to the action of GH mainly on
liver & to a small extent in other organs.
4. Actions of Growth Hormone
1) Stimulation growth of bones, cartilage &
connective tissue; mediated mainly via Somatomedin C
(IGF-1)
a) On Bones & cartilage (Before epiphyseal closure):
GH causes liver to secrete IGF-1, which in turn causes
• Proliferation of chondrocytes (Chondrogenesis)
• Appearance of osteoblasts
• Stimulation of DNA & RNA synthesis
• Collagen formation in cartilage
Result- Increase in thickness of epiphyseal cartilagenous end
plates. Resulting in linear skeletal growth; seen maximally
during puberty & causes pubertal growth spurt.
5. GH action on bones
b) After Epiphyseal closure:
• No increase in bone length
• Increase in bone thickness or widening through
periosteal growth.
• Increased protein synthesis in most organs causing
hyperplasia, hypertrophy; increased tissue mass and
increased organ size (oraganomegaly).
6. 2) Actions of GH on Metabolism
a) Effect of GH on Carbohydrate Metabolism:
This is a direct action of GH. Does not need IGF
• GH is a Diabetogenic hormone ie; increases
plasma glucose
• GH causes Hyperglycemia by increasing Hepatic
glucose output
• Decreases peripheral utilization of glucose (Anti-
Insulin Effect)
7. Metabolic actions of GH
b) Effect of GH on Protein metabolism: Indirect
action which requires IGF
• GH is a Protein Anabolic Hormone
• It increases protein synthesis in muscle & increases
lean body mass
• Also increases protein synthesis in organs & increases
organ size
8. Metabolic actions of GH
C) On Fat metabolism:
• GH has a direct catabolic effect - mobilizes fat from
adipose tissues by increasing lipolysis. (Does not
require IGF for this action)
• Increases plasma free fatty acids (FFA), which are
further used for Gluconeogenesis
• Ketogenic- Produces FFA which undergo hepatic
oxidation and form ketone bodies
9. Other actions of GH
• Stimulates mammary growth & milk production (as
it has structural similarity to PRL)
• Stimulates erythropoiesis
• Stimulates calcium absorption from GIT
10. Regulation of GH secretion
A) Role of Hypothalamus: Hypothalamus regulates GH
secretion via Growth hormone releasing hormone
(GHRH) and GH inhibiting hormone (GHIH /
Somatostatins)
12. Clinical correlates of Anterior Pituitary
DWARFISM: Occurs due to GH deficiency
• Results in Short stature/Stunted growth
Causes:
• Pan hypopituitarism (lack of all anterior pituitary
hormones)
• Decreased GHRH
• Decreased IGF-1 secretion (GH receptor defect)
13. Pituitary Dwarfism
• GH deficiency results in proportionate short stature
due to growth retardation (short stature). Individuals
are referred to as Dwarfs.
• Other associated features seen in GH deficiency are-
Decreased hair growth due to decreased protein
synthesis, fasting hypoglycemia.
15. Growth Hormone excess –
Before Puberty
GIGANTISM : Is seen due to overproduction of GH during
adolescence, before puberty (before epiphyseal closure) –
Results in excessive growth of long bones-↑↑Height
Clinical features:
• Tall stature (2.5 meters)
• Large hands & feet
• Other associated features – Bilateral Gynaecomastia
(enlargement of breasts due to structural similarity of GH to
Prolactin)
• Coarse facial features due to increased tissue proliferation
16. 12 year old boy with Pituitary Gigantism measuring 6’5” with his mother.
17. GH excess after Puberty
ACROMEGALY:
Occurs due to excessive secretion of GH during adulthood
(after epiphyseal closure)
Causes of Acromegaly are:
- tumor of anterior pituitary
-Hypothalamic GHRH secreting tumors
Clinical features are mainly seen due to excess growth of
cartilaginous & peripheral parts & other features due to
increased metabolic actions
18. Clinical features of Acromegaly
• Prognathism - elongation & widening of mandible
• Prominent eyebrow
• Facial changes seen are described as ACROMEGALIC FACIES –
thickening of skin & coarse facial features - proliferation of
connective tissue resulting in facial edema
• Kyphosis - periosteal growth of vertebrae
• Enlarged hands & feet periosteal growth of metatarsals &
metacarpals bone
• Increased plasma glucose levels- due to metabolic actions
19.
20. Prolactin
• Prolactin (PRL) is a single chain polypeptide
• Receptors resemble GH receptors
• Structurally similar to GH
• Increases during pregnancy & lactation
• Predominant action on mammary gland
• Also inhibits gonadotrophic hormone secretion
21. Physiological actions of PRL
• PRL is responsible for Lactogenesis (initiation of
lactation) & galactopoiesis (continuation of lactation)
• Stimulates milk production in the breasts by formation
of Casein & Lactalbumin
• Stimulates breast development along with Estrogen
during pregnancy
• Inhibits Ovulation by decreasing secretion of LH & FSH
22. Clinical aspects
Hyperprolactinemia: PRL excess results from:
• Hypothalamic lesions – due to loss of inhibitory
control of PIF (Dopamine) on PRL secretion
• Prolactinomas – PRL secreting tumors of Anterior
Pituitary
Clinical Features:
• Galactorrhea
• Amenorrhea (Lack of Menstrual cycles) because PRL
inhibits release of FSH & LH .
24. The posterior pituitary gland
Composed mainly of cells called ‘Pituicytes’, which act as
packing & supporting cells.
Stores & releases hormones into the close capillaries.
These hormones are produced in hypothalamus.
25. The posterior pituitary gland hormones
Posterior pituitary gland releases 2 hormones:
1. Antidiuretic hormone (ADH), or arginine vasopressin
(AVP).
2. Oxytocin
Both hormones are produced in hypothalamic nuclei:
- Supraoptic nucleus( SON) (ADH + 1/6 oxytocin)
- Paraventricular nucleus (Oxytocin + 1/6 ADH)
Both hormones are polypeptides, each contains 9 mino acids.
Both are transported slowly along the hypothalamic-hypophyseal
tract’ in combination with carrier protein called ‘neurophysin’, to
the nerve endings in the posterior pituitary gland where they are
stored.
26.
27. The posterior pituitary hormones –
1. ADH (vasopressin):
Antidiuretic hormone (ADH), or arginine vasopressin
(AVP), is produced mainly in SON of hypothalamus.
ADH activates (2) second messenger systems:
1. cAMP
2. IP3/Ca2+
28. Action of ADH
ADH has 2 main effects:
1. water re-absorption (retention) by distal tubules &
collecting ducts of the kidneys decrease osmotic pressure
of the blood.
* This effect is regulated by V2 receptors, through the
action of cAMP.
2. Contraction of vascular smooth muscles generalized
vasoconstriction.
* This effect is regulated by V1 receptors, through the action
of IP3/Ca2+.
29. Abnormalities of ADH release – Hyposecretion:
Lack of ADH Diabetes insipidus.
2 types of DI: a. Neurogenic (central, or cranial) …
Problem in Hypothalamus or Post pituitary
gland; could be 1ry or 2ry.
R/: ADH.
b. Nephrogenic
failure of receptors to respond to ADH Inherited or
Acquired
No ADH is needed as treatment.
Symptoms: Polyurea 20 L/day (N 1.5 L/d), Polydepsia,
specific gravity of urine (diluted urine),
plasma osmolality.
30. The posterior pituitary hormones –
2. Oxytocin:
Produced mainly in the paraventricular nucleus of
the hypothalamus.
Action of oxytocin
1.Contraction of smooth muscles of the uterus
enhance labor.
2.Contraction of mammary gland myoepithelial cells
of the alveoli & the ducts Ejection of milk as a
reflex in lactating women.
3. Oxytocin is concerned with releasing or ejection of
milk, while prolactin is concerned with synthesis &
production of milk.
31. Control of oxytocin release
1. Stimulation of nipple (suckling reflex) oxytocin.
2. Visual or auditory stimuli from the baby oxytocin
secretion.
3. Distension of uterus & stretching of cervix during
delivery oxytocin release.
4-Psychological & emotional factors, e.g. Fear, anxiety &
pain oxytocin.
5-Hormones: a. progesterone uterine sensitivity to oxytocin.
b. estrogen uterine sensitivity to oxytocin.
