1. Growth Hormone (somatotrophin)
Cairo University
Faculty of Pharmacy
Department of Pharmacology & Toxicology
Pharmacology III
Practical Sessions
Growth Hormone
(somatotrophin)

2. Hormones
Pharma-III Practical
• GH is the most abundant anterior pituitary hormone which is synthesized and secreted by somatotrophs.
“Somatotrophs are cells in the anterior pituitary These cells constitute 40-50% of anterior pituitary cells. They respond by releasing GH in response to GHRH (somatocrinin) or are inhibited by GHIH (somatostatin), both received from the hypothalamus”

3. GH release is PULSATILE;
Hormones
Pharma-III Practical
Daily GH secretion varies throughout life;
- secretion is high in children
- it reaches maximal levels at puberty and then
decreases in an age-related manner in adulthood.
GH release is PULSATILE;
GH is secreted in discrete but irregular pulses. Between these pulses, circulating GH falls to levels that are undetectable with most current assays .
The amplitude of secretory pulses is maximal at night, and the most consistent period of GH secretion is after the onset of deep sleep.

4. Regulation of secretion
Hormones
Pharma-III Practical
Regulation of secretion
Sleep
Emotional Factors
Exercise, fasting
Neurotransmitters
(DA, 5-HT & NE)
Drugs
(dopamine agonists)
 GH Release
Hypothalamus
GHRH +
SST ̶ ̶ ̶
Anterior Pituitary GH GH
liver
Target tissues ̶
Liver, muscle,
bone, adipose
and other tissues
IGF-1

5. Hormones Pharma-III Practical
Insulin-like growth factor 1 (IGF-1) (somatomedin C) is one of the mediators of GH action. It plays an important role in childhood growth and continues to have anabolic effects in adults.
IGF-1 is produced primarily by the liver as an endocrine hormone as well as other target tissues. Its production is stimulated by GH.
Almost every cell in the human body is affected by IGF-1, especially cells in muscle, cartilage, bone, liver, kidney, nerves, skin and lungs. IGF-1 regulates cell growth and development, especially in nerve cells as well as cellular DNA synthesis.

6. Physiologic Effects of Growth Hormone
Hormones
Pharma-III Practical
Physiologic Effects of Growth Hormone
it has two distinct types of effects:
Direct effects: are the result of growth hormone binding to its receptor on target cells.
For example on Fat cells (adipocytes).
Indirect effects: are mediated primarily by IGF-1. A majority of the growth promoting effects of growth hormone is actually due to IGF-I acting on its target cells.

7. Pharmacological actions of GH
Hormones
Pharma-III Practical
Pharmacological actions of GH

8. 1- Effects on Growth Hormones
Pharma-III Practical
1- Effects on Growth
GH stimulates the liver and other tissues to secrete IGF-I.
IGF-I stimulates differentiation and proliferation of chondrocytes (cartilage cells), resulting in bone growth.
IGF-I also appears to be the key player in muscle growth. It stimulates both the differentiation and proliferation of myoblasts.

9. 2- Metabolic Effects of GH
Hormones
Pharma-III Practical
2- Metabolic Effects of GH
Protein metabolism: GH stimulates protein anabolism in many tissues, increases amino acid uptake, increases protein synthesis and decreases oxidation of proteins.
Fat metabolism: GH enhances the utilization of fat by stimulating lipolysis and mobilization of FFA from adipose tissues.

10. Carbohydrate metabolism:
Hormones
Pharma-III Practical
Carbohydrate metabolism:
GH is one of the hormones that serves to maintain blood glucose within a normal range.
GH has anti-insulin activity  utilization of glucose by peripheral tissues
GH also  gluconeogenesis   hepatic glucose output
Both hyperglycemia   insulin secretion (hyperinsulinemia).

11. Clinical Disorders I) GH Deficiency
Hormones
Pharma-III Practical
Clinical Disorders I) GH Deficiency
Causes: ↓GHRH -Pituitary hypoplasia (↓GH ) - ↓IGF-1 (generation/actions) - Receptor defects
Children  Dwarfism
“Short stature with normal body proportion
Adults  Hypopituitarism
“↓ GH + other pituitary hormones (ACTH, TSH, FSH, LH, PRL) ”
Treatment:
Synthetic GH (Somatrophin)
Synthetic GHRH (Sermorelin)

12. Hormones
Pharma-III Practical
GH Deficiency

13. Hormones II) GH overproduction Pharma-III Practical Children
Mainly benign pituitary tumor (↑GH)
Other rare causes: ↑GHRH (hypothalamus)
Children
Gigantism
“increased longitudinal growth”

14. Hormones Pharma-III Practical Adults (after epiphyseal closure)
Acromegaly
enlargement of hands and feets (acral parts)  paresthesias and joint pain
coarsening of facial features, protrusion of lower jaw (prognathism)
soft tissue overgrowth, cardiomegaly
Gynecomastia and galactorrhea (hyperprolactinemia)

15. Hormones
Pharma-III Practical
Mortality rate is high in untreated acromegaly patients mainly due to tissues overgrowth causing:
cardiomegaly, upper airway obstruction and GIT malignancies.
Treatment of excess GH disorders:
- Synthetic Somatostatin (Octreotide)
- DA agonists (Bromocriptine)
- Surgical removal / Radiotherapy of the tumor
- GH Antagonists (Pegvisomant)

16. Diagnosis of GH disorders
Hormones
Pharma-III Practical
Diagnosis of GH disorders GH
Excess
GH Deficiency
Lab
Studies
Insufficient
Random GH measurement  False results
Serum GH ↑ ↓
Serum IGF-1
* Magnetic resonance imaging (MRI) is useful to confirm pituitary adenoma

17. ↓ Hormones Pharma-III Practical GH Deficiency GH Excess
Following a Provocative test
(provoke GH release e.g. insulin-induced hypoglycemia - agents as: arginine, L-dopa)
• Serum GH level < 10 ng/ml
 GH deficiency
• Serum GH level < 5 ng/ml  Severe GH deficiency
OGTT
Oral glucose tolerance test ↓
In response to a 75g glucose challenge:
- Normal subjects:
suppress GH level <1 ng/ml
- Patients with excess GH either:
fail to suppress or further
increase GH level.

18. Hormones
Pharma-III Practical