Download Pharmacology III Practical Sessions Growth Hormone

Growth Hormone
(somatotrophin)
Hormones
• 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”
Hormones
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.
Hormones
Regulation of secretion
̶
Sleep
Hypothalamus
Emotional Factors
GHRH
+
Exercise, fasting
SST
̶
̶
Anterior Pituitary
̶
GH
(DA, 5-HT & NE)
Drugs
GH
liver
IGF-1
Neurotransmitters
Target tissues
Liver, muscle,
bone, adipose
and other tissues
(dopamine agonists)
 GH Release
Hormones
• 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.
Hormones
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.
Hormones
Pharmacological
actions of GH
Hormones
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.
Hormones
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.
Hormones
• 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).
Hormones
• Therapeutic uses:

Somatropin is used in the treatment of GH
deficiency or growth failure in children.

Somatropin is also indicated for growth
failure due to Prader-Willi syndrome (PWS),
management of AIDS wasting conditions.
 GH an “antiaging” hormone. This has led to
off-label use of GH by older individuals and by
athletes seeking to enhance performance.
Route of administration:
 Somatropin is administered by subcutaneous or
IM injection
Hormones
• Adverse effects:
 Pain at the injection site.
 Edema, arthralgias, myalgias, flu-like
symptoms, and an increased risk of
diabetes.
Hormones
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)
Hormones
GH Deficiency
Hormones
II) GH overproduction
Mainly benign pituitary tumor (↑GH)
Other rare causes: ↑GHRH (hypothalamus)
Children
Gigantism
“increased longitudinal
growth”
Hormones
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)
Hormones
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)
Hormones
Diagnosis of GH disorders
Lab
Studies
Serum GH
GH
Deficiency
GH
Excess
Insufficient
Random GH measurement 
False results
Serum IGF-1
↓
↑
* Magnetic resonance imaging (MRI) is useful to confirm pituitary adenoma
Hormones
GH Deficiency
Following a
GH Excess
OGTT
Provocative test
Oral glucose tolerance test
(provoke GH release e.g.
insulin-induced
hypoglycemia - agents
as: arginine, L-dopa)
In response to a 75g
glucose challenge:
• Serum GH level < 10
ng/ml
 GH deficiency
• Serum GH level < 5
ng/ml  Severe GH
deficiency
↓
- Normal subjects:
suppress GH level <1 ng/ml
- Patients with excess GH
either:
fail to suppress or further
increase GH level.
Hormones
Assessment
 LARON SYNDROME.
What is carpal tunnel syndrome ?
Mention the relation between acromegaly &this
syndrome.
Hormones