Growth hormone

Objectives The student should be able to: Identify the hormones that affect growth. Describe the metabolic effects of GH. Identify relationship between GH and insulin-like growth factors. Explain the functions of GH. Define the factors that influence GH secretion. Describe GH abnormalities.

Hormones regulating growth 1) Growth hormone. 2) Thyroid hormones: Growth is severely stunted in hypothyroid children. Hypersecretion does not cause excessive growth. 3) Insulin & IGF 1: Deficiency often blocks growth. Hyperinsulinism often spurts excessive growth. 4) Androgens: Play a role in pubertal growth spurt, stimulate protein synthesis in many organs. Effects depend on presence of GH.

Growth hormone (GH) (= Somatotropin) Somatotropin: tropic hormone that affects somatic cells. Growth hormone is a 191- amino acid, single-chain synthesized, stored, and secreted by somatotropic cells within anterior pituitary gland. It is metabolized rapidly in liver. Short duration of action (20 minutes).

GH Functions Stimulates growth: Hypertrophy: increase in size of cells. Example: increase in bone thickness. Stimulates cell reproduction: Increased rate of mitosis. Hyperplasia: increase in number of cells & proliferation rate. Example: increase in bone length.

Metabolic functions of GH 1) Protein synthesis (Anabolic): Adequate insulin & carbohydrates necessary for GH to be effective.  Amino acid Transport inside cells  protein accumulation in all cells.  DNA Transcription to form mRNA  protein synthesis.  RNA Translation  protein synthesis. 2) Lipolytic & Ketogenic effect:  Mobilization & use of fatty acids for supplying energy. So, excess hormone  ketosis.

3)  Utilization of carbohydrate for energy production:  Uptake of glucose by cells  blood glucose (diabetogenic effect).  Use of glucose for energy production due to  utilization of fatty acids for energy. It inhibits hexokinase enzyme  inhibits glucose uptake by muscles (opposite to insulin effect).  Hepatic glucose output (stimulates glycogenolysis).  Insulin output  burn out of beta cells of pancreas (pituitary diabetes).

GH Function (Indirect Effect) Most growth occurs through the indirect method. GH acts as a tropic hormone acting on the liver to produce Insulin-like Growth Factor-1 (IGF-1). Insulin-like growth factor I (somatomedin C)   growth promoting activities in many tissues and cartilage with a prolonged duration of action (20 hours).

Chondrogenesis & bone growth In young: (before union of epiphysis) GH stimulates chondrogenesis (proliferation of epiphyseal cartilage & widening of epiphyseal plates). Stimulation of osteoblasts   bone matrix   length of long bones. In adult: (after union of epiphysis) linear growth is impossible.

Growth Hormone Regulation hypothalamus growth hormone releasing hormone (GHRH) growth hormone inhibiting hormone Somatostatin (GHIH) anterior pituitary growth hormone (GH) liver Insulin-like growth factor 1 (IGF-1) GH half - life = 20 - 30 min.

Negative Feedback High levels of IGF-1 Stimulates somatostatin GHIH (=SS)  decreased secretion of GH. High levels of GH inhibits GHRH.

GH Secretion Secreted in bursts (not continuous). GH is released most during sleep: optimal at night time. Changing sleeping pattern affects GH release. GH production declines with age.

Factors affecting GH secretion Factors stimulate GH Factors inhibit GH 1- Hypoglycaemia 2- Protein rich diet 3-  Amino acid in blood (as Arginine) 4- Exercise 5- Stress 6- Sleep (8 hours) 7- Glucagon 8- Ghrelin 1- Hyperglycemia 2- Free fatty acids 3- Excess GH feeds back to inhibit its own secretion 4- Excess Cortisol

HYPOPITUITARISM 1- DWARFISM  Growth hormone during childhood. Characterized by: Proportionate dwarfism (short stature): Features of body are proportionate to each other, but rate of development is decreased. Patient at age of 20 may has body development of a child at 10 years. No thyroid deficiency. No adrenocortical deficiency. No mental retardation (Wise person with small stature). Treatment: Synthetic Growth hormone

DWARFISM In one type of dwarfism (the African pygmy and the Lévi-Lorain dwarf), the rate of growth hormone secretion is normal or high, but there is a hereditary inability to form somatomedin C, which is a key step for the promotion of growth by growth hormone.

2- Simmond’s disease (=Pituitary Cachexia) Cause: a) Damage of pituitary by Ischemia & Tumor. b) Postpartum hemorrhage  pituitary necrosis (Sheehan's Syndrome). C/P: Panhypopituitarism ( GH, TSH, ACTH, FSH & LH). Premature senility (= Progeria), loss of hair and body weight & shrunken skin. Asthenia (muscular weaknes) & ↓ Mental Activity. Thyroid deficiency  low BMR &  serum cholesterol. Adrenocortical deficiency  hypoglycemia. Gonadal deficiency (hypogonadism).

HYPERPITUITARISM 1- Gigantism (Vertical Growth)  GH by Acidophils in anterior pituitary before union of epiphysis (in children). Cause: Pituitary Adenoma Tumour formed by pituitary gland. Secretes excessive GH / IGF-1 Non cancerous.

Gigantism Clinical picture: All body tissues grow rapidly i.e. general overgrowth of skeleton  person becomes a Giant. High BMR (direct effect of GH on metabolic activity + effect of TSH). Hyperglycemia & diabetes mellitus  lowered general resistance. Low gonadotropins  Hypogonadism. Short life, if survives till adulthood  Acromegaly.

World’s Tallest Man Robert Wadlow (1918-1940) 8 feet 11 inches and 439 pounds when he died

Acromegaly (Lateral Growth) Acro = extremity as hands and feet. Megaly = large. ↑↑ GH by Acidophil After union of epiphysis (in Adult). Closed epiphyseal plate → Bone lengthening stopped. Bone width increases. Slow progression

Physical Effects of Acromegaly Bone thickening Protruding lower jaw (= prognathism) & upper jaw, supraorbital ridge & separation of teeth coarsening of facial features (bone deformities). Hands and feet (=acral parts) are enlarged(thick, broad fingers). Bowing of spine (kyphosis).

Physical Effects of Acromegaly Soft tissue enlargement: - Deeper voice because larynx enlarges - Bigger tongue and lips that affects breathing - Cartilages in nose and ears enlarge making nose and ears broader. Impaired muscle movements: Enlargement of bones crushes peroneal nerve in knee. Nerve cannot send messages to leg to trigger walking motion.

Acromegaly: Heart Defect Cardiac effects: Heart grows bigger in order to pump out sufficient blood.