GROWTH HORMONE ENDO BLOCK 412 Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College Objectives The student should be able to: Identify the factors that affect growth beside the growth hormone. Identify the hormones that affect growth beside the growth hormone. Describe the metabolic effect of growth hormone. Identify the relationship between growth hormone and insulin-like growth factors. Explain the functions of the growth hormone. Define the factors that influence the growth hormone secretion. Describe the growth hormone abnormalities. Describe the functions of melatonin hormone. Explain the biological effect of melatonin hormone. Endocrine Control of Growth • Growth depends on growth hormone but is influenced by other factors as well – Genetic determination of an individual’s maximum growth capacity – An adequate diet – Freedom from chronic disease and stressful environmental conditions – Normal levels of growth-influencing hormones Hormones regulating growth • • • • • Thyroid Hormone Insulin: Stimulates IGF-1 Prolactin: Stimulates IGF-1 Testosterone Estrogen Growth • Other hormones besides growth hormone are essential for normal growth – Thyroid hormone • Growth severely stunted in hypothyroid children • Hypersecretion does not cause excessive growth – Insulin • Deficiency often blocks growth • Hyperinsulinism often spurs excessive growth – Androgens • Play role in pubertal growth spurt, stimulate protein synthesis in many organs • Effects depend on presence of GH – Estrogens • Effects of estrogen on growth prior to bone maturation are not well understood poorly Growth Stages - Regulation • Prenatal – Maternal factors, Fetal Insulin, & IGF • Growth in infancy – Genetic factors, GH production, Thyroid hormone, IGF • Adolescence- GH, Insulin, IGF & Sex hormone surge Growth hormone (GH) • A peptide hormone (~200 amino acids) • Also known as somatotropin: – tropic hormone that affects somatic cells Growth Hormone GH Function: Direct Effect • GH binds directly to its target cells: – bones & muscles • Stimulates growth – Hypertrophy: increase in size/volume of cells – Example: increase in bone thickness • Stimulates cell reproduction – Increased rate of mitosis – Hyperplasia: increase in the number of cells, proliferation rate – Example: increase in bone length • Stimulates cell metabolism – Increase protein synthesis – Increase fat breakdown for energy – Increase glycogen breakdown so that there is an increase in blood glucose levels to fuel cell growth Bone growth at the epiphyseal plate GH function on metabolism • Stimulates cell metabolism • Increase protein synthesis • amino acid transport through cell membrane • catabolism of protein • Increase fat breakdown for energy • Carbohydrate metabolism • • • • use of glucose for energy glycogen deposition in the cell blood glucose levels insulin secretion GH Function: Indirect Effect • Most growth occurs through the indirect method • GH acts as a tropic hormone • Signals the liver to produce Insulin-like Growth Factors (IGF) Growth Regulation: Neuroendocrine pathway Location Hypothalamus Hormone Growth hormone release hormone (GHRH) Growth hormone inhibiting hormone (GHIH) aka somatostatin (SS) Anterior Pituitary Growth hormone (GH) Liver & other Insulin-like growth factor tissues (IGF) IGF-1: Insulin-like Growth Factor 1 • targets almost every cell in the body including the muscle, cartilage, bone, and skin cells • Stimulates hypertrophy and hyperplasia of the cells Growth Hormone Regulation hypothalamus growth hormone releasing hormone (GHRH) growth hormone inhibiting hormone Somatostatin (GHIH) anterior pituitary growth hormone (GH) GH half-life is 20 – 30 min liver Insulin-like growth factor 1 (IGF-1) Negative Feedback • High levels of IGF-1 – Stimulates GHIH/SS – decreased secretion of GH • High levels of GH – inhibits GHRH GH Secretion • Secreted in bursts (not continuous) • GH his released most during sleep – optimal at night time – Changing sleeping pattern affects GH release • GH production declines with age Increasing GH Production • • • • Exercise regularly 8 hours of sleep Protein-rich diet Avoid Stress GH Associated Disorders • Dwarfism • Gigantism • Acromegaly Dwarfism • Deficiency in GH • Short stature – Adult 4'10" or shorter • Proportional body • Affects 1/10 000 • Occurs in children – GH absent during child’s development • 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. Gigantism – Vertical Growth • Excessive growth and height • Continuous secretion of GH • Hyperglycemia or full blown diabetes mellitus • Open epiphyseal plate – Affects bone growth length • Occurs during childhood World’s Tallest Man: Robert Wadlow (1918-1940) 8 feet 11 inches and 439 pounds when he died Tallest person alive • Sultan Kosen • born in Turkey • 8 feet 1 inch http://www.youtube.com/watch?v=ODFHC2XCtjU http://www.youtube.com/watch?v=Rf-lcBzZwC4 Gigantism Cause • Pituitary Adenoma – Tumour formed by pituitary gland – Secretes excessive GH / IGF-1 – Non cancerous • Average brain size – Skull grows but brain size stays the same, thus the brain function is unchanged Gigantism Problems • Poor blood flow due to large body • Increased muscle mass but weaker muscle – Excess GH produces salt in muscle tissues – Muscles swell with water – Results in disproportional muscle growth weaker muscles Comparing Growths Acromegaly – Lateral Growth • Increased GH secretion in adults • Closed epiphyseal plate – Bone lengthening stopped • Bone width increases • Slow progression Acromegaly: Physical Effects • Bone thickens – Forehead expands – Eyebrow ridges bulge outwards – Cheekbones more prominent – Mandible enlarges and pushes lower teeth outwards and become widely space Acromegaly: Physical Effects • Soft tissue harden – Deeper voice because larynx enlarges – Bigger tongue and lips that affects breathing – Cartilage in nose enlarges making nose broader Acromegaly: Effect on Muscles • Impaired Movements – Enlargement of bones crushes peroneal nerve in knee – Nerve carries messages to move foot and lower leg – Nerve cannot send messages to leg to trigger walking motion • Also cause muscle numbness • Leads to early death Acromegaly: Heart Defects • Heart tissue stiffen – heart cannot contract and relax – Ventricle harder to fill up • Heart grows bigger in order to pump out sufficient blood Acromegaly: Lung Defect • As bones grow, rib cage expands • Diaphragm is stretched thin and loses elasticity • Breathing is reduced The Pineal Gland • The pineal gland is a small, cone – shaped structure located in the center of the brain, diencephalon. • The pineal gland is composed of pinealocytes & glial cells. • Connects endocrine with nervous system Functions • Secretion of the Hormone Melatonin • Regulation of Endocrine Functions • Conversion of Nervous System Signals to Endocrine Signals • Causes Feeling of Sleepiness • Influences Sexual Development • Precursor of melatonin is serotonin. • Synthesis and secretion of melatonin is affected by light exposure to the eyes. Biological Effects of Melatonin • Helps keep body’s circadian rhythms in synchrony with light-dark cycle • Effects on Reproductive Function • Anti-gonadotropic • Effects on Sleep and Activity • Acts as antioxidant to remove free radicals • Alterations in melanin pigment distribution References Human physiology, Lauralee Sherwood, seventh edition. Text book physiology by Guyton &Hall,11th edition. Physiology by Berne and Levy, sixth edition. 38