GROWTH HORMONE Dr. Shaikh Mujeeb Ahmed

Objectives Factors influence growth beside growth hormone Metabolic effect of GH Relation between GH & insulin-like growth factors Functions of GH Factors influencing GH secretion GH abnormalities Hormones affecting growth beside GH

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 Hormone Hypothalamus Growth hormone release hormone (GHRH) Growth hormone inhibiting hormone (GHIH) aka somatostatin (SS) Anterior Pituitary Growth hormone (GH) Liver & other tissues Insulin-like growth factor (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) liver Insulin-like growth factor 1 (IGF-1) GH half-life is 20 – 30 min

Negative Feedback High levels of IGF-1 High levels of GH 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 Proportional body Adult 4'10" or shorter Proportional body Affects 1/10 000 Occurs in children GH absent during child’s development

Gigantism – Vertical Growth Excessive growth and height Continuous secretion of GH 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 Average brain size 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