Animal Physiology II Lecture Notes - SC/BIOL 3070

ANIMAL PHYSIOLOGY II SC/BIOL 3070 - 4.0 Growth Suggested readings: Sherwood pgs. 279-281 and 291-297 Growth 1 Outline Learning Objectives: Introduction and growth related terms Growth in vertebrates: ○ process of long bone growth ○ endocrine control of growth consequences of abnormal GH activity By...

ANIMAL PHYSIOLOGY II SC/BIOL 3070 - 4.0 Growth Suggested readings: Sherwood pgs. 279-281 and 291-297 Growth 1 Outline Learning Objectives: Introduction and growth related terms Growth in vertebrates: ○ process of long bone growth ○ endocrine control of growth consequences of abnormal GH activity By Mikael Häggström, used with permission. https://commons.wikimedia.org/w/index.php?curid=6699074 Growth 2 Introduction to growth What is growth? - an increase in body size due to the organized addition of new tissue ➨ growth is not synonymous with weight gain since this can occur as a result of excess water or fat retention ➨ growth requires net synthesis of proteins - Our focus will be on different stages of growth after birth: ➨ mammals: baby (child), juvenile (adolescence), adult Growth 3 Introduction to growth Changes in growth can occur due to: a) hypertrophy: enlargement in cell size b) hyperplasia: increase in cell number c) production of extracellular substances (e.g. extracellular matrix) Growth 4 Introduction to growth What factors influence/control body growth? 1) Extrinsic Factors a) adequate diet: adequate total protein and ample essential amino acids to accomplish protein synthesis for growth (particularly important for first two years of life in humans) b) freedom from chronic diseases and stressful environments: ➨ glucocorticoids (i.e. stress hormones) are catabolic and can exert several potent anti-growth effects Growth 5 Introduction to growth What factors influence/control body growth? 2) Intrinsic Factors a) genetics: e.g. mammals cannot exceed a genetically determined maximum by eating more than an adequate diet ➨ results in obesity (storage of fat), which is not growth b) normal concentrations of growth-influencing hormones Growth 6 Introduction to growth Growth hormone (GH) is absolutely essential for growth and is synthesized and secreted by somatotropes in the anterior pituitary GH stimulates growth of both soft tissue and the skeleton: 1) promotes soft tissue growth - increases cell number (hyperplasia) by stimulating cell division and preventing apoptosis (programmed cell death) - increases cell size (hypertrophy) by favoring the synthesis of proteins and inhibiting their degradation 2) promotes bone growth - increases thickness and length of long bones ➨ determines body height, the most dramatic effect of GH Growth 7 Long bone growth Epiphysis Compact bone Diaphysis - epiphysis: rounded end of long bone ➨ found at its joint with an adjacent bone Epiphysis - diaphysis: shaft of long bone Epiphyseal plate - epiphyseal (growth) plate: layer of cartilage between the epiphysis and diaphysis at each end in a growing bone ➨ site of longitudinal bone growth Diaphysis Growth Fig. 7-14a, p294 8 Long bone growth Epiphysis Epiphyseal plate chondrocytes Diaphysis osteoblasts Sherwood Fig. 7-14, p294 - chondrocytes: cells that produce and maintain the cartilage ➨ cartilage: uncalcified bone - osteoblasts: bone-forming cells that deposit mineralized bone tissue - osteoclasts: bone breakers that dissolve bony tissue on the inner surface adjacent to the marrow cavity. Growth 9 Long bone growth Epiphysis Epiphyseal plate Diaphysis Sherwood Fig. 7-14, p294 Bone Growth/Lengthening: 1) chondrocytes on outer edge of plate next to the epiphysis proliferate, temporarily widening the plate and adding length to the bone 2) new chondrocytes are formed at the edge, while the older chondrocytes progress toward the diaphysis and enlarge (hypertrophy) 3a) extracellular matrix surrounding the oldest hypertrophied cartilage becomes calcified by deposition of calcium salts Growth 10 Long bone growth Epiphysis Epiphyseal plate Diaphysis Sherwood Fig. 7-14, p294 Bone Growth/Lengthening: 3b) since extracellular matrix is calcified, the old nutrient-deprived chondrocytes die 4) osteoclasts remove the dead chondrocytes and calcified matrix that imprisoned them leaving open cavities within the matrix 5) osteoblasts move up from diaphysis and deposit bone over persisting remnants of disintegrating cartilage Growth 11 Long bone growth Bone Growth/Lengthening: - at end of adolescence (after puberty), chondrocyte precursor cells are exhausted and the epiphyseal bone fuses with the diaphyseal bone ➨ epiphyseal closure epiphyseal line epiphyseal plate Growth 12 Endocrine control of growth - GH also exerts metabolic actions unrelated to growth - metabolic actions are directly mediated though GH receptors in target tissues (adipose tissue, skeletal muscle, liver) and include: 1. 2. 3. Growth increased lipolysis, elevating plasma fatty acid levels decreased glucose uptake by muscle, conserving plasma glucose for the brain increased glucose output by the liver Fig. 7-15, p295 13 Endocrine control of growth - GH exerts its growthpromoting effects indirectly - Indirect actions involves stimulating the production of insulin-like growth factors (IGFs) - IGFs are mainly produced by the liver (acting as a peripheral endocrine gland) and includes insulin-like growth factor I (IGF-1) Growth Fig. 7-15, p295 14 Endocrine control of growth Insulin-Like-Growth Factor-I (IGF-I): - stimulates chondrocytes within the epiphyseal plate to proliferate and also express and secrete IGF-1 ➨ this stimulates further proliferation by autocrine/paracrine release of IGF-1 by chondrocytes Growth 15 Endocrine control of growth Insulin-Like-Growth Factor-I (IGF-I): - stimulates chondrocytes within the epiphyseal plate to proliferate and also express and secrete IGF-1 ➨ this stimulates further proliferation by autocrine/paracrine release of IGF-1 by chondrocytes - other factors that affect IGF-I production include: ➨ nutrition – inadequate food intake reduces IGF-I production ➨ age – IGF-I levels increase during the pubertal growth spurt ➨ gonadotropins (FSH, LH) and sex hormones stimulate IGF-I production in reproductive organs (i.e. ovaries and testes) Growth 16 Endocrine control of growth Two major factors in GH control: 1) growth hormone-releasing hormone (GHRH) from the hypothalamus stimulates the production and secretion of GH in the anterior pituitary ➨ GHRH is subject to negative feedback by GH and IGF-I - GHRH activates anterior pituitary somatotropes by binding a GPCR, which increases cAMP (Gs) and elevates GH secretion Growth Fig. 7-15, p295 17 Endocrine control of growth Two major factors in GH control: 2) somatostatin (SST) from the hypothalamus inhibits the production and release of GH ➨ SST is subject to positive feedback by GH and IGF-1 - SST also elicits control of somatotropes through GPCR, which lowers cAMP (Gi) and decreases GH secretion - due to these positive and negative feedback mechanisms, GH release into the blood is pulsatile Growth Fig. 7-15, p295 18 Other regulators of GH secretion - circadian rhythm: GH secretion is high at night, low during the day ➨ one hour after onset of deep sleep : ⇧ GH - hypoglycemia or exercise or stress: ⇧ GH - thyroid hormone: exerts a permissive action (i.e. increases GH receptors) - cortisol: generally antagonizes the action of GH in protein metabolism - ghrelin, a potent appetite stimulator released from the stomach: ⇧GH, presumably to coordinate growth with nutrient acquisition Growth 19 Consequences of abnormal GH activity Dwarfism - due to the hyposecretion of GH (or inability to respond to GH) - characterized by short stature (defined as an adult height of less than 4 feet 10 inches) ➨ Laron syndrome – malfunctioning GH receptors (therefore, tissues fail to respond to GH) Growth 20 Consequences of abnormal GH activity Gigantism - characterized by abnormally tall stature (defined as an adult height between 7 – 9 feet) - due to hypersecretion of GH during childhood and rapid growth of all body tissues Robert Wadlow ➨ the tallest man known to have lived (at 8 feet 11 inches) - shown with his father (at 6 feet 0 inches) Growth 21 Consequences of abnormal GH activity Acromegaly - due to hypersecretion of GH during adulthood - results in: ➨ coarsening of facial features, swelling of soft tissue in hands and feet, increase in length and thickness of mandible ➨ hypertrophy of liver, kidneys and tongue ➨ may also result in cardiovascular and respiratory diseases A B C progression of acromegaly: A = 16 y.o. B = 33 y.o. C = 52 y.o. Growth 22 Regulation of Fetal Growth and Development - GH appears to be important for post-natal growth only - Fetal pituitary gland does indeed produce GH but: ➨ no evidence that GH is essential for fetal growth ➨ GH-deficient infants are normal size at birth ➨ GH-deficient infants of GH-deficient mothers have normal birth size - IGF-II is important during fetal development ➨ IGF-II production is stimulated by the placenta and is not GH dependent ➨ IGF-II continues to be produced in adulthood and may be involved in muscle growth Growth 23