Lecture 4 - endocrine control of growth

Question 1

Growth depends on growth hormone but is influenced by other factors:

Answer 1

Genetic
Diet
Freedom from chronic disease and stressful environmental conditions
Normal levels of growth-influencing hormones

Question 2

Prolonged stress-induced secretion of cortisol results in

Answer 2

Stunted growth: Anti-growth effects of cortisol
- Promoting protein breakdown
- Inhibiting growth of long bones
- Blocking secretion of growth hormone

Question 3

Normal levels of growth-influencing hormones
- must be present for GH to perform function

Answer 3

• Thyroid hormone
• sex hormones

Question 4

Gh is mostly secreted at

Answer 4

night

Question 5

GH secretion is regulated by 2

Answer 5

hypophysiotropic hormones

Question 6

GH secretion is regulated by which 2 hypophysiotropic hormones

Answer 6

GHRH and GHIH

Question 7

Hormones that take part in the secretion of GH

Answer 7

GHRH
GHIH = somatostatin
GH = somatotropin
IGF = somatomedin

Question 8

GH secretion is regulated by 2 hypophysiotropic hormones, GHRH and GHIH, how?

Answer 8

Both GHRH and GHIH act on the anterior pituitary somatotropes by binding with G-protein-coupled receptors linked to cAMP second messenger pathway: GHRH increasing cAMP and GHIH decreasing cAMP

Question 9

Question 10

Regulation of Growth Hormone Secretion

Answer 10

GH-somatotropin
GHIH- somatostatin
IGF-1- somatomedin

Question 11

Growth Hormone exerts metabolic effects not related to growth. How and whats the result?

Answer 11

Binds directly to target tissue: adipose tissue, skeletal muscle and liver
- decrease blood amino acid levels
- increased fatty acid levels in blood
- increased blood glucose levels; increase glucose output by liver

THUS: mobilize fat stores as major energy source while conserving glucose for glucose dependent tissue such as the brain, eg. fasting or when body’s energy needs exceed glucose stores

Question 12

GH primarily promotes growth indirectly by

Answer 12

stimulating liver’s production of somatomedins [Insulin-like growth factor (IGF-I)]

Question 13

Insulin-like growth factor (IGF-I)

Answer 13

Secreted in bones and soft tissues
which results in protein synthesis, cell division, and lengthening and thickening of bones

Question 14

IGF’s are produced in many tissues and result in certion actions

Answer 14

– endocrine, paracrine and autocrine actions

Question 15

IGF’s bind to receptor-enzyme

Answer 15

tyrosine-kinase pathway

Question 16

Major source of IGF-I IS THE _______. And the release is in response to ______

Answer 16

liver
GH

Question 17

IGF-I also produced by most other tissue (not released into blood)

Answer 17

– act in paracrine manner

Question 18

IGF production is controlled by number of factors other than GH:

Answer 18

Nutrition status:
Inadequate food intake and fasting - IGF-I, BUT + GH secretion

Age-related factors:
Dramatic + in circulating IGF-I with modest increase in GH at puberty

Tissue specific increases:
Sex hormones stimulate IGF-I in male reproductive organs (testes) and female uterus and ovaries.

Question 19

IGF-II

Answer 19

Not influenced by GH
Primarily important during fetal development
Role in adults unclear

Question 20

Growth hormone (GH) /IGF-I promote growth of soft tissue by stimulating

Answer 20

hyperplasia and hypertrophy

Question 21

Hyperplasia

Answer 21

Increasing number of cells
Stimulating cell division
Preventing apoptosis

Question 22

Hypertrophy

Answer 22

Increasing size of cells
Favoring protein synthesis
Inhibit protein degradation
Promote uptake of amino acids by cells – decreasing blood amino acids levels in process
Increases DNA and RNA synthesis
Increases incorporation of amino acids into new proteins at ribosomal level

Question 23

Bone growth

Answer 23

• Can be endochondral and linear
• in compact and trabecular bone

Question 24

Growth in thickness of bone:

Answer 24

= Endochondral bone growth:
Osteoblasts in periosteum
Osteocalcin & osteonectin – proteins which aid in deposition of calcified matrix

Question 25

Linear bone growth

Answer 25

– epiphyseal plate

Question 26

Bone growth is under the influence of

Answer 26

GH and IGFs without it = abnormal bone growth

Question 27

Long bone growth: Also influenced by steroid sex hormones

Answer 27

Puberty: Boys: Growth spurt of puberty - + androgen production Girls: Androgens from adrenal cortex: estrogens stimulate & inhibit linear growth Adolescents: sex hormones inactivate epiphyseal plate Adults: linear bone growth ceases; BUT bone are dynamic tissues – undergo continuous remodeling under control of hormones which regulated calcium metabolism in body

Question 28

36 year old professional body builder required emergency care for chest pain Lost 40 kg in 12 months Excessive urination, thirst & appetite Admitted using anabolic steroids for 15 years and artificial GH for past 3 years Took insulin a year after starting GH, but he stopped due to hypoglycaemia in gym Tests: inflammed liver, enlarged kidneys, very high blood sugar, dehydration, diabetes Treatment: intravenous fluids, gradually increasing insulin over few days Use of GH increases among athletes and bodybuilders – easy to buy on line, difficult to detect in screening tests – unlike anabolic steroids Question: What was the reason for taking insulin?

Answer 28

GH increases blood glucose levels, so took insulin to counteract effect

Question 29

Factors that influence GH secretion

Answer 29

Diurnal rhythm Exercise Stress Low blood glucose + in amino acids after high-protein meal Low blood fatty acids levels Ghrelin (appetite stimulator) – coordinate nutrient acquisition with growth

Question 30

Question 31

Question 32

Why aren’t adult tissues still respond to GH growth-promoting effects? Epiphyseal plates have closed, but why do soft tissue not continue to grow through hyperplasia and hypertrophy?

Answer 32

Speculation: GH secretion burst during deep sleep which is greatest in infancy and gradually decreases with age

Question 33

Growth hormone deficiency due to

Answer 33

pituitary defect or hypothalamic dysfunction

Question 34

Hyposecretion of GH in child is one cause of dwarfism

Answer 34

Retarded skeletal growth Poorly developed muscles (- muscle protein synthesis) Excess subcutaneous fat (- fat mobilization)

Question 35

Laron dwarfism

Answer 35

blood GH levels high abnormal GH receptors, tissue fail to respond to GH

Question 36

African pygmies

Answer 36

GH levels and tissue response adequate, BUT IGF’s are lacking

Question 37

Deficiency of GH in adults:

Answer 37

produces relatively few symptoms – GH maintains cardiac muscle mass (increased risk of heart failure)

Question 38

Growth hormone excess

Answer 38

Most often caused by tumor of GH-producing cells of anterior pituitary Symptoms depend on age of individual when abnormal secretion begins

Question 39

Gigantism

Answer 39

Caused by overproduction of GH in childhood before epiphyseal plates close

Question 40

Acromegaly

Answer 40

Occurs when GH hypersecretion occurs after adolescence