Lecture 4 - endocrine control of growth Flashcards
Growth depends on growth hormone but is influenced by other factors:
Genetic
Diet
Freedom from chronic disease and stressful environmental conditions
Normal levels of growth-influencing hormones
Prolonged stress-induced secretion of cortisol results in
Stunted growth: Anti-growth effects of cortisol
- Promoting protein breakdown
- Inhibiting growth of long bones
- Blocking secretion of growth hormone
Normal levels of growth-influencing hormones
- must be present for GH to perform function
- Thyroid hormone
- sex hormones
Gh is mostly secreted at
night
GH secretion is regulated by 2
hypophysiotropic hormones
GH secretion is regulated by which 2 hypophysiotropic hormones
GHRH and GHIH
Hormones that take part in the secretion of GH
GHRH
GHIH = somatostatin
GH = somatotropin
IGF = somatomedin
GH secretion is regulated by 2 hypophysiotropic hormones, GHRH and GHIH, how?
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
Regulation of Growth Hormone Secretion
GH-somatotropin
GHIH- somatostatin
IGF-1- somatomedin
Growth Hormone exerts metabolic effects not related to growth. How and whats the result?
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
GH primarily promotes growth indirectly by
stimulating liver’s production of somatomedins [Insulin-like growth factor (IGF-I)]
Insulin-like growth factor (IGF-I)
Secreted in bones and soft tissues
which results in protein synthesis, cell division, and lengthening and thickening of bones
IGF’s are produced in many tissues and result in certion actions
– endocrine, paracrine and autocrine actions
IGF’s bind to receptor-enzyme
tyrosine-kinase pathway
Major source of IGF-I IS THE _______. And the release is in response to ______
liver
GH
IGF-I also produced by most other tissue (not released into blood)
– act in paracrine manner
IGF production is controlled by number of factors other than GH:
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.
IGF-II
Not influenced by GH
Primarily important during fetal development
Role in adults unclear
Growth hormone (GH) /IGF-I promote growth of soft tissue by stimulating
hyperplasia and hypertrophy
Hyperplasia
Increasing number of cells
Stimulating cell division
Preventing apoptosis
Hypertrophy
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
Bone growth
- Can be endochondral and linear
- in compact and trabecular bone
Growth in thickness of bone:
= Endochondral bone growth:
Osteoblasts in periosteum
Osteocalcin & osteonectin – proteins which aid in deposition of calcified matrix
Linear bone growth
– epiphyseal plate
Bone growth is under the influence of
GH and IGFs
without it = abnormal bone growth
Long bone growth: Also influenced by steroid sex hormones
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
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?
GH increases blood glucose levels, so took insulin to counteract effect
Factors that influence GH secretion
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
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?
Speculation: GH secretion burst during deep sleep which is greatest in infancy and gradually decreases with age
Growth hormone deficiency due to
pituitary defect or hypothalamic dysfunction
Hyposecretion of GH in child is one cause of dwarfism
Retarded skeletal growth
Poorly developed muscles (- muscle protein synthesis)
Excess subcutaneous fat (- fat mobilization)
Laron dwarfism
blood GH levels high
abnormal GH receptors, tissue fail to respond to GH
African pygmies
GH levels and tissue response adequate, BUT IGF’s are lacking
Deficiency of GH in adults:
produces relatively few symptoms – GH maintains cardiac muscle mass (increased risk of heart failure)
Growth hormone excess
Most often caused by tumor of GH-producing cells of anterior pituitary
Symptoms depend on age of individual when abnormal secretion begins
Gigantism
Caused by overproduction of GH in childhood before epiphyseal plates close
Acromegaly
Occurs when GH hypersecretion occurs after adolescence
