Endocrinology: Endocrine Control of Growth Flashcards
Define growth
Growth = the organised addition of new tissue that occurs normally in development.
Except for longitudinal growth, many of the processes involved continue to operate throughout life (e.g., tissue remodelling)
Factors that influence growth
- Genetics
- Nutrition
- Growth influencing hormones – growth hormone, thyroid hormone, somatomedins/IGFs, insulin, sex hormones
- Chronic stress and disease
What is growth hormone also known as?
Growth hormone, aka somatotropin; somatotropic hormone
Where is growth hormone produced? What type of hormone is it?
Polypeptide hormone produced in somatotrophs of anterior pituitary
How is secretion of growth hormone regualted?
Secretion regulated by GHRH and GHIH (somatostatin)
growth hormone releasing hormone and growth hormone inhibiting hormone
Growth hormone mechanisms of action
- Transported bound to growth hormone binding protein
- Targets many tissues where it influences fuel metabolism
- GH binding to enzyme-linked receptor produces activation of kinase cascade which ultimately alters gene transcription
- Overall effect is to use up fat stores and promote protein synthesis
Growth hormone secretion pattern
- Irregular pulses
- Largest bursts during deep sleep
- Pulse amplitude maximum at puberty, then declines
What is secretion of growth hormone stimulated by?
- GH-releasing hormone (GHRH)
- Oestrogens and androgens
- Decreased blood glucose
- Decreased blood fatty acids
- Exercise
- Excitement/ stress/ trauma
- Sleep
- Increase in amino acids
What is secretion of growth hormone inhibited by?
- GH-inhibiting hormone (GHIH; somatostatin)
- Somatomedins (-ve feedback)
- Obesity
- Increased blood glucose
- Increased blood fatty acids
- aging
Hypothalamus role in growth hormone secretion
Hypothalamus
- Growth hormone releasing hormone (GHRH) and somatostatin (GHIH) are produced
- GHRH stimulates release of growth hormone from the pituitary gland, somatostatin inhibits it
Pituitary gland and growth growth hormone
Synthesises and stores growth hormone
What happens once growth hormone is secreted?
Negative feedback
- Once growth hormone is secreted into the bloodstream, it exerts is effects on target tissues (liver, adipose tissue, skeletal muscle)
- It promotes growth, metabolism and other physiological processes
- Regulates its own secretion: high levels of GH in blood inhibits release of GHRH, stimulates release of somatostatin, and vice versa
What are somatomedins?
Somatomedins (insulin-like growth factors = IGF)
Peptide hormones that have strong mitogenic properties (encourage cell division)
Where are IGFs produced?
Insulin-like growth factors
IGFs are produced primarily in the liver, but also in most other tissues (where it has an autocrine/ paracrine effect)
Types of IGF
Insulin-like growth factors
There are two types (IGF-1, IGF-2)
IGF-1 effects most cells in the body where it stimulates cell growth, multiplication and inhibits apoptosis (programmed cell death)
IGF-2 is a growth promoting hormone during gestation
Most important IGF
Somatomedin C (IGF-1) is the most important IGF: pygmies and some dwarfs lack IGF-1
What do pygmies and some dwarfs lack?
IGF-1
Bone growth via IGF-1
Bone growth: growth hormone (via IGF-1)
- Stimulates proliferation of epiphyseal cartilage
- Increases conversion of cartilage to new bone (increasing length of long bones and skeleton until epiphyses of long bones fuse with shafts)
- Increased proliferation of periosteal osteoblasts (increasing bone thickness)
- Increase in bone remodelling
Metabolic actions of growth hormone
- Increase fat breakdown into fatty acids (lipolysis)
- Decrease glucose uptake by muscles
- Decrease sensitivity to insulin
- Increased blood glucose
Target cells of growth hormone
Unlike other anterior pituitary hormones, growth hormone doesn’t function through a target gland as such, it exerts its effects on almost all tissues of the body.
Additional factors (besides growth hormone) that influence foetal growth
- Promoted by placental hormones (GH-independent)
- Birth size determined mainly by genetics and environment
- Neurological growth maximum in late intrauterine and early postnatal life
Factors that affect postnatal growth
- Largely determined by GH (+ somatomedins, T3 and T4, insulin, androgens, and estrogens)
- Increase in GH during puberty
- Increase in androgens (from testes and adrenal gland) contribute to pubertal growth spurt by increasing protein synthesis and bone growth
Hormones that influence growth (besides growth hormone)
- Thyroid hormones: permissive for GH synthesis, release (via increase GHRH receptor) and actions (increase GH receptor, increase IGF-1, increase IGF-1 receptor). Children with hypothyroid conditions have their growth severely stunted, however, hypersecretion of thyroid hormone doesn’t stimulate excess growth
- Insulin: required for optimal effects of growth hormone (IGF-1 is low in diabetes). Growth hormone fails to cause growth in an animal that lacks a pancreas or if carbohydrate is excluded from the diet-lack of energy source and attenuated transport of amino acids into cells
- Gonadal hormone: during puberty estrogens increase GH pulse amplitude and frequency; also play a role in closure of epiphyseal plates – terminating growth in both sexes. Andogens involved in the pubertal growth spurt by stimulating protein synthesis (increase muscle mass)
- Glucocorticoids: permissive for optimal growth; increase GHRH receptor and GH synthesis. High concentrations inhibit growth (e.g., pharmacological doses to treat asthma and inflammations)
Effects of hypersecretion of growth hormone
If in childhood, then rapid, excessive growth; body remains in proportion (gigantism)
If after adolescence, then bones don’t lengthen but will thicken; increased soft tissue formation (acromegaly)
Cause, affect and treatment of gigantism
o Cause: pituitary adenoma; pituitary hyperplasia
o Effect: rapid growth of all tissues, hyperglycaemia (leading to diabetes mellitus in 10%)
o Treatment: somatostatin analogs, surgery
Cause effect and treatment of acromegaly
o Cause: pituitary tumour after adolescence
o Effect: bones grow in thickness not length (cranium, nose, supraorbital ridges, mandible, vertebrae). Enlargement of hands and feet, elongation of ribs (barrel-chested appearance). Enlarged tongue, liver, kidneys, heart. Diabetes
o Treatment: somatostatin analogs, surgery
Cause, effects and treatment of growth hormone deficiency
Pituitary dwarfism
- Cause: congenital defect, pituitary tumour or trauma causing panhypopituitarism (decrease secretion of all anterior pituitary hormones) or isolated GH (or IGF-1) deficiency
- Effect: slow and reduced growth (to ~4ft). proportional appearance. Craniofacial dysmorphisms include frontal bossing, midfacial hypoplasia and micrognathia. If panhypopituitarism, will also have hypothyroidism, hypogonadism and low glucocorticoids
- Treatment: human GH +/- thyroxine, cortisol
Symptoms of acromegaly, related to the oral cavity
Acromegaly and oral health: dental professionals may be the first healthcare providers to note early symptoms and signs of acromegaly (and gigantism)
- Enlarged lips and tongue (macroglossia)
- Increased spaces between teeth
- Mandible growth after puberty: class 3 malocclusion; prognathism
- Accelerated tooth eruption in children
- Facial features become broader and thickened
- Maxillary sinuses are larger
- Hyperglycaemia/ diabetes mellitus: increased risk of gingivitis and periodontal disease
Are all growth abnormalities directly related to aberrant growth hormone secretions? Give examples
No
- Laron dwarfism is characterised by abnormal GH receptors
- African pygmies have IGF-1 (or receptor) deficiency
- Primordial dwarfism doesn’t respond to GH treatments (due to mutation of pericentrin gene causing abnormal cell division)
- Cartilage-hair hypoplasia is due to mutations in the ribonuclease mitochondrial RNA-processing (RMRP) gene
