Endocrine 3 Flashcards
4 factors that influence growth apart form growth hormone
- Genetic determination
- An adequate diet
- Freedom from chronic disease and stressful environment
- Normal levels of growth-influencing hormones
Stressful environment influencing growth
Stunted growth from stress induced secretion of cortisol –over a prolonged period of time.
- Cortisol can promote protein breakdown, inhibiting growth of long bones and block the secretion of GH.
Growth influencing hormones role
In addition to GH, hormones including thyroid hormone, insulin and the sex hormones play secondary roles in promoting growth
2 major regulators of growth
- Growth hormone
* Somatomedins (IGFs; insulin growth factors)
Other growth influencing hormones x 4
- Oestrogens / Testosterone
- Insulin
- Thyroid hormones
- Calcitonin, PTH and Vitamin D
Other growth FACTORS
- Epidermal Growth Factor
- Platelet Derived Growth Factor
- Nerve Growth Factor
- Fibroblast Growth Factor
Function of Platelet Derived Growth Factor
Stimulates fibroblasts and glial cell growth
Function of nerve growth factor
Neuronal survival and synaptic out-growth
Function of fibroblast growth factor
Stimulates bone cell proliferation and collagen synthesis
What is epidermal growth factor?
Polypeptide with mitogenic activity
What is growth hormone also called?
Somatotropin
Where is GH encoded?
On chromosome 17
Mol wt of GH
20kDa
GH - what peptide?
Peptide hormone 191 amino acid
Release of GH
- not continuous
* different factors responsible for growth at different periods
Fetal growth (promoted, GH role)
- promoted by placenta hormones
* GH plays no role in fetal growth
When does the postnatal growth spurt occur?
First two years of life
Hormones in puberty growth spurt
- Male: Androgens (testes) promote growth
* Female: Androgens (adrenal glands, less potent) promote growth
2 growth periods of rapid growth in children
A postnatal growth spurt up to the age of 2 and a pubertal growth spurt during adolescence
Puberty age in girls
11
Puberty age in boys
13
What hormones promotes sharp increase in height in boys
Testosterone
What is most likely involved in female growth spurt?
Androgens from the adrenal cortex
What do both testosterone and oestrogen act on and why?
On bone to halt its further growth so that full height is attained at the end of adolescence.
Type of release in GH release
Pulsed release
GH pulsed release
─ released from anterior pituitary in several bursts
─ high morning before awakening, low in day
─ secretion stimulated during deep sleep
─ rhythm linked to sleep-wake not light/dark
─ surges in first 2 hr sleep at night
Number / magnitude of GH release in age
- high in puberty
- low in adults
- absent at 50yr+
Age-related decrease in GH release causes
- change in muscle:fat ratio
- decreased bone density
- GH sold as “anti-ageing” therapy? (but may actually speed ageing)……..
What are GHRH (growth hormone releasing hormone) and somatostatin produced by?
Hypothalamic neurons
GHRP receptor type
a 7 transmembrane domain G-protein coupled receptor
What does GHRH stimulate?
GH synthesis and secretion
What is GH initiated by?
By bursting secretion of GHRH
What is GH terminated by?
Somatostatin
What does injection of GH into animals cause? x 6
- increases glucose levels in blood
- promotes protein synthesis
- promotes lipolysis in adipocytes
- promotes bone growth
- results in erythropoesis
- has anti-insulin activity
Long term metabolic effects of GH x 4
Carbohydrates - increases glucose levels in blood Proteins Synthesis - increases tissue amino acid uptake Lipids (Lipolysis) - increases free fatty acids in blood Stimulates Growth - stimulates IGF production
What does GH release?
IGF-1
What does GH stimulate? x 3
- Liver production of somatomedins (insulin-like growth factor; IGF-1)
– Acts on bone & soft tissues to promote growth
– Protein synthesis, cell division (of chondrocytes), lengthening, thickening of bones
Metabolic effects of GH
– increases fatty acid levels in blood (by breakdown of fat)
– increases blood glucose levels (by decrease of glucose uptake by muscles)
Hypothalamus diagram for GH
What does GH mediate actions via?
IGFs
Why does GH stimulate the liver?
To produce IGFs
What are IGFs (insulin-like growth factors) structurally related to?
Insulin
What does IGF stimulate?
- Bone and soft tissue growth
- Hyperplasia: cell proliferation
- Hypertrophy: increasing the size of cells
What does IGF prevent?
Apoptosis
Mice genetically lacking GH are …
Dwarfed
x 3 GH diseases
- Pituitary Gigantism
- Acromegaly
- Dwarfism
Pituitary giantism cause
GH excess caused by tumour cells of anterior pituitary
Pituitary giantism name in adults
Acromegaly
What causes acromegaly
GH hypersecretion after adolescence
What cause GH hypersecretion in acromegaly?
Benign tumors (adenomas) in pituitary gland
Feature of acromegaly x 5
– thickening of bones – coarsened facial features – soft tissue swelling (hands and feet) – heart failure – vision loss (compressed optic chiasm)
Medication reduce GH secretion/tumor x 3
– Bromocriptine (DA receptor agonist)
– somatostatin, to stop GH production
– GH receptor antagonists are emerging
4 types of dwarfism
- GH deficiency
- Hereditary
- Laron dwarf
- African Pygmy
GH deficiency dwarfism
- low GH
* treated by replacing with GH
Hereditary dwarfism cause
Low GHRH
Laron dwarf cause
Defective GH receptor
African pygmy cause
Defective IGF1 receptor
Feedback loop of GH
NB - Metabolic effects of GH not related to growth
Increases fatty acid levels in the blood by enhancing breakdown of triglyceride fat stored in adipose tissue.
Increases blood glucose by decreasing glucose uptake by muscles and increasing glucose output by the liver– muscle use mobilised fatty acids as fuel instead of glucose.
Overall metabolic effect of GH
mobilise fat stores as a major energy substrate while conserving glucose for glucose dependent tissues such as brain.
Hypothyroid children growth affect
Growth severely stunted.
Hypersecretion growth affect
Does not affect growth.
Insulin function
Growth promoter.
Promotes protein synthesis.
Insulin deficiency growth consequence
Blocks growth
Hyperinsulinism
Spurs excessive growth
Thyroid hormone permissive role
Permissive role in skeletal growth; the actions of GH only manifest when sufficient TH is present.
Thyroid hormone need
Necessary for growth BUT not directly responsible for promoting growth
Other hormones responsible for growth
Androgens
Oestrogens
Androgens function
- Pubertal growth spurt, stimulate protein synthesis in many organs.
- Stimulate linear growth
- Promote weight gain
- Increase muscle mass
Whats the most potent androgen?
Testosterone
Testosterone function
Promotes a sharp increase in height in adolescent boys.
In the absence of GH, what is the effect of androgens?
Virtually no effect on body growth
Oestrogens growth function
Thought to contribute to the pubertal growth spurt in females but its exact role is uncertain.
Location of thyroid gland
Located on the front of upper part of trachea
What does the thyroid gland develop from?
Epithelial outgrowth of tongue
What does the thyroid gland develop from?
Epithelial outgrowth of tongue
Major secretory cells of thyroid gland
Follicular cells, arranged in hollow spheres – functional unit is a follicle
Follicles appearance and structure
Appear as rings consisting of a single layer of follicular cells enclosing an inner lumen filled with colloid
Colloid function
Serves as an extracellular storage site for TH.
Name a major constituent of colloid
Large glycoprotein molecule known as thyroglobulin (Tg) – incorporated into TH during their synthesis.
x 3 Types of thyroid hormones
- T3 (Triiodotyronine) - in follicles
- T4 (Thyroxine) - in follicles
- Calcitonin by C cells
Calcitonin role
Role in Calcium metabolism not related to T3/T4
Function of T3 and T4
- Accelerate metabolism
* Increase carbohydrate, fat and protein turnover
T3 and T4, what type of hormone base
Tyrosine-based hormones
T3 and T4 structure
T3 has 3 iodine atoms, T4 contains 4
T3 and T4 compare effectiveness
T3 more effective, but T4 more abundant
What are levels of T3 and T4 controlled by?
Anterior pituitary TSH
Transport of T3, T4
In blood, bound to thyroxine-binding globulin (TBG)
T3 and T4 produced
Made by follicular cells when iodide available
Hoe is iodide absorbed?
Absorbed from blood to thyroid follicles
Synthesis, Storage and secretion of TH
x 6 Effects of thyroid glands
- Main determinant of basal metabolic rate
- Influences synthesis and degradation of carbohydrate, fat and protein
- Increases target cell responsiveness to catecholamines
- Increases heart rate and force of contraction
- Essential for normal growth
- Plays crucial role in normal development of the nervous system
Feedback loops of thyroid hormone
Low iodine uptake disease
Goiter
Goiter disease
dietary iodide insufficiency
- no T3/T4 made
- thyroid cell proliferation
- iodide uptake increases
- normal human thyroid gland of 25g may grow to 250 g during goiter
Thyroid autoimmune disease
Hashimoto’s
What happens in hashimotos?
Autoantibodies destroy thyroid follicular cells
Hypothyroidism infant disease
Cretinism
Cretinism ‘symptoms’
- stunted growth
- lack of bone formation
- skeletal abnormalities
- severe mental retardation
- Protruding tongue
Hypothyroidism cause
- Primary failure of the thyroid gland itself
Secondary to a deficit of TRH, TSH or both - Inadequate dietary supply of iodide
Hypothyroidism in older children adult disease
Myxedema
Clinical features of myxedema
- Generalised fatigue
- Mental slugglishness
- Slow speech
- Cold intolerance
- Overweight
- Shortness of breath
- Constipation
- Decreased sweating
- Cool and pale skin
- Generalized edema
- Enlargement of tongue
- Deepened voice
Hyperthyroidism symtoms
- high metabolic rate
- protruding eyes
- hyperactivity, insomnia
- heat sensitivity, weight loss, always hot
Hyperthyroidism disease
Grave’s disease
What is Grave’s disease
Autoimmune (TSH mimicked by autoantibodies – also known as thyroid stimulating immunoglobulin (TSI))
Grave’s disease treatments
– Beta blockers help some symptoms
– Anti-thyroid medications
– Radioactive iodine treatment destroys overactive thyroid cells
– Surgery thyroidectomy
Cause of hypothyroidism
- Primary failure of the thyroid gland
- Secondary to hypothalamic or anterior pituitary failure
- Lack of dietary iodine
Plasma concentrations of relevant hormones in primary failure of the thyroid gland
↓T3 and T4, ↑ TSH
Plasma concentrations of relevant hormones in secondary to hypothalamic or anterior pituitary failure
↓T3 and T4, ↑ TRH and/or ↓ TSH
Hypothyroidism - Plasma concentrations of relevant hormones in lack of dietary iodine
↓T3 and T4, ↑ TSH
x 3 Causes of hyperthyroidism
- Abnormal presence of thyroid-stimulating immunoglobulin (TSI) (Grave’s disease)
- Secondary to excess hypothalamic or anterior pituitary secretion
- Hypersecreting thyroid tumor
Hyperthyroidism - Plasma concentrations of relevant hormones in abnormal presence of thyroid-stimulating immunoglobulin (TSI) (Grave’s disease)
↑ T3 and T4,↓ TSH
Hyperthyroidism - Plasma concentrations of relevant hormones in secondary to excess hypothalamic or anterior pituitary secretion
↑ T3 and T4, ↑ TRH and/ or TSH
Hyperthyroidism - Plasma concentrations of relevant hormones in hypersecreting thyroid tumour
↑ T3 and T4,↓ TSH
What disfunction cause of hyper and hypothyroidism doesn’t have goiter?
- Hypersecreting thyroid tumour
- Secondary to hypothalamic or anterior pituitary failure
