Lecture 20: Thyroid Hormones Flashcards
what joins the two lobes of the thyroid gland
section of tissue called isthmus
what is the thyroid gland comprised of
lobules of spherical follicles filled with colloid
what type of cells make up the follicles present in thyroid lobules
follicular cells –> cuboidal epithelial cells
what is the primary constituent of colloid
thyroglobulin
what is incorporated into a thyroglobulin molecule
residues of amino acid tyrosine
what is the function of the C (parafollicular) cell
produces hormone calcitonin
where does thyroid hormone synthesis take place
in colloid
what molecule acts as a scaffold for thyroid hormone synthesis
thyroglobulin
what are the basic ingredients for thyroid hormone synthesis
tyrosine and iodine
which ingredient of thyroid hormone synthesis needs to be consumed in the diet
iodine
give examples of food that contains iodine
- sea vegetables
- iodised salt
- eggs
- cranberries
- seafood
consequence of low iodine in diet
hypothyroidism
outline how thyroxine (T4) and triiodothyronine (T3) are formed
- I + tyrosine = MIT
- MIT + I = DIT
- DIT + DIT = T4
- DIT + MIT = T3
explain how iodine gets into the follicle cell and then colloid in thyroid
- iodine reduced by digestion in stomach to iodide
- co-transported with Na+
- secondary active transport using energy from Na+/K+ ATPase pump
- 2 Na+ ions transported with 1 I-
- move through follicle cell by diffusion
- I- transported across apical membrane via I-/Cl- transporter into lumen (colloid)
how is T3/ T4 formed in the colloid
- iodide is oxidised back to iodine by hydrogen peroxide
- thyroid peroxidase (TPO) attaches iodines to tyrosine in thyroglobulin
- coupling of DIT/MIT to give T3 or T4
what is the use of radioactive iodine
- diagnostic, tracer, and therapeutic (causes cells to die in hyperthyroidism
which thyroid hormone is produced most in thyroid gland
T4 (80-90%)
which thyroid hormone is more biologically active
T3 - binds with greater affinity to nuclear receptors
how is T4 converted to T3
T4 needs to be deionised by deiodinase
what are the types of deiodinase and where do they come from
type 1 –> liver, kidney, thyroid, pituitary, heart
type 2 –> pituitary, brain, skeletal muscle, brown adipose
type 3 –> placenta, uterus, brain, kidney, liver, thyroid, fatal tissues
where does most systemic T3 come from
liver and kidney by type 1 deiodinase
which molecule is responsible inactivation of T3
type 3 deiodinase
how are thyroid hormones transported in plasma
- thyroid hormones are lipophilic transported by: --> thyroid binding globulin (TBG) --> thyroid binding pre albumin (TBPA) --> thyroid binding albumin (TBA)
- tiny % of thyroid hormone unbound in blood
which thyroid hormone being transported is biologically active
free unbound thyroid hormone
where are majority of thyroid receptors located
in nuclei of cells
how does thyroid hormone cause suppression or activation of genes in a cell
- binds to receptors in nucleus of a cell causing genomic effect
- translocation to hormone response element on DNA
- proteins produced after suppression/activation of genes
function of proteins after suppression/activation of genes by thyroid hormone
increase metabolism within cell therefore thyroid hormones increase basal metabolic rate
how do thyroid hormones increase ATP production
bind to receptors directly on mitochondria
describe the metabolic actions of thyroid hormones
- increased O2 consumption (required by proteins produced)
- increased BMR (basal metabolic rate)
- calorigenic effect –> thermogenic effect
- carbohydrate metabolism
- -> ^ absorption of glucose from GIT, ^ glycogenolysis, ^ gluconeogenesis
- lipid metabolism
- -> lipolysis…^ circulatiing FFA, ^ FFA oxidation, decrease cholesterol, ^ No. of LDL receptors
- protein metabolism
- -> prot. synthesis and breakdown
describe systemic effects of thyroid hormones
Heart
- -> ^ HR, CO, SBP and decrease DBP (sympathomimetic effect)
- -> ^ blood flow to skin
Lungs
–> ^ vent. rate
GIT
- -> ^ appetite
- -> ^ secretion digestive juices
- -> ^ GIT motility
Reproductive
–> essential for normal reproduction and lactation
MSK
- -> promotes normal body growth and maturation of skeleton
- -> promotes normal body function and development of muscles
NS
- -> promotes normal neuronal development in foetus and infant
- -> promotes normal neuronal function in adult (^ synaptic activity)
- -> ^ effects of SNS - sympathomimetic; up regulates B1 adrenergic receptors in heart
what effect does cold have on production of TRH in hypothalamus
+ve
what effect does stress have on production of TRH in hypothalamus
-ve –> prevents overstimulation of SNS
how does TSH act on thyroid gland
- ^ iodide trapping and binding (by ^ gene transcription of Na+/I- symporter)
- promotes thyroglobulin synthesis and secretion into colloid
- TPO synthesis
- stimulates T3 and T4 synthesis
- promotes colloid endocytosis into follicular cells
- ^ size and No. of follicular cells
- ^ blood flow at thyroid level
what do primary/secondary/tertiary levels of hypothyroidism refer to
1st - problem at thyroid (failure to respond to TSH)
2nd - problem at pituitary (w/ TSH); deficient TSH secretion –> thyroid atrophy (shrinking)
3rd - problem at hypothalamus (w/ TRH) –> deficient TSH secretion due to deficient TRH secretion
what is hypothyroidism
deficient production of thyroid hormone
name some causes of primary hypothyroidism
- thyroiditis e.g. Hashimoto’s disease or chronic lymphocytic thyroiditis (CLT)
- severe iodine deficiency
- severe deficiency of one or more synthesis enzymes
- removal or destruction of thyroid gland
name some consequences of primary hypothyroidism
- elevated TSH levels –> reduced -ve feedback
- thyroid enlarges –> goitre formation
how is congenital hypothyroidism diagnosed
blood test performed on all newborns (ESSENTIAL EARLY DIAGNOSIS)
describe developmental consequences of hypothyroidism in baby
- sometimes enlarged tongue
- unhappy
- difficulty feeding
- difficulty w/ GIT
describe developmental consequences of hypothyroidism in adult
- short
- impaired brain, bone and other development
- poor coordination
what happens if you don’t have a functional thyroid gland
thyroid hormone is replaced
name causes of hyperthyroidism / thyrotoxicosis
- autoimmune disease –> Grave’s disease
- thyroid adenoma
- TSH secreting adenoma
how does Grave’s disease cause hyperthyroidism
- autoantibodies stimulate thyroid gland
- bind to same receptors as TSH
- thyroid gland secrete excess T3 and T4
diagnostic factors of Grave’s disease
- very low TSH
- goitre
- exophthalmos
- retraction of upper eyelid
