Thyroid Flashcards
Storage form of TH
- Associated with thyroglobulin
- In the colloid
Parafollicular cells
- “C” cells
- Site of calcitonin synthesis/release
Thyroid hormone synthesis
- Precursor is tyrosine
- Synthesized on thyroglobulin and require iodide
- Preferential synthesis of T4
- Reverse T3 produced–biologically inactive
Significance of iodide
- Most stored in the thyroid gland associated with thyroglobulin
- Concentrated by a specific transport protein (Na/I symporter) that uses inwardly directed Na gradient as a driving force
- Thyroid has some capacity to autoregulate the transport of iodide
Synthesis of thyroid hormone
- Synthesized and stored by follicular epithelial cells
- TG produced in ER, packaged in golgi, exocytosed into lumen of follicle
- Iodide enters thyrocyte via basolateral Na/I cotransporters. Exits via apical side into the lumen by I/Cl antiporters
- In follicular lumen I oxidized to iodine by thyroid peroxidase and substituted for H on the benzene ring of tyrosine
- One iodine binding forms MIT and two binding forms DIT (organification)
- Two DIT form T4, one DIT and one MIT forms T3
- Mature TG endocytosed back into follicular cell to be stored as colloid
- Colloid proteolysis stimulated by TSH
Thyroid binding globulin
- Binds TH (70%)
- Transthyretin and albumin can also bind TH
- Small amount circulates freely
T4 metabolism
- Generates T3 and reverse T3
- Metabolized through the action of 5’ peripheral deiodinases
- T3 more potent and biologically active. T4 often referred to as a prohormone.
Treatment of hypothyroidism
- Usually use T4
- More stable, longer half life
TH entry into cells and transcriptional effects
- Typically TR heterodimerizes with RXR to regulate genes containing TREs
- 5’/3’ monodeoiodinase removes the 5’ iodine coverting T4 to T3.
Thyroid hormone action
- Increase metabolic rate and O2 consumption
- THs act synergistically with GH and somatomedins to promote bone formation
- Promote ossification and fusion of bone plates
- In hypothyroidism excessive throxine can lead to bone loss
Cretinism
- Mental and growth retardation resulting from TH deficiency in infants
- Growth retardation can be attenuated with T4
- Mental retardation can only be attenuated if treatment started early
TH effect on BMR
- Hypo: decrease BMR
- Hyper: Increase BMR
TH effects on carbohydrate metabolism
- Hypo: decrease gluconeogenesis, decrease glycogenolysis, normal serum glucose
- Hyper: increase gluconeogenesis, increase glycogenolysis, normal serum glucose
TH effects on protein metabolism
- Hypo: decrease synthesis, decrease proteolysis
- Hyper: increases synthesis, increase proteolysis, muscle wasting
TH effects on lipid metabolism
- Hypo: decrease lipogenesis, decrease lipolysis, increased serum cholesterol
- Hyper: increased lipgenesis, increased lipolysis, decreased serum cholesterol
TH effects on ANS
- Hypo: normal levels of serum catecholamines
- Hyper: increased expression of B adrenoceptors (increased sensitivity to catecholamines
TRH stimulation of TSH
- Activates GPCR linked to PLC
- IP3 generated and intracellular Ca mobilized
TSH stimulation of TH
- GPCR activated linked to AC
- Increased cAMP
Dopamine and somatostatin effect on TSH
-Inhibitory effects
