Thyroid Hormones Flashcards
Hypothalamic TRH > Pituitary TSH > Thyroid gland produces thyroxin (T4) and triiodothyronine (T3)
Both T4 and T3 have the effect of _____, adjusted to alteration in ____, ___, ___, ___
T4 & T3 increase O2 consumption & metabolism
Adjusted in alteration in heat production, energy need, caloric supply, and environmental temperature
Describe the structure of a follicle.
Cuboidal endocrine cells surrounded by basement membrane forms single-layered circular follicles, the lumina of which contain thyroid hormones stored as colloid material
Thyroid gland also contains ___ that secrete ___.
parafollicular / C - cells
Secretes calcitonin
The stimulation of thyroid by ___ causes follicular cells to become more active at what?
TSH –> follicular cells become more active at
- Iodine uptake
- TH production
Iodothyronines
Secretory products of the thyroid glands
Iodine incorporated into 2 tyrosines
The major secretory product / iodothyronine of thyroid glands is ___, also known as ___.
3, 5, 3, 5 tetraiodothyronine AKA thyroxin (T4)
Functions largely as a circulating prohormone
The minor iodothyronine secreted is ___ AKA ___, which functions to ___
3, 5, 3 triiodothyronine AKA triiodothyronine (T3)
Provides almsot all thyroid hormone activity in target cells; produced in various tissues from the circulating prohormone T4
When less thyrhoid hormone action is needed, what happens to prohormone T4?
It’s turned into revers T3 (rT3), which is inactive and has unknown hormonal action
Thyroid hormone synthesis steps
-
UPTAKE AND CONC OF IODIDE in the gland
- Actively transported via Na-I cotransporter
- Iodide trap: process that maintains [iodide]gland >> [iodide]plasma
-
OXIDATION & INCORPORATION OF IODIDE
- Thyroid peroxidase incorporates iodide in Tyr of thyroglobulin –> monoiodotyrosine (MIT) and diodotyrosine (DIT)
-
COUPLING OF 2 IODINATED TYROSINES
-
Thyroid peroxidase couples
- two DITs –> T4
- MIT + DIT –> T3
- T4:T3 is usually 10:1, but restricted iodide availability leads to increased T3 formation
-
Thyroid peroxidase couples
Thyroid peroxidase
Uses H2O2 to oxidize iodine
Iodinates the tyrosines on thyroglobulin (protein w the Tyrs)
Thyroid hormones within ___ are cleaved by ____ and go through the basement membrane to enter the capillary blood.
Thyroglobulin cleaved by lysosomal enzymes to release T3 & T4, which will go through the basement membrane, leave the cells and enter into the capillary blood.
Deiodinase
The MIT and DIT molecules are rapidly deiodinated by enzyme deiodinase and iodide is reutilized for new hormone synthesis.
Where are iodinated thyroglobulins store?
How do they get transferred into endocrine cells?
Do they leave the endocrine cell?
Stored as colloid in follicle
Transferred from lumen of follicle into endocrine cells by endocytosis, but intact thyroglobulin doesn’t leave the cell.
Wha treactions occur within the endocrine cell?
Iodide traps
Thyroglobin synthesis
What reactions occur at the interface between the cell membrane and the colloid?
Iodination rxn
Coupling rxn
What reactions occur after thyroglobulin’s reabsorption from the colloid?
Cleavage by lysosomal enzymes to release T3 & T4
–> secretion of T3 & T4
Thiouracil drugs
Blocks enzyme peroxidase to treat thyroid hyperfunction
Iodide itself can be used to treat ___thyroidism
hyperthyroidism
Negative feedback of thyroid hormones
T4 & T3 inhibit synthesis of both TSH & TRH
T3 block TRH’s effect and suppresses its release
TRH or TSH:
Which is a tripeptide?
Which is a glycoprotein?
TRH = tripeptide
TSH = glycoprotein composed of two peptide subunits
Synthesis & action of TRH
Cut from a precursor tetrapeptide to a tripeptide TRH
- TRH binds its own receptor
- Increases in Ca2+ and IP3 –> stimulate release of TSH from anterior pituitary
- Downregualtes/desensitizes its own receptor
TSH / Thyrotropin functions
Stimulates all aspects of metabolism & growth of thyroid cells as well as
- iodide trapping
- thyroid hormone synthesis & secretion
- colloidal endocytosis
Iodide deficiency has what impact on TSH secretion?
Increases TSH secretion because thyroid hormone isn’t being synthesized
Goiter
enlarged thyroid gland due to TSH hypersecretion
Ex) from iodide deficiency -> cant make thyroid hormone ->increase TSH
What inhibits TSH secretion?
- T3 suppresses TSH release; represses TSH gene expression; downregulates TSH receptors
- Dopamine
- Somatostatin
- Cortisol
- Growth hormone
T4 and T3 are bound to what proteins while circulating?
- Thyroxin-binding globulin (TBG) binds ~20% of T4 and T3
- Transthyretin (thryoxin-binding parvalbumin)
- albumin
The __rity of total T4 and T3 are in the free state
MINORITY
What is the function of TBG & transthyretin?
To create a circulating reservoir of T4 –> provides buffering capacity against cute changes in thyroid gland function
Sustianed changes in the daily T4 supply from thyroid disease can lead to
sustained changes in both the bound and free reactions
Acute hepatic disease, pregnancies, estrogen therapy, or kidney disease can change ___ levels, which will disturb the ratio of free to bound T4
serum TBG level
Thyroid hormone replacement therapy is carried out with which thyrhoid hormone?
T4 (less hormonally active, but can be converted to T3 or rT3)
5 monodeiodinase
T4 –> T3
major target tissues of thyroid hormone
liver
kidney
skeletal muscle
T4 and T3 enter target cells by ___ then
energy-depenent transport
Then most of the T4 is converted to T3 and both T4&T3 are transported to the nucleus to affect transcription.
T3 binds nuclear receptors w greater affinity
Physiological effects of thyroid hormone
- Increased basal metabolic rate & general catabolic state
- Thermogenesis
- Increased O2 consumption
- Increases kidney size, renal plasma flow, GFR, and tubule transport
- Increases cardiac SV, HR, systolic BP
- Decreased diastolic BP
- CNS development
- Increased skeletal growth
- Regulates reproductive function
How does TH increase O2 consumption?
Stimualtes Na,K-ATPase, so ADP increases
–> increased mitochondrial O2 uptake
Rate of O2 consumption can be used to classify hypo (150mL/min), euthyroid (250mL/min), and hyperthyroid states (400mL/min)
Hyperthyroidism clinical features
Tx: B-adrenergic antagonists
Thyroid hormone causes increased ____, which shortens diastole, thereby increasing heart rate
sarcolemal uptake of Ca2+ shortens idastole
Causes of hyperthryoidism
Graves: autoimmune; antibody binds TSH receptors and mimics TSH
Neoplasm of thyroid
Thyroid inflammation; Excess TSH, ingestion of excess T3 & T4 ; High iodide
Tx of hyper thyroidism
Short-term iodine excess
Treatment with thiouracil for 18 months to block TH synthesis
Ablation of thyroid tissues via radioactive iodine or surgery
Hypothyroidism
