Thyroid Flashcards
Thyroid gland
Consists of:
Thyroid follicles where thyroid hormones are syntehsized
-composed of follicular cells arranges in a circular pattern
–simgle layer of epithelijm
–cells responsible for thyroid hormone syntehsis
Follicles filled with colloid
- intrafollicular fluid rich in thyroglobulin
- factory storage of thyroid hormones and components
Parafillicular cells (c cells)
-located between the thyroid follicles and produced the hormone calcitonin
Involved the calcium regulation
Thyroid hormones
Two molecules serve as precursors or raw materials: Tyrosine and Iodide
Tyrosin- part of thyroglobulin, a large tyrosine rich protein
- synthesized by follicular (epithelial) cells
- secreted into the follicle lumen or colloid
Iodide- obtained from diet as iodine and actively taken up from blood to thyroid epithelial cells
- iodine concerted to iodide in intestinal tract
- follicle cells uptake iodide through active transport
- -Na/I cotransporter
- -intracellular iodio concentration is 25-200x higher than outside of cell
Thyroid hormones: synthesis
First step in production oxidation of iodide ion to iodine
-thyroid peroxidase (TPO) located in the apical membrane oxidize iodide to iodine. Iodine then capable to combine directly with aa tyrosine
Second step, binding of iodine with the thyroglobulin molecule
-known as organification of the thyroglobulin
TPO
-provides iodine at the exact point in the cell where thyroglobulin is released
-iodine is then capable to combine directly with the aa tyrosine
TPO catalyses the fusion of two of these iodinated thyrosines
DIT + DIT = T4 or thyroxine
MIT + DIT =t3
T4 is the major hormone produced by the follicular cells
-only small amounts of T3 are produced
-major source of T3 is peripheral deiodination of T4 on target tissues
Thyroid hormones remains attached to thyroglobulin molecule and stored in the colloid until secretion
-this kind of storage is unique and allows the thyroid to have a large reserve of hormone
TPO action summary
Epithelial cell enzyme catalyzes squential reactions:
- iodide is oxidized to iodine
- iodination of tyrosine on thyroglobulin (organification of iodide)
- catalysis (peroxidase) of MIT and DIT to yield triiodothyronine (T3) ir thyroxine T4
Thyroid hormone: secretion
Follicular cells ingest (endocytosis) thyroglobulin with attached thyroid hormones (T4 and T3), DIT, MIT
-endosomes fuse with lysosomes
Hydrolytic enzymes digest thyroglobulin- T3 and 4 released
Free thyroid hormones diffuse out of the epithelial cells and into interstitial space and blood- thyroglobulin and I- recycled
Thyroid hormones: transport
Thyroid hormones are transported in plasma attached to proteins (>99%)
-thyroxine-binding globulin (TBG, binds majority of T3 and 4) transthyrein and albumin— produced by liver
A small amount is free in the circulation
-free T4 and small amount of free T3 diffuses into the target cells
-once free T4 has entered, most of it will be converted to T3 by iodothyronine deiodinases in the cytosol
Thyroid hormones: regulation
Hypothalamus-pituitary-thyroid axis
Hypothalamus produces thyrotropin-releasing hormone
Pituitary produces Thyroid-stimulating hormone
Thyroid stimulated by TSH to produce T3 and 4
T3 binds to transcription factor and causes transcription to mRNA
Deiodinases
In most vertebrates there are three types of tissue-specific enzymes that can deiodinate thyroid hormoens
Convert T4 to T3 in peripheral tissues
Thyroid hormones: actions
Thyroid hormones are the primary factors for the control of metabolism
-bind to nuclear receptors and initiates the transcription of mRNA
Increase the number of mitochondria and activity of mitochondria
Increase the basal metabolic rate of cells: weight loss in hyper/weight gain in hypo
Stimulate carbohydrate metabolism
Fat metabolism
Growth and development are influenced by thyroid hormone
Increase blood flow and cardiac output
Increase HR
Gi effects
Hypothyroidism
Decreased synthesis and secretion of thyroid hormones
Dogs
Commonly seen in cats following bilateral thyroidectomy as a result of hyperthyroidism
Types:
Primary: thyroid gland dysfunction (most common)
Secondary: pituitary gland dysfunction (TSH deficiency) is rare (pituitary tumors)
Tertiary: hypothalamic dysfunction (TRH deficiency) is rare or not described
Congenital: thyroid gland hyperplasia reported in foals as result of mares diet during pregnancy
Hyperthyroidism
Most common feline endocrine disorder
Rare in dogs
Overproduction of thyroid hormones
-thyroid adenoma or benign adenomatous hyperplasia accounts for approximately 95% of hyperthyroidism in cats
Thyroid carcinoma is most common cause of hyperthyroidism in dogs
