thyroid function Flashcards
overview of HPT axis (5)
- TRH synthesized in parvo neurons of PVN and released in ant. pituitary
- TRH binds to receptors on thyrotrophs
- stimulation and release of TSH
- TSH stimulates thyroid gland to increase synthesis of T3 and T4
- T3 and T4 inhibit secretion of TRH and TSH by negative feedback
hypothalamic pituitary connections: where does arterial (1) and venous (1) blood go in the HP axis and through which vessels does it pass through
arterial blood: passes through hypothalamic artery directly to hypothalamus
venous blood: passes through superior hypophyseal artery to the pituitary
how is TRH synthesized (2)
- synthesized as a large pre-pro-TRH protein in hypothalamus and several tissues
- only parvo neurons in PVN project to ME
major driver of T4 synthesis
TRH
negative regulator of TRH gene expression
T3
T3 increases expression of…
TRH peptidase at the nerve ending
effects of TRH on TSH-producing cells (3)
- stimulates secretion of preformed TSH
- stimulates synthesis of new TSH
- critical for normal glycosylation of TSH at post-translational level
why does pituitary TSH have low biological activity
because it isn’t glycosylated
roles of TRH at genomic and non-genomic levels
genomic -> binds thyrotrophs and acts on TSH gene/TSH mRNA (positive regulator)
non-genomic -> glycosylation of TSH at the pituitary level (post-translational effect)
roles of T3 at genomic and non-genomic levels at (a) hypothalamic level and (b) pituitary level
(a) genomic -> negative regulation of TRH secretion
non-genomic -> increases TRH peptidase (inactivates TRH) (post-translational)
(b) genomic -> downregulates expression of TSH gene/TSH mRNA
non-genomic -> alters glycosylation of TSH (post-translational) to inactivate it
what is the active thyroid hormone and what is the prehormone
active -> T3
prehormone -> T4
what kind of cell are thyrotrophs
basophilic
what type of relationship do TSH and TH have
negative inverse relationship -> the more TSH, the less TH; the more TH, the less TSH
glycoproteins (4)
- FSH
- LH
- CG
- TSH
what structural aspect is common to all glycoproteins
alpha chain
what determines receptor specificity (glycoproteins)
beta chain
structurally, what inactivates TSH
separation of alpha and beta chains
structure of TSH
glycoprotein with 2 chains (alpha and beta) with a CHO moiety (glycosylation) that is essential for biological activity
peak of TSH
night
temporal aspects of TSH secretion (2)
- circadian
- pulsatile
relationship bw TH receptor occupancy and TSH
- the more TSH, the less TH receptor occupancy
- the less TSH, the more TH receptor occupancy (because more TH)
levels of (a) T3(T3); (b) T3(T4); (c) T4 in liver
(a) mostly T3(T3) bound to receptors
(b) small amounts of T3(T4)
(c) minimal amounts of T4
levels of (a) T3(T3); (b) T3(T4); (c) T4 in anterior pituitary
(a) same levels as other tissues
(b) much higher receptor occupancy of T3(T4)
(c) small amounts
why is the receptor occupancy rate in anterior pituitary > 90% for T3(T4)
anterior pituitary has mechanism to convert T4 into T3 within the thyrotrophs
where does D2 convert T4 to T3
in the pituitary
relationship between TSH suppression and T3
linear relationship (more T3, more suppression)
what is needed to keep TSH levels normal
high level of receptor occupancy
what contributes to a large fraction of nuclear T3 in thyrotrophs
T4
anatomy of thyroid gland (4)
- thyroid cells organized in follicles
- follicles contain colloid, which contain thyroglobulin
- TH is synthesized and stored in thyroglobulin (until stimulated by TSH)
- C cells are found between follicles and produce calcitonin
structural difference bw T3 and T4
T4 has an extra iodine atom
synthesis and storage of thyroglobulin
produced in thyrocytes and stored in follicles in thyroid gland
why don’t all tyrosine residues participate in hormonogenesis
depends on their location; if they are too far apart, even with 3D modifications, are unable to react together and form dimers/oligomers
broad steps of TH synthesis (4)
- uptake of iodide
- incorporation - organification of iodide into tyrosine (iodination)
- coupling of iodinated tyrosines to form TH
- diffusion of TH into blood
rate limiting enzyme in thyroid gland
thyroperioxidase (TPO)
steps of iodination (2)
- inorganic iodide anion is oxidized to diatomic (molecular) iodine
- iodine covalently linked to tyrosyl residues
coupling of iodinated tyrosines to form TH
T3 -> DIT + MIT
T4 -> DIT + DIT
MIT and DIT: which is biologically active
DIT