Thyroid Gland Flashcards
Overview - function of thyroid
Developmental
Essential for normal development, especially CNS
and bone • Metabolic
Essential for normal metabolism of many body
tissues
Describe blood supply of thyroid gland
Rich blood supply: More blood
per unit weight than kidney ● Inferior thyroid artery from
subclavian ● Superior thyroid artery from
carotid
Describe histology of thyroid Gland
Red arrows: follicular cells Blue arrows: colloid (mainly thyroblobulin)
Yellow arrow: c-cell (parafollicular cell)
Follicular cells synthesize and secrete TH
C-cells secrete calcitonin (not considered here)
What are thyroid hormones derived from.
Two iodinated tyrosine molecules
T4: major form released to blood, less active
(prohormone) • T3: active form, converted in target cells
TH synthesis: steps
Active uptake of I- across basolateral membrane, against concentration
and electrical gradient, by Na/I symporter (NIS). Stimulated by TSH. 2. Iodide efflux (diffusion) across apical membrane via exchanger known
as pendrin (PDS). 3. At extracellular apical membrane iodide is oxidized to iodine and
covalently bound to tyrosine residues within the thyroglobulin (TG)
macromolecule. Requires thyroid peroxidase (TPO) and H2O2. 4. Tyrosine residues may be iodinated in one (mono-iodotyrosine, MIT) or
two (DIT) positions. Coupling of iodotyrosine residues (catalysed by
TPO) produces T4 (DIT-DIT) and a smaller amount of T3 (MIT-DIT).
TH release: steps
Under the influence of TSH, colloid droplets consisting of thyroid
hormones within the thyroglobulin molecules are taken back up into the
follicular cells by pinocytosis. 6. Fusion of colloid droplets with lysosomes causes hydrolysis of
thyroglobulin and release of T3 and T4. 7. About 10% of T4 undergoes mono- deiodination to T3 before it is
secreted. The released iodide is reutilized. Several-fold more iodide is
reused than is taken from the blood each day but in states of iodide
excess there is loss from the thyroid. 8. Approximately 100 μg TH secreted per day (90% T4 and about 10%
T3). Secretion probably relies on membrane transporter
How do thyroid hormone act on target tissue
TH receptors (TRs) belong to the nuclear receptor superfamily
• Ligand-activated transcription factors High affinity for T3
• Activation requires dimerization with another TR or
retinoid X receptor (RXR) • TRs encoded by two genes: TR alpha and TR beta
Why are there different isoforms of tyrosine
Isoforms due to splicing
What do selenodeiodinases do
Activate and deactivate t3 and 4
Funcyoos of TH
General - increase metabolic rate
Increase metabolic rate
• Number and size of mitochondria, enzymes in
metabolic chain, Na/K ATPase activity • Positive inotropic and chronotropic effects on heart • Synergizes with sympathetic nervous system
• Energy metabolism
• Partially antagonizes insulin signalling
• Gluconeogenesis, lipolysis • Growth and development
What if the function of The hypothalamic-pituitary-thyroid axis and how
Negative feedback control of thyroid hormone
synthesis and secretion, via the hypothalamo-
pituitary axis
Hypothalamic neurosecretory cells release
thyrotrophin-releasing hormone (TRH) into the
portal capillaries
What does trh stimulate
TRH stimulates thyrotrophs of anterior pituitary
to secrete thyroid stimulating hormone (TSH)
What is the lack of inhibition equivalent to
Excitation
What are the actions if tsh
Increases iodine uptake • Stimulates other reactions involved in TH
synthesis (e.g., TPO) • Stimulates uptake of colloid • Induces growth of thyroid gland
(which can lead to goitre)
What is Hypo- and hyperthyroidism
Euthyroid: normal thyroid function • Hyperthyroidism: TH excess
• Primary: problem is thyroid gland itself
• Secondary: problem is pituitary regulation • Hypothyroidism: TH deficiency
