The thyroid gland Flashcards
(15 cards)
give an overview of thyroid function
-developmental- essential for normal development; especially in CNS and bone during early life.
-lack of thyroid in early life causes irreversible neurological damage
-metabolic; essential for normal metabolism of many body tissues also in cardiovascular function
explain the anatomy and histology of the thyroid gland
Anatomy of the thyroid gland:
-usually has a left and right lobe but can sometimes have a third pyramidal lobe.
-rich blood supply from the inferior thyroid artery from the subclavian artery and superior thyroid artery as a branch of the external corotid artery.
Histology:
-a single layer of follicular cells surround the colloid (protein rich storage materal containing many hormones). These cells synthesise and release hormones into the colloid.
-the basal end of follicular cells face the capillaries whilst the apical faces the colloid.
-C-cells (aka parafollicular cells) secrete calcitonin which is involved in Ca2+ regulation.
explain thyroid hormones
-thyroid hormones can be tri- or tetra iodinated to form tyrosine (T4) or triiodothyronine (T3)
-T4 is less active than T3 but T3 also exists in an inactive form (reverse T3)
-The major form released into the bloodstream in T4 so it can be converted into T3 in target cells.
Explain TH synthesis
1) Iodide uptake against its concentration gradient by the Na+/I- symporter (NIS) from the blood-powered by the Na+ concentration gradient created by the Na+/K+ ATPase.
2) Iodide diffuses through the cell and then across the apical membrane into the colloid through a pendrin exchanger.
3) Iodide is oxidised into iodine by thyroid peroxidase (requires hydrogen peroxide and thyroglobulin which contains tyrosine residues).
4) This can be further converted into T3 or T4
explain TH release
1) The thyroid hormone in a colloid droplet with thyroglobulin is endocytosed into the follicular cell.
2) Here it combines with lysosomal enzymes which hydrolyse the thyroglobulin and release the T3/T4 units by cleavage.
3) Some T4 is converted into the active T3 before secetion into the circulation by transporters.
4) The iodine is recycled by deionizing enzyme DEHA-1.
5) Approximately 100ug TH secreted per day. Secretion probably relies on membrane transporter.
explain circulating thyroid hormones
-lipophillic so mostly 90% bound to plasma proteins
-mostly 70% bound to thyroid-binding globulin but some bound to transthyretin (10-20%) and some bound to albumin (10-20%)
-T4 is more common in the circulation but T3 is more important as its more active
explain thyroid hormone action on target tissues and thyroid hormone receptors
Thyroid hormone action on target tissues:
-TH receptors belong to the nuclear receptor superfamily;
* ligand-activated transcription factors
-high affinity for T3;
* activation requires dimerization with another TR or retinoid X receptor
* TRs encoded by two genes (TR alpha and TR beta which can each exist in 2 forms)
Thyroid hormone receptors:
-common feature of nuclear receptors include DNA binding domains, hormone binding domain and transactivation regulatory domain (bind to complexes of regulatory proteins)
-receptor dimerise (with eachother or with a retinoid x receptor) to become activated, they go through a conformational change which then alters regulatory proteins. This allows it to bind to DNA to modify transcription
explain metabolic regulation of thyroid hormones
-the relative levels of T3, T4 and inactive forms are controlled in target tissues by a family of 3 iodothyronine selenodeiodinases which are expressed in a tissue specific way.
-this is why the trace element selenium is essential in diet.
-these regulate the amount of T3 that is actually available to bind to receptors.
-D2 increases T3 levels by increasing conversion from T4 whilst D3 decreases T3.
discuss recently discovered TH transporters
-TH previously thought free to diffuse across cell membrane but it actually needs transporters.
-MCT8 mutations in gene discovered to underlie an X-linked condition:
* Allan-herndon-Dudley syndrome which is associated with psychomotor retardation and hyperthyroidism like symptoms.
explain functions of TH
Functions of TH:
-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 (promotes energy release rather than storage)
-Growth and development
explain hypothalamic- pituitary- thyroid axis
-negative feedback control of thyroid hormone synthesis and secretion, via the hypothalamic pituitary axis
-hypothalamic neurosecretory cells release thyrotrophin releasing hormone into the median eminence from which they are carries to the anterior pituitary via the portal vein.
-TRH stimulates thyrotrophs of anterior pituitary to secrete thyroid stimulating hormone (TSH). This then acts on the thyroid gland to produce thyroid hormone
explain negative feedback control of TH synthesis and secretion
-Congenital hypothyroidism;
* once the most common cause of intellectual disability-prevented by testing TSH levels using neonatal heal prick.
* primary; problems of the thyroid gland (e.g. no thyroid production from the gland means there is no feedback inhibition of TSH so TSH levels remain high)
* secondary; problems of the brain means although TRH is being produced, the pituitary isn’t signalling the thyroid gland to produce the hormone. This means TRH levels are high and both TSH and thyroid hormone levels are low
explain TSH receptor and its actions and hypo and hyperthyroidism
TSH receptor and its actions:
-7 transmembrane, G protein coupled receptors that mainly involve the cAMP pathway but can sometimes affect the PLC pathway.
actions;
* increased iodine and colloid uptake for TH sythesis
* induces gland growth which can lead to goitre as excess hormone is produced.
Hypo- and hyperthyroidism:
-euthyroid; normal thyroid function
-hyperthyroidism; TH excess
-primary; problem with thyroid gland itself so low TRH and TSH levels
-secondary; problem is pituitary regulation so low TRH but high TSH
-Hypothyroidism; TH deficiency so high TRH and TSH levels
explain grave’s disease; primary hyperthyroidism
-autoimune as auto-antibodies act on agonists and bind to the TSH receptors to activate them to release more thyroid hormone. This will reduce TSH by negative feedback but thyroid hormone will keep being produced as antibodies are still stimulating the receptor.
-high circulating thyroid hormone and low TSH
-weight loss, tachycardia, fatigue
-diffuse goitre (TSH receptor stimulation)
-Grave’s opthalmopathy- inflammation of muscles, eyes buldge out
explain Hashimoto’s; primary hypothyroidism
-autoimmune disease
-low thyroid hormone causes increased/high TSH due to negative feedback. Legarthy, intolerance to cold, delayed growth and development and goitre.
