Ursharona's List: endocriniology

• family of neurotransmitters that share a common molecular structure (namely, indolamine)
• common example of an indolamine is serotonin,a neurotransmitter involved in mood and sleep. Another example of an indolamine is melatonin, which regulates the sleep-wake cycle (circadian rhythm) in humans.
• In biochemistry, indoleamines are substituted indole compounds that contain an amino group. Examples of indoleamines include the lysergamides.

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• found at the apical (luminal) membrane of follicular cells in the thyroid gland.
• transports iodine from the cytoplasm to the follicle lumen.
• also found in the cells of the inner ear, where its function is not well understood.
• Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease
• syndrome is also characterized by hypothyroidism
• Another little-understood role of pendrin is in airway hyperreactivity and inflammation, as during asthma attacks and allergic reactions.

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• genetic disorder leading to congenital bilateral (both sides) sensorineural hearing loss and goitre with occasional hypothyroidism (decreased thyroid gland function)
• accounts for 7.5% of all cases of congenital deafness.^[3]

• NIS mediated uptake of iodide into follicular cells of the thyroid gland is the first step in the synthesis of thyroid hormone.^[4]
• Iodine uptake is a result of an active transport mechanism mediated by the NIS protein, which is found in the basolateral membrane of thyroid follicular cells
• As a result of this active transport, iodide concentration inside follicular cells of thyroid tissue is 20 to 50 times higher than in the plasma
• transport of iodide across the cell membrane is driven by the electrochemical gradient of sodium (the intracellular concentration of sodium is approximately 12 mM and extracellular concentration 140 mM)
• Once inside the follicular cells, the iodide diffuses to the apical membrane, where it is metabolically oxidized through the action of thyroid peroxidase to iodinium (I⁺) which in turn iodinates tyrosine residues of the thyroglobulin proteins in the follicle colloid.

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• Thyroglobulin (Tg) is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid.
• should not be confused with Thyroxine-binding globulin, a carrier protein responsible for carrying the thyroid hormones in the blood.
• The active form of triiodothyronine, 3, 5, 3' triiodothyronine, is produced both within the thyroid gland and in the periphery by 5'-deiodinase
• In fact, the Tg molecule, which contains approximately 120 tyrosyl residues, is able to form only very small amounts of thyroid hormone (5-6 molecules of T4 and T3).
• • NOTE: THRYOXINE=T4
    T3=triiodothyronine 
• Patients with Hashimoto's thyroiditis or Graves' disease frequently develop antibodies against Tg. Tg-specific antibodies help in the diagnosis of these diseases, but they also may be present in apparently healthy euthyroid individuals.
• Via a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues in thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT).
• • Thyroxine is produced by combining two moieties of DIT.
   
  • Triiodothyronine is produced by combining one molecule of MIT and one molecule of DIT.
• Small globules of the follicular colloid (Tg) are endocytosed (hormone (TSH)-mediated) and proteases in lysosomes digest iodinated thyroglobulin, releasing T3 and T4 within the thyrocyte cytoplasm
• T3 and T4 are then transported across (TSH-mediated) the basolateral thyrocyte membrane, into the bloodstream, by an unknown mechanism while the lysosome is recycled back to the follicular lumen.

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• The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is primarily present in steroid-producing cells, including theca cells and luteal cells in the ovary, Leydig cells in the testis and cell types in the adrenal cortex.
• Cholesterol needs to be transferred from the outer mitochondrial membrane to the inner membrane where cytochrome P450scc enzyme cleaves the cholesterol side chain, which is the first enzymatic step in all steroid synthesis

• ACTH is synthesized from pre-pro-opiomelanocortin (pre-POMC).
• ACTH and β-lipotropin are secreted from corticotropes in the anterior lobe (or adenohypophysis) of the pituitary gland in response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus.