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USC BISC 307L - Thyroid and Growth Hormone 1
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Glucocorticoids last slideStress activated many areas of the brainHave sympathetic and parasympathetic responsesEpinephrine is rapidly acting and cortisol is slower and more persistentBut they share similar functionsEpinephrine inhibits many of the functions that parasympathetic system would enhanceNeurons activated will use norepi as a transmitter as well as CRH as a transmitterNorepi neurons mediate appropriate aggressive responsesCRH neurons inhibit appetite and growth and reproduction*Cross talk between the right hand (endocrine side) and left side (neural side)Cortisol also has effects on feedingThyroid Hormone, Growth HormoneThyroid FolliclesGrowth of skeleton requires Ca2+Thyroid gland is in neck and wraps around in front of larynx. Within the thyroid gland the functional unit is the thyroid follicle:Spherical organs (sphere of a layer of epithelial cells) filled with colloidIn between the follicles there are C cells and these C cells secrete calcitoninYellow stuff is the colloid thus the apical side is downwardCells secrete protein into the colloid and the protein being secreted is1. Thyroglobulin – most abundantrich in tyrosine residuessynthesis happens extracellular in the colloid2. Iodide ionsBrought in by sodium iodide symporterOnly place in the body where there is known to be a dietary requirement for iodideTaken against concentration gradientTransported by pendrin (Cl- and I- ions exchanger)Concentrated in the colloid materialNow we have all the materials to synthesize the thyroid hormones so now what happens is the enzyme thyroid peroxidase takes the iodide ion and adds it to the tyrosine residue of the thyroglobulin.This forms MIT (monoiodotyrosine)Can also add another atom of iodide to make DIT (diiodotyrosine)Then other enzymes take a DIT and another MIT or DIT and covalently link them together to make T3 (triiodothryornine) and T4 (tetraiodothyronine)THESE ARE THE THYROID HORMONESCant go anywhere yet because still cross-linked and insolubleImportant because T3 and T4 are highly lipid soluble and if they were not covalently bound they would diffuse awayUnusual way to store a lipophilic hormoneOnly 2 lipophilic hormones that are made in advance and storedHormone released under the stimulation of an anterior pituitary hormone, it will make the cell exocytose the hormones and when liberated T3 and T4 take offMade, stored, and releasedThyroid hormonesTBG binds T4 a lot more than T3Structures of the 2 thyroid hormones – don’t need to memorize structure of these. Look sort of like two tyrosines linked together and if you take one off T4 can become T3Most circulating thyroid hormone is T4 in humans (preferred)When T4 diffuses into target cells and target cells have varying levels of an deiodinase enzymes which will convert it to T3.T3 is more potent in bringing about the effects on the right so it is better for the hormone to effect cells in T3 form.Why would there be more T4 circulating then?Makes it possible for each target cell to adjust its sensitivity to thyroid hormone (how much the cell really needs to be stimulated)Effects are summarized by stimulation of metabolismHormones bind to nuclear receptors and they become a transcription factor in the nucleus which turns on other transcription factors and results in up regulation of many different proteinsStimulates Na+/K+ ATPaseSynthesizes more pumpsOxidative phosphorylation up regulatedTo support this metabolism there’s an increase in respiratory rate as well as heart rate and appetiteGrowth promoting hormoneCartilage and boneMuscleTissues that need thyroid hormoneBrainThey don’t cross the placenta much so maternal thyroid gland doesn’t help much so baby’s thyroid gland becomes active really early in growth and developmentControl of Thyroid Secretion/ PathologiesWhat goes wrong?Undersecretion or oversecretion of hormoneThyroid follicle cells are stimulated by TSH (anterior pituitary tropic hormone)TSH stimulated by hypothalamic hormone TRH (Thryotropin releasing hormone)T4 and T3 inhibit the secretion of these two hormones (TSH and TRH)1. Primary hypothyroidismcauses I insufficiency goiter (massive enlargement of the thyroid gland)due to I dietary insufficiencyNo feedback inhibition of TRH and TSH if no thyroid hormone being synthesized which stimulates everything to growHypothyroid symptoms – low hormone levelsMetabolism levels lowLethargic and mentally slowIntolerance to coldYoung women are hypothyroid sometimesTreatment: Iodine2. Hashimoto’s diseasemost common form of hypothyroidism in the USautoimmune disease in which T cells attack and destroy thyroid follicle cells resulting in less secretion of T4 and T3 resulting in hypothyroid symptomsTreatment: Need to take synthetic thyroid hormones3. Graves diseaseautoimmune diseaseB cell attack Abs being made against the TSH receptors stimulating the receptor causing more T4 and T3 to be secreted so high levels will result in low levels of TRH and TSHHyperthyroid conditionIncrease in metabolismIntolerance to heatIncreased anxiety and respiratory functionConnective tissue on the back of the orbits pushes the eyes forwardHave goiter also- not only in hypothyroid conditionTreatment: remove part thyroid gland but make sure not to remove the parathyroid gland (required for life) or you could inhibit the synthesis of thyroid hormones with drugs. Can inhibit with potent iodineNot really treatableEffects of Growth Hormones (somatotropin)Secreted by anterior pituitaryIndirectMitogenic effects on many tissues, via IGF-I productionMake insulin like growth factor 1Secondary hormone that is secreted to mediate the effects of growth hormoneMain effects of growth hormone are indirectDirectStimulates: many anabolic reactions protein and RNA synthesis lipolysisOverallIncrease in lean body mass and decrease in fat contentIncreased organ size especially bones heart and lungsEffects on long bones important in determining heightBISC 307L 1st Edition Lecture 17 Current Lecture Glucocorticoids last slide-- Stress activated many areas of the braino Have sympathetic and parasympathetic responseso Epinephrine is rapidly acting and cortisol is slower and more persistento But they share similar functions o Epinephrine inhibits many of the functions that parasympathetic system would enhanceo Neurons activated will use norepi as a transmitter as well as CRH as a transmittero Norepi neurons mediate appropriate aggressive responseso CRH neurons inhibit appetite and growth


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