BISC 307L 1st Edition Lecture 17 Current Lecture Glucocorticoids last slide Stress activated many areas of the brain o Have sympathetic and parasympathetic responses o Epinephrine is rapidly acting and cortisol is slower and more persistent o But they share similar functions o Epinephrine inhibits many of the functions that parasympathetic system would enhance o Neurons activated will use norepi as a transmitter as well as CRH as a transmitter o Norepi neurons mediate appropriate aggressive responses o CRH neurons inhibit appetite and growth and reproduction o Cross talk between the right hand endocrine side and left side neural side o Cortisol also has effects on feeding Thyroid Hormone Growth Hormone Thyroid Follicles o o Growth of skeleton requires Ca2 o 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 colloid In between the follicles there are C cells and these C cells secrete calcitonin Yellow stuff is the colloid thus the apical side is downward Cells secrete protein into the colloid and the protein being secreted is 1 Thyroglobulin most abundant rich in tyrosine residues synthesis happens extracellular in the colloid 2 Iodide ions Brought in by sodium iodide symporter Only place in the body where there is known to be a dietary requirement for iodide Taken against concentration gradient Transported by pendrin Cl and I ions exchanger Concentrated in the colloid material Now 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 HORMONES Cant go anywhere yet because still cross linked and insoluble Important because T3 and T4 are highly lipid soluble and if they were not covalently bound they would diffuse away Unusual way to store a lipophilic hormone Only 2 lipophilic hormones that are made in advance and stored Hormone released under the stimulation of an anterior pituitary hormone it will make the cell exocytose the hormones and when liberated T3 and T4 take off Made stored and released Thyroid hormones o o TBG binds T4 a lot more than T3 o Structures 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 T3 Most 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 metabolism Hormones 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 proteins Stimulates Na K ATPase Synthesizes more pumps Oxidative phosphorylation up regulated To support this metabolism there s an increase in respiratory rate as well as heart rate and appetite Growth promoting hormone Cartilage and bone Muscle Tissues that need thyroid hormone Brain They 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 development Control of Thyroid Secretion Pathologies o o What goes wrong Undersecretion or oversecretion of hormone Thyroid 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 hypothyroidism causes I insufficiency goiter massive enlargement of the thyroid gland due to I dietary insufficiency No feedback inhibition of TRH and TSH if no thyroid hormone being synthesized which stimulates everything to grow Hypothyroid symptoms low hormone levels Metabolism levels low Lethargic and mentally slow Intolerance to cold Young women are hypothyroid sometimes Treatment Iodine 2 Hashimoto s disease most common form of hypothyroidism in the US autoimmune disease in which T cells attack and destroy thyroid follicle cells resulting in less secretion of T4 and T3 resulting in hypothyroid symptoms Treatment Need to take synthetic thyroid hormones 3 Graves disease autoimmune disease B 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 TSH Hyperthyroid condition Increase in metabolism Intolerance to heat Increased anxiety and respiratory function Connective tissue on the back of the orbits pushes the eyes forward Have goiter also not only in hypothyroid condition Treatment 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 iodine Not really treatable Effects of Growth Hormones somatotropin o Secreted by anterior pituitary o Indirect Mitogenic effects on many tissues via IGF I production Make insulin like growth factor 1 Secondary hormone that is secreted to mediate the effects of growth hormone Main effects of growth hormone are indirect o Direct Stimulates many anabolic reactions protein and RNA synthesis lipolysis o Overall Increase in lean body mass and decrease in fat content Increased organ size especially bones heart and lungs Effects on long bones important in determining height