IPHY 4440 1st Edition Lecture 16Outline of Last Lecture I. Thyroid Gland Outline of Current Lecture II. Thyronine metabolism III. Thyroid Hormone actionsIV. Metabolic Actions V. Growth and differentiationVI. Clinical aspects of thyroid physiologyCurrent LectureI. Thyronine metabolism A. Deiodinase typesi. Scheme 1a) Outer ring deidodinase= 5’-deiodinase (5’-D). T4 T3b) Inner ring deiodinase= 5-deiodinase (5-D). T3T4 & T3 T2ii. Scheme 2Type I: in liver, kidney, and thyroid. Activation & inactivation. Both 5 and 5’  T3, rT3 and T2Type II: in brain, pituitary, placenta. Activation. 5 only  T3Type III: in brain, skin, placenta, gut. Inactivation. 5 only  rT3, T2iii. Thyroid BioassaysA. Thyroid cell height- Height of follicular epithelium (Proportional to thyroid state and TSH level) - Squamous: Low “activity”  hypothyroid (Low TH)- Cuboidal: Normal “activity”  low cuboidal (Euthyroid= normal TH)- Columnar: high “activity” - Tall cuboidal and columnar hyperthyroid - Biopsy: measure epithelial cell height, what does that tell yuou about TSH level?- What does this tell you about T4 or T3? Not much Radioiodide uptake: radioactive isotopes These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Cold nodules: inactive sites (TcO4 & 123I)- Hot nodules: some are not detected with 123I- Uptake reflects TSH levelII. Thyroid Hormone actionsHow do T3 and T4 get to target cells?- TBGs (a2globulins, prealbumin, and albumin) How do T3 and T4 enter target cells? Organic anion transporter polypeptides (oatps)- MCT8: MonoCarboxylate Transporter gene 8 How do they produce their effects in target cells? - Nuclear receptors in nucleus: TR-RXR binds to TRE- Plasma membrane receptors (rare): MAPK activationIII. Metabolic Actions 1) Controls BMR= basal metabolic rate, measured as O2 consumption- TH increases, BMR increases 2) Thermogenic action (Chronic) [Epinephrine for acute response]a. BMR ® heat production= Acclimation to chronic cold e.g.,arousal from hibernationb. Uncoupling of oxidative phosphorylation: T3 synthesis of Uncoupling protein 1 (UCP-1)c. Synthesis of other mitochondrial proteins: (+) Succinoxidase (+) Cytochrome C (+) Cytochrome oxidaseIV. Growth and differentiation1) Synergistic with GH on body (combined effect >> added effect)2) Nervous system development: could be the most important action of THs in the fetus 3) Nervous system function: Also essential for normal functioning in children and adults. Hypothyroid people exhibit slow mental activity4) Hair replacement: low TH + high F  hair loss and high TH + low F  hair growth5) Reproduction1. Hypothyroid Individualsa. Delayed sexual maturationb. Decreased androgen (males)c. Irregular ovarian cycles (females) 6) Permissive roles1. Enhances other regulatorsa. Increases adenylyl cyclase levelsb. Affects responsiveness of CNSc. Hypothyroidism depresses all body functions VIII. Clinical aspects of thyroid physiology- Symptoms of hyper& hypothyroidism- Hypo: mental retardation, physically sluggish, sensitive to cold, hypophagic, low BMR- Hyper: mentally uick, restless, irritable, wakeful, sensitive to heat, hyperphagic, high BMRA. Hyperthyroidism- thyrotoxicosis1) Primary: the problem lies within the thyroid gland a. Toxic multinodular goiters- Multiple aggregates of hyperactive follicles- Several large hyperactive follicles* May or may not be TSH-dependent2) Secondary: The problem NOT within thryoid glanda. Graves’ Disease (autoimmune disease)Female 20X > male- LATS (abnormal TSH antibodies) Long Acting Thyroid Stimulator- Binds to TSH receptora. Choriocarcinomas: plancenta  TSHb. Pituitary adenomas  TSH Very rareUnresponsive to (-) feedback by THB. Hypothyroidism* low thyroid hormones: Dietary iodide deficiency commonThyroid hormone resistance: tissues not responding to TH1. Myxedema: no thyroid hormones in adultJuvenile myxedema: cretinism, 1 in 8500 births  severe mental retardation ~ *Prevented by thyroid