Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Ca and Thyroid Regulation CALCIUM REGULATING HORMONES 13 • Introduction: effects of Ca / PO4 ions; Parathyroid: anatomy, histology, PTH; Thyroid: anatomy, histology, Calcitonin; Kidney: Vit D. Overview of Ca regulation: bone, kidney, and GI tract as effectors of Ca regulating hormones. • PTH: structure, receptor, secretion, effect of Ca / Vit D metabolites / other factors, effects • Calcitonin: structure, biological actions, effect on osteoclasts and bone reabsorption • Vit D: production and metabolism, absorption, transport and excretion, biological actions • Diseases: hypoPTH, low Ca tetany, hyperPTH, kidney stones, rickets, osteoporosis. Case study (e.g. hypocalciuric hypercalcemia) Ca and Thyroid Regulation THYROID AND ITS REGULATION • Introduction to the thyroid: anatomy, histology, hierarchy, feed-back regulation, effect of T3-T4 on Na/K ATPase and uncoupling proteins • Biosynthesis of T3-T4: thyroglobulin, iodide pump, iodination and coupling reactions, lysosomes • T3-T4 effects: metabolism, T°C/F control, growth / development, reproduction, tertiary hypometabolism (starvation, hibernation) • mechanism of action: T4 to T3, T3 receptor, nuclear / mitochondrial sites, increase enzymes, Na/ K ATPase, uncoupling proteins • Pathology: goitrogens, hypo and hyperthyroidism, thyroid hormone resistance Page 1 13 Ca and Thyroid Regulation Ca Regulating Hormones PTH and Vit.D increase blood Ca while Calcitonin decreases it Vit. D absorption intestine blood Ca PTH resorption bone formation Calcitonin reabsorption PTH secretion Calcitonin filtration kidney blood Ca decrease bone formation, osteoblast kidney, Ca filtration intestine, Ca secretion calcium receptor parathyroid gland PTH PTH receptor Gs / AC Gq / PLC bone resorption, osteoclast kidney, Ca reabsorption, Vit. D intestine, Ca absorption Calcitonin receptor Gs / AC Calcitonin thyroid gland calcium receptor blood Ca increas e The Ca sensor is a GPCR and the Ca regulating hormones are PTH, calcitonin and Vit D Page 2 Ca Regulating Hormones PTH PTH is only made in the parathyroid gland. PTH activates both AC and PLC Ca Regulating Hormones Calcitonin The mechanism of action elicited by calcitonin involves AC and cAMP Page 3 Ca Regulating Hormones Vit D Vit.D activation is inhibited in the kidney by PO4 and in the parathyroid by Ca on PTH Ca Regulating Hormones A model for the general control of bone turnover Page 4 Thyroid and its Regulation TRH TSH TSH secretion is controlled mainly by a negative feedback of T3 - T4 Thyroid and its Regulation Thyroid hormones (T3 - T4) derived from the amino-acid tyrosine Page 5 Thyroid and its Regulation Hypothalamic Hypometabolic Condition (as seen in starvation and hibernation) T3-T4 (low) TSH (low / normal) TRH mRNA (low) UC proteins (low) TRH-induced TSH release (high) TRH release (low) SS inhibits TSH release Insulin (low) Glucagon (high) Cortisol (high) Epinephrine (high) LH/FSH (low) Leptin (low) Cas, NPY, aMSH, arcuate thermogenesis (low) energy expenditure (low) This condition is also known as Tertiary Hypometabolism T3 - T4 have multiple physiological effects Thyroid and its Regulation Mechanism of Action TSH hormone signal can be increased by rising cAMP or by decreasing phosphodiesterase TRH is associated with a GCPR linked to PLC; TSH is associated with GPCR linked to AC; Vit D is associated intracellular receptors (genomic) Page 6 Thyroid and its Regulation Characteristic manifestations of hyper and hypothyroidism Ca and Thyroid Regulation Page 7 Ca and Thyroid Regulation structure function Which, increase or decrease? a) b) How do you know? c) Parts to total? d) Two feedbacks and an absolute requirement? Ca and Thyroid Regulation HPT axis PTH Hyp Ca regulation Bone Ca TRH PTH Kidney Pit Ca Parathyroid Calcemia TSH VitD Thy VitD Gut Ca Thyroid Ca T3-T4 Calcitonin Ca S E Page 8 Next week question (after the test #1) Page 9