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Biochemistry 2280A
Tom Stavraky

Endocrinology 1. Describe the functional anatomy of the hypothalamic-pituitary unit hypothalamus surrounds or lines the 3 ventricle of the brain immediately superior to the pituitary. Connected to the pituitary by a narrow stalk of unmyelinated axons and network of blood vessels. Neurohypophysis (posterior pituitary) and adenohypophysis (anterior pituitary). 2. Name the types of hypothalamic neurons and their functions Magnocellular neurons terminate in posterior pituitary and secrte vasopressin and oxytocin, parvicellular secrete release/inhibiting hypophyseal factors into portal system such as TRH, CRH, GHRH, GnRH, hypothalamic projection neuron synapses with neuronal targets. 3. Describe the terms circadian, diurnal, ultradian Episodic secretion in rhythms that are: circadian is around 24 hours, diurnal is exactly 24 hours and ultradian is minutes of hours 4. Discuss the generation and importance of episodic endocrine secretion. Secreted in bursts 5. Outline the 5 hypothalamic-anterior pituitary axes and 2 posterior pituitary axes - ACTH is derived from POMC (also makes α- MSH and B-endorphins) - α-subunit is common to FSH and LH, heavily glycosylated GH acts on TKAR (tyrosine kinase-associated receptor - generally anabolic - PRL release is controlled by TRH (positive) and dopamine and PIF (negative). - Receptors are TKAR - Usually under tonic inhibition by dopamine - Estradiol stimulates PRL secretion - Plays a major role in maintenance of teticular LH receptors - common α subunit - AVP and OXY are made with neurophysin (prevents axonal leackage) and GP/ Vasopressin – stimulated by osmoreceptors (oragnum vasculosum of the lateral terminalis), baroreceptors and volume receptors. Renin-agiotensin system is also involved. Oxytocin – released following mechanical stimulation to the nipple, stimulates contraction of ductual myoepithelium. Also causes contraction of smooth muscle in response to vaginal stimulation or cervical stretching. Possibly involved in feeding behaviour and satiety, gastric acid secretion, BP, temp and HR, stimulation of glucagons secretion, stress responses, tubule contraction and sperm transfer to testes. 6. Define the major endocrine disorders associated with the posterior pituitary Diabetes Insipidus – Hypothalamic or central DI is due to lack of vasopressin. Causes large urine volume that is hypotonic and dilute and often accompanied by polydipsia (excessive thirst). Can be caused by tumours, hereditary, granulomatous diseases, sarcoidosis. SIADH – Syndrome of Inappropriate Anti-Diuretic Hromone Secretion. Decreased plasma osmolality, inappropriate urine concentration (elevated Na+), euvolemic. May be caused by tumours, CSN disorders, drug-induced, pulmonary disease. Thyroid Gland 1. Locate and describe the anatomy of the thyroid - bilobed gland of endodermal origin, lies of the ventral surface of the trachea below the cricoid cartilage. About 15-20 grams in humans. 2. Describe the role of thyroglobulin - Thyroglobulin is high MY, heavily glycoslated, About 330 tyrosine residues which can be iodinated to form thyroxine (T4) and triiodothyronin (T3). 3. Explain the mechanism and regulation of thyroid hormone formation and the role of pituitary TSH - Thyroid cells have sodium iodide symporter (NIS) (requires Na/K ATPase). Pendrin is the apical iodide transporter. - Thyroperoxidases oxidize the iodine and iodinate tyrosine residues on TG (1-2 added) - TSH mostly stimulates iodide transport and TPO activity and Tg production 4. Discuss the factors regulating thyroid hormone levels (binding proteins, deiodinases, clearance) - Since steroids, must bind transport protein. Thyroxine binding globulin (TBG) transports 75% T3 and T4, high binding affinity. Transthyretin (TTR) transports 20% of T4 and 5% T3. Human Serum Albumin transports 5% T4 and 20% T3. Low binding, but lots available. o Binding proteins regulate the bioavailability and half-life of T3/T4. Without, would be rapidly cleared. - T4 is converted to T3 by deiodinases 5. Explain the cellular mechanism of action of thyroid hormone - Thyroid hormone receptors acts a transcriptional repressor (is a nuclear receptor) in a complex with retinoid X receptor (RXR). At low levels, T3 releases co-repression, at high levels, recruits co-activators. 6. Define the physiological role of thyroid hormones in development and the adult including major effects on cellular metabolism. - Required for the secretion and action of GH, essential for early neural development, maternal T3/T4 can compensate. Lack of maternal T3/T4 can result in growth retardation and cretinism - In adults increases basal metabolic rate, mitochondrial growth, replication and activity. Stimulates Na/K ATPase, increases transcription of metabolism enzymes, permissive to action of GH, induces expression of GH, PRL, NGF, surfactant, generally increase cellular metabolic activity. 7. Illustrate examples of thyroid pathology Edemic Goiter – lack of (-) feedback, no iodine available. Hashimoto’s – autoimmune disorder where antibodies to the TPO enzyme are formed, inhibits T3 and T4 production. - Both are hypothyroidism and can result in slower HR, muscle cramping, feeling cold, puffy eyelids, lack of concentration and poor memory, and lack of energy. - Hyperthyroidism – feeling hot, increased sweating, fast HR, nervousness, trembling Grave’s Disease – antibodies to TSH receptor 8. Name my least favourite hormone Calcitonin – inhibits osteoclas activity, decreases Ca++ tubular reabsorption. Lowers Ca++ levels. Insulin and Glucose Homeostasis 1. Compare and contrat metabolsi mduring the absorptive and post-absorptive states Absorptive State: Net uptake of glucose, glycogenesis, net protein synthesis Post-absorptive State: hepatic glycogenolysis, gluconeogenesis, lipolysis. 2. Define chylomicrons and VLDL - chylomicrons are large lipoprotein particles that transport dietary proteins. They are manufactured in epithelial cells in small intestine. Triglycerides, cholesterol, cholesterol, esters, and apoproteins, transported via the lymphatic system. - VLDL is a very low density lipoprotein, made by the liver. Broken down to free fatty acids and glycerol by lipoprotein lipase in endothelial cells, re-assembled in adipose cells. 3. Disucss the importance of the various subtypes of glucose transporters GLUT1 – in the brain, erythrocytes, placenta, fetal tissue. Low Km, constant uptake of glucose GLUT2 – liver, kidney, intestine, pancreatic B-cells. High Km, glucose equilibrium across membrane GLUT3 – brain. Medium Km, insulin-sensitive GLUT4 – muscle and adipose. Med Km and also insulin-sensitive GLUT5 – jejunum. Medium Km, fructose uptake. 4. Name the endocrine cells of the pancreas and their hormones - Alpha-cells produce glucagons, beta-cells produce insulin and amyloid, delta-cells produce somatostatin, D1 cells produce VIP, PP cells produce pancreatic polypeptide 5. Describe the mechanism of glucose regulation of insulin secretion - First peak 1-5 min of glucose load, 2 peak occurs 15-20 min later. 6. Describe the cellular mechanism of action of insulin st - Second longer phase of insulin secretion is largely dependent on the 1 phase. The rise in intracellular Ca++ activates CaM kinase which activates transcription of the insulin gene. Secreted insulin binds to B cell insulin receptors which increases transcription of the insulin gene via the PI3kinase pathway. Insulin receptor: has IgG domain, cystine-rich region, transmembrane domain, kinase domain, protein interaction domain and c-term tail. Second messangers include STATs, PI3K, PLC, MAPK. Uses IRS proteins. Signal Termination: receptor dephosphorylation, Ca++ pumps, ph
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