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PCB 4723C

Topic 15 Tuesday, November 12, 2013 1:53 PM • Endocrine system controls things that don’t need to happen instantaneously (metabolicrate, kidney function, growth, development,reproductivecycles) • Once hormonesare secreted, they can circulate either free or bound to carrier proteins • Endocrine regulation occurs through feedback control ○ Hormonesecreting cells function as sensors that continually monitorthe circulating concentrationof some regulated variable ○ When the endocrine gland senses that too much or too little of the regulated variable is circulating in blood, it responds by decreasing or increasing the rate of hormone secretion ○ This response, in turn, affects the metabolicor secretorybehavior of the target tissue, which may either directly feed back to the sensing cell or stimulate someother cell that eventually signals the sensor regarding whether the altered function of the endocrine gland has been effective ○ ○ For example, beta cells in pancreatic islets detect plasma glucose concentration ○ If glucose is too high, it responds by increasing secretion of insulin ○ Insulin acts on liver or muscle (target 1) to modulate its production of glucose (other hormoneor metabolite)  This may affect a second tissue, such as making glucose available in the brain ○ The glucose (other hormone or metabolite)concentration feeds back to the sensor, telling the sensor when the glucose level is back to normal (and to stop producing insulin) • Protein/peptide hormones ○ Can evolve ○ Translated and processed ○ Most peptide hormonesexist free in the circulation ○ Bind to cell surface receptors and activate a variety of signal transduction systems  G proteins coupled to adenylyl cyclase  G proteins coupled to phospholipase C  G proteins coupled to phospholipase A2  Guanylyl cyclase  Receptor tyrosinekinases  Tyrosine Kinase-AssociatedReceptors ○ Synthesized on the rough end of the ER of different endocrine cells  Usually synthesized first as larger proteins that are not biologically active (preprohormone)and are cleaved to form smaller prohormonesin the ENR (preprohormone)and are cleaved to form smaller prohormonesin the ENR  Transferred to the Golgi for packaging into secretoryvesicles  Enzymes in the vesicles cleave the prohormonesinto smaller, biologically active hormones(as well as the inactive fragments)  Vesicles are stored within the cytoplasmand many are bound to the cell membrane until their secretion is needed Usually released in response to increased cytosoliccalcium concentrationcaused by  depolarization or increased cAMP and subsequent activation of protein kinases that initiate secretion of the hormone  ○ Response is usually rapid because second messenger systemsmodify existing proteins ○ All hormonesfrom the hypothalamus,anterior pituitary, posterior pituitary, pineal gland, pancreas, parathyroid gland, gastrointestinal tract, kidneys, liver, thyroid cells, heart • Amine hormones ○ Circulate bound to plasma proteins ○ Consists of Catecholamineand thyroid hormones,made from tyrosine  The adrenal medulla makes the catecholaminehormonesepinephrine, norepinephrine and ○ The adrenal medulla makes the catecholaminehormonesepinephrine, norepinephrine and dopamine from tyrosine   Epinephrine, the principle product of the adrenal medulla, is made ONLY in the adrenal medulla   Synthesized in the cytosolof chromaffin cells and stored in chromaffin granules found in the nucleus  Circulate in the blood half bound to plasma proteins  Activates second messenger systems  Norepinephrine is made in the adrenal medulla as well, but in a much smaller quantity ○ The thyroid hormonesthyroxine and triiodothyronineare synthesized from two tyrosines and iodine atoms  Behave more like steroid hormones,with intracellular receptors that activate genes, regulating metabolicrate  Mostly circulate bound to plasma proteins  Activates specific genes to produce new proteins that produce desired effects  Made ONLY from thyroid follicular cells, in colloid, which is an inland extra-cellular site □  Stored in colloid  Released by endocytosisof colloid • Steroid hormones ○ Circulate bound to plasma proteins ○ Must be made as needed because it is hard to contain (simply diffuses out as soon as it is made) • Synthesis and release is highly regulated (especially in comparison to degradation and excretion[clearance]) ○ Degradation and excretion is usually stable/constant ○ Hormonesare cleared form the plasma in several ways  Metabolic destruction by the tissue  Binding with the tissue  Excretion by the liver into the bile  Excretion by the kidneys into the urine • Hypothalamus controls pituitary secretion ○ Specialized neurons located within specific nuclei in the hypothalamus synthesize certai
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