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SC BIOL 460 - Priming Effect and Regulation

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Priming effectCan alter number of receptors in plasma membraneUpregulationHypothalamus produces gonadotropin RHInitially has small effectInitial exposure causes upregulationAdenohypophysis makes more receptorsSubsequent releases have more effect – similar to LTPDownregulationTarget cells exposed to high concentrations of polypeptide hormones for along timeTarget cells begin removing receptorsHormone has less effectTo avoid down regulation – many polypeptide hormones are released in spurts – pulsatile secretionGonadotropin Releasing Hormone AgonistDrug that causes downregulationHelps with two conditionsBenign prostatic hyperplasiaEnlarged prostateLess FSH/LHNo testosteroneNo growth of prostate glandEndometriosisSome cells of stratum functionalis detach and work their way into body cavityFSH/LH cause increase in cell division through estrogenThis can cause scarring and infertilityParacrine RegulationSignaling molecules released by cells in an organ that affect cells in the same organGrowth factorsCytokines – produced by immune systemLymphokines – cytokines made by lymphocyteProstaglandinsGroup of paracrine factors/regulators (70-75 types)Discovered by Ulf von Euler in human semenThought they were produced by prostate glandActually produced in all cellsTakes phospholipid from PM, breaks down via phospholipase A2, producing arachidonic acidArachidonic acid is an eicosanoid – 20 carbons2 enzymescyclooxygenase – makes prostaglandins (ecosanoid w/ five membered ring)Lipoxygenase – leukotriene (another PF), causes asthmaZyflo – inhibits lipoxygenaseSingulair – blocks glucotriene receptorsProstaglandin EffectsOften antagonistc1 involved in blood clotting, another prevents clottingsome cause uterine contractions, ovulationinvolved in immune system – fever development, painin gastrointestinal tract – block acid secretion, produce protective mucusblood supply to kidneys – causes adequate supplyNSAIDS (non-steroidal anti-inflammatory drugs)AspirinIbuprofen, motrinAleveInhibit all isoenzymes equallyInhibit cyclooxygenaseLong term use causes harsh side effects, such as gastric ulcersCan eventually cause kidney failure3 Isoenzymes of cyclooxygenaseCOX-1: important prostaglandins – blood to kidney, suppressing acid in stomach, secretion of stomach mucus, produced constitutivelyCOX-2: only produced in response to inflammationCaused by cytokinesCOX-2 causes inflammation, feverMade antagonists for COX-2 (no inflammation, other processes still functioning)CelebrexVioxx (off market now)Block COX-2 onlyCOX-3Only in CNSNo effect on inflammationEnhances perception of pianCauses fever and headachesAcetaminophen – Tylenol; inhibits COX-3Priming effectCan alter number of receptors in plasma membraneUpregulationHypothalamus produces gonadotropin RHInitially has small effectInitial exposure causes upregulationAdenohypophysis makes more receptorsSubsequent releases have more effect – similar to LTPDownregulationTarget cells exposed to high concentrations of polypeptide hormones for along timeTarget cells begin removing receptorsHormone has less effectTo avoid down regulation – many polypeptide hormones are released in spurts – pulsatile secretionGonadotropin Releasing Hormone AgonistDrug that causes downregulationHelps with two conditionsBenign prostatic hyperplasiaEnlarged prostateLess FSH/LHNo testosteroneNo growth of prostate glandEndometriosisSome cells of stratum functionalis detach and work their way into body cavityFSH/LH cause increase in cell division through estrogenThis can cause scarring and infertilityParacrine RegulationSignaling molecules released by cells in an organ that affect cells in the same organGrowth factorsCytokines – produced by immune systemLymphokines – cytokines made by lymphocyteProstaglandinsGroup of paracrine factors/regulators (70-75 types)Discovered by Ulf von Euler in human semenThought they were produced by prostate glandActually produced in all cellsTakes phospholipid from PM, breaks down via phospholipase A2, producing arachidonic acidArachidonic acid is an eicosanoid – 20 carbons2 enzymescyclooxygenase – makes prostaglandins (ecosanoid w/ five membered ring)Lipoxygenase – leukotriene (another PF), causes asthmaZyflo – inhibits lipoxygenaseSingulair – blocks glucotriene receptorsProstaglandin EffectsOften antagonistc1 involved in blood clotting, another prevents clottingsome cause uterine contractions, ovulationinvolved in immune system – fever development, painin gastrointestinal tract – block acid secretion, produce protective mucusblood supply to kidneys – causes adequate supplyNSAIDS (non-steroidal anti-inflammatory drugs)AspirinIbuprofen, motrinAleveInhibit all isoenzymes equallyInhibit cyclooxygenaseLong term use causes harsh side effects, such as gastric ulcersCan eventually cause kidney failure3 Isoenzymes of cyclooxygenaseCOX-1: important prostaglandins – blood to kidney, suppressing acid in stomach, secretion of stomach mucus, produced constitutivelyCOX-2: only produced in response to inflammationCaused by cytokinesCOX-2 causes inflammation, feverMade antagonists for COX-2 (no inflammation, other processes still functioning)CelebrexVioxx (off market now)Block COX-2 onlyCOX-3Only in CNSNo effect on inflammationEnhances perception of pianCauses fever and headachesAcetaminophen – Tylenol; inhibits COX-BIOL 460 1st Edition Lecture 11Outline of Last Lecture I. Menstrual CycleII. Precursor Moleculesa. Prohormone b. Prehormone Outline of Current Lecture I. Priming Effecta. Upregulationb. Downregulationc. Paracrine regulationi. Prostaglandins ii. NSAIDSiii. Isoenzymes Current LecturePriming effect1. Can alter number of receptors in plasma membrane2. Upregulationa. Hypothalamus produces gonadotropin RHb. Initially has small effectc. Initial exposure causes upregulationd. Adenohypophysis makes more receptorse. Subsequent releases have more effect – similar to LTP3. Downregulationa. Target cells exposed to high concentrations of polypeptide hormones for a long timeb. Target cells begin removing receptorsc. Hormone has less effectd. To avoid down regulation – many polypeptide hormones are released in spurts – pulsatile secretione. Gonadotropin Releasing Hormone Agonisti. Drug that causes downregulationii. Helps with two conditions1. Benign prostatic hyperplasiaa. Enlarged prostateb. Less FSH/LHc. No testosteroned. No growth of prostate gland2. Endometriosis a. Some cells of stratum functionalis detach and


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