BIOL 460 1st Edition Lecture 11 Outline of Last Lecture I Menstrual Cycle II Precursor Molecules a Prohormone b Prehormone Outline of Current Lecture I Priming Effect a Upregulation b Downregulation c Paracrine regulation i Prostaglandins ii NSAIDS iii Isoenzymes Current Lecture Priming effect 1 Can alter number of receptors in plasma membrane 2 Upregulation a Hypothalamus produces gonadotropin RH b Initially has small effect c Initial exposure causes upregulation d Adenohypophysis makes more receptors e Subsequent releases have more effect similar to LTP 3 Downregulation a Target cells exposed to high concentrations of polypeptide hormones for a long time b Target cells begin removing receptors c Hormone has less effect d To avoid down regulation many polypeptide hormones are released in spurts pulsatile secretion e Gonadotropin Releasing Hormone Agonist i Drug that causes downregulation ii Helps with two conditions 1 Benign prostatic hyperplasia a Enlarged prostate b Less FSH LH c No testosterone d No growth of prostate gland 2 Endometriosis a Some cells of stratum functionalis detach and work their way into body cavity b FSH LH cause increase in cell division through estrogen c This can cause scarring and infertility 4 Paracrine Regulation a Signaling molecules released by cells in an organ that affect cells in the same b c d e organ Growth factors Cytokines produced by immune system Lymphokines cytokines made by lymphocyte Prostaglandins i Group of paracrine factors regulators 70 75 types ii Discovered by Ulf von Euler in human semen iii Thought they were produced by prostate gland iv Actually produced in all cells v Takes phospholipid from PM breaks down via phospholipase A2 producing arachidonic acid vi Arachidonic acid is an eicosanoid 20 carbons vii 2 enzymes 1 cyclooxygenase makes prostaglandins ecosanoid w five membered ring 2 Lipoxygenase leukotriene another PF causes asthma a Zyflo inhibits lipoxygenase b Singulair blocks glucotriene receptors viii Prostaglandin Effects 1 Often antagonistc 2 3 4 5 1 involved in blood clotting another prevents clotting some cause uterine contractions ovulation involved in immune system fever development pain in gastrointestinal tract block acid secretion produce protective mucus 6 blood supply to kidneys causes adequate supply ix NSAIDS non steroidal anti inflammatory drugs 1 Aspirin 2 Ibuprofen Motrin 3 Aleve 4 Inhibit all isoenzymes equally 5 Inhibit cyclooxygenase 6 Long term use causes harsh side effects such as gastric ulcers 7 Can eventually cause kidney failure x 3 Isoenzymes of cyclooxygenase 1 COX 1 important prostaglandins blood to kidney suppressing acid in stomach secretion of stomach mucus produced constitutively 2 COX 2 only produced in response to inflammation a Caused by cytokines b COX 2 causes inflammation fever c Made antagonists for COX 2 no inflammation other processes still functioning i Celebrex ii Vioxx off market now iii Block COX 2 only 3 COX 3 a b c d e Only in CNS No effect on inflammation Enhances perception of pain Causes fever and headaches Acetaminophen Tylenol inhibits COX 3 Priming effect Can alter number of receptors in plasma membrane Upregulation o Hypothalamus produces gonadotropin RH o Initially has small effect o Initial exposure causes upregulation o Adenohypophysis makes more receptors o Subsequent releases have more effect similar to LTP Downregulation o Target cells exposed to high concentrations of polypeptide hormones for along time o Target cells begin removing receptors o Hormone has less effect o To avoid down regulation many polypeptide hormones are released in spurts pulsatile secretion o Gonadotropin Releasing Hormone Agonist Drug that causes downregulation Helps with two conditions Benign prostatic hyperplasia Enlarged prostate Less FSH LH No testosterone No growth of prostate gland Endometriosis Some cells of stratum functionalis detach and work their way into body cavity FSH LH cause increase in cell division through estrogen This can cause scarring and infertility Paracrine Regulation o Signaling molecules released by cells in an organ that affect cells in the same organ o Growth factors o Cytokines produced by immune system o Lymphokines cytokines made by lymphocyte o Prostaglandins Group of paracrine factors regulators 70 75 types Discovered by Ulf von Euler in human semen Thought they were produced by prostate gland Actually produced in all cells Takes phospholipid from PM breaks down via phospholipase A2 producing arachidonic acid Arachidonic acid is an eicosanoid 20 carbons 2 enzymes cyclooxygenase makes prostaglandins ecosanoid w five membered ring Lipoxygenase leukotriene another PF causes asthma Zyflo inhibits lipoxygenase Singulair blocks glucotriene receptors Prostaglandin Effects Often antagonistc 1 involved in blood clotting another prevents clotting some cause uterine contractions ovulation involved in immune system fever development pain in gastrointestinal tract block acid secretion produce protective mucus blood supply to kidneys causes adequate supply NSAIDS non steroidal anti inflammatory drugs Aspirin Ibuprofen motrin Aleve Inhibit all isoenzymes equally Inhibit cyclooxygenase Long term use causes harsh side effects such as gastric ulcers Can eventually cause kidney failure 3 Isoenzymes of cyclooxygenase COX 1 important prostaglandins blood to kidney suppressing acid in stomach secretion of stomach mucus produced constitutively COX 2 only produced in response to inflammation Caused by cytokines COX 2 causes inflammation fever Made antagonists for COX 2 no inflammation other processes still functioning o Celebrex o Vioxx off market now o Block COX 2 only COX 3 Only in CNS No effect on inflammation Enhances perception of pian Causes fever and headaches Acetaminophen Tylenol inhibits COX 3 Priming effect Can alter number of receptors in plasma membrane Upregulation Hypothalamus produces gonadotropin RH Initially has small effect Initial exposure causes upregulation Adenohypophysis makes more receptors Subsequent releases have more effect similar to LTP Downregulation Target cells exposed to high concentrations of polypeptide hormones for along time Target cells begin removing receptors Hormone has less effect To avoid down regulation many polypeptide hormones are released in spurts pulsatile secretion Gonadotropin Releasing Hormone Agonist Drug that causes downregulation Helps with two conditions Benign prostatic hyperplasia Enlarged prostate Less FSH LH No