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BI 242 Environmental Science

BI 242 Environmental Science. Environmental Endocrine Disruptors (EDC’s) Dr. Joseph Colosi DeSales University. The Endocrine system. General Features of the endocrine system:. Transport. Gland. Hormone. Target Cell. rich blood supply. hormone receptors are very specific.

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BI 242 Environmental Science

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  1. BI 242 Environmental Science Environmental Endocrine Disruptors (EDC’s) Dr. Joseph Colosi DeSales University

  2. The Endocrine system General Features of the endocrine system: Transport Gland Hormone Target Cell rich blood supply hormone receptors are very specific secreted into the blood ductless can reach virtually every cell in the body C. Corbitt

  3. Endocrine Glands don’t forget the heart, placenta, fat All of these glands produce hormones and are also targets for hormones C. Coebitt

  4. Steroid hormones Insulin, a protein hormone

  5. There are many hormones Link to diagram showinglocations of the endocrine glandsThyroid-stimulating hormone (TSH)protein (201)Anterior lobe of pituitaryFollicle-stimulating hormone (FSH)protein (204)Luteinizing hormone (LH)protein (204)Prolactin (PRL)protein (198)Growth hormone (GH)protein (191)Adrenocorticotropic hormone (ACTH)peptide (39)Antidiuretic hormone (ADH)(vasopressin)peptide (9)Posterior lobe of pituitaryOxytocinpeptide (9)Thyrotropin-releasing hormone (TRH)peptide (3)HypothalamusGonadotropin-releasing hormone (GnRH)peptide (10)Growth hormone-releasing hormone (GHRH)peptides (40)Corticotropin-releasing hormone (CRH)peptide (41)Somatostatinpeptides (14, 28)DopamineTyrosine derivativeMelatoninTryptophan derivativePineal glandThyroxine (T4)Tyrosine derivativeThyroid GlandCalcitoninpeptide (32)Parathyroid hormone (PTH)protein (84)Parathyroid glandsGlucocorticoids (e.g., cortisol)steroidsAdrenal cortexMineralocorticoids (e.g., aldosterone)steroidsAndrogens (e.g., testosterone)steroidsAdrenaline (epinephrine)Tyrosine derivativeAdrenal medullaNoradrenaline (norepinephrine)Tyrosine derivativeEstrogens (e.g., estradiol)steroidOvarian follicleProgesteronesteroidCorpus luteum and placentaHuman chorionic gonadotropin (HCG)protein (237)Trophoblast and placentaAndrogens (e.g., testosterone)steroidTestesInsulinprotein (51)Pancreas (Islets of Langerhans)Glucagonpeptide (29)Somatostatinpeptides (14, 28)Amylinpeptide (37)Erythropoietin (EPO)protein (166)KidneyCalcitriolsteroid derivativeCalciferol (vitamin D3)steroid derivativeSkinAtrial-natriuretic peptide (ANP)peptides (28,32)HeartGastrinpeptides (14)Stomach and intestineSecretinpeptide (27)Cholecystokinin (CCK)peptides (8)Somatostatinpeptides (14,28)Neuropeptide Ypeptide (36)Ghrelinpeptide (28)PYY3-36peptide (34)Insulin-like growth factor-1 (IGF-1)protein (70)LiverAngiotensinogenproteinThrombopoietinprotein (332)LeptinproteinFat cellsNote (1): Numbers within parentheses indicate the number of amino acids in the protein or peptide(s).

  6. R R R G-protein Ion Enzyme channel effector Enzyme effector R Nuclear membrane R DNA binding sites Types of hormone receptors HORMONE Plasma Membrane Receptors Protein hormones Protein product Intracellular Receptors Steroid hormones NUCLEUS CELL MEMBRANE C. Corbitt

  7. - - - - - = negative feedback The H-P-G Axis HYPOTHALAMUS GnRH PITUITARY LH TESTIS Testosterone C. Corbitt

  8. It’s actually much more complicated C. corbitt

  9. Do exogenous hormones affect people?

  10. Diethylstilbestrol (DES) • 1938 Charles Dodds synthesized DES • 1941 Harvard: DES enhances pregnancy and prevents miscarriage • 1947 FDA Approved DES for pregnancy • 1947-1971 DES prescribed for 5 million US pregnant women, dose = 700 birth control pills • 1953 U of Chicago study: no DES miscarriage benefit

  11. Diethylstilbestrol (DES) • 1954 DES put in chicken and cattle feed • 1959 DES banned for chickens and lambs • 1964 Charles Dodds Knighted • 1971 Surgeon General warned against DES for pregnant women • 1979 USDA banned DES for cattle feed • 1970’s DES prescribed to many thousands of pregnant women throughout the world

  12. DES Outcomes(CDC DES page http://www.cdc.gov/des/consumers/) DES Daughters CDC DES daughter pagehttp://www.cdc.gov/des/consumers/about/effects_daughters.html • One third have reproductive tract abnormality • 100X greater risk for clear cell adenocarcinoma, from 0 to 1/1000 • 2.5X greater chance of miscarriage • 2 to 3X greater chance of ectopic pregnancy • 33% increase in infertility • 25% increase in premature delivery

  13. DES Outcomes(http://www.cdc.gov/des/consumers/) DES Sons • 4X increase in non-cancerous epidymal cysts • 3 to 4X increase in genital deformity? DES Grandchildren ?

  14. So avoid high doses of steroid drugs and you’ll be safe.

  15. USGS Water-quality survey, 1999-2000 Insect repellant First nationwide survey to detect 95 pharmaceuticals, hormones, and other organics in 139 urban and agricultural streams in 30 states. Two chemicals found in 80% of the samples, and 82 chemicals occurred in at least one sample. Flame retardant antibacterial surfactant surfactant Fungicide surfactant plasticizer Survey study 2002http://pubs.acs.org/hotartcl/est/es011055j_rev.html New study on pesticides 2006http://pubs.usgs.gov/fs/2006/3028/

  16. USGS Water-quality data, 1999-2000

  17. Detection limits for USGS study PPB PPT

  18. Compounds known to bind steroid receptors in humans and animalsRooney, AA, and LJ Gillette, Jr. Contaminant interactions with steroid receptors: evidence for receptor binding. In Guillette, LJ, Jr., and DA Crain. 2000 Environmental Endocrine Disrupters: An Evolutionary Perspective. Taylor and Francis. • Diethylstilbestrol (DES) Food contaminant • Butylated hydroxyanisole Food additive • Vinclozolin fungicide • Alachlor Herbicide • DDT Insecticide • P-Nonylphenol Industrial chemical • Genistein Phytoestrogen

  19. Compounds known to bind steroid receptorsRooney, AA, and LJ Gillette, Jr. Contaminant interactions with steroid receptors: evidence for receptor binding. In Guillette, LJ, Jr., and DA Crain. 2000 Environmental Endocrine Disrupters: An Evolutionary Perspective. Taylor and Francis.

  20. Every year, 5000 new chemical compounds are introduced. “Better living through chemistry.”

  21. How do these chemicals get into the environment?

  22. What it takes to be beautiful today. Where do these chemicals go when we shower and pee? Why pee?

  23. Bethlehem Sewage Treatment Plant

  24. Plastics R. Bolen

  25. Sheep feedlot Cattle feedlot

  26. Pesticides R. Bolen

  27. Industrial chemicals R. Bolen

  28. Do these chemicals in the environment affect wildlife?

  29. There are hundreds of research articles relating EDC’s to effects on wildlife: • feminization of male alligators, tadpoles • masculinization of female gastropods; female fish • impaired immune and decreased reproductive function in Baltic seals • eggshell thinning in water birds, eagles • all have resulted in population decline. R. Bolen

  30. Reproductive and developmental abnormalities attributed to endocrine disruption R. Bolen from McLachlan (2001)

  31. How Do Environmental EDC’s Work? McLachlan, J.A. 2001 Environmental Signaling: What Embryos and Evolution Teach Us About Endocrine Disrupting Chemicals, Endocrine Reviews 22(3): 319-341.

  32. Do these chemicals in the environment affect humans?

  33. Trends in human reproductive health • testicular dysgenesis syndrome • decreased semen quality (reduced numbers, motility, altered morphology of sperm) • increased frequency of male reproductive tract abnormalities • hypospadias (urinary tract opening located not at the tip of the penis) • cryptorchidism (testis fails to descend by age 12 months) • altered sex ratio (fewer male babies) • premature breast development (thelarche) • premature onset of menstruation (menarche) • increase in rates of breast cancer, testicular cancer Are these trends In humans caused by EDC’S? from Sharpe and Irvine (2004) R. Bolen

  34. What evidence links human reproductive problems to EDCs? • Girls exposed to higher levels of PBCs and DDE in utero entered puberty an average of 11 months earlier than controls • Higher levels of organochlorine chemicals found in mothers of men with testicular cancer • Exposure of boys to endosulfan associated with delayed puberty • Premature thelache in Puerto Rico associated with high blood phthalate levels. • Prenatal blood phthlate associated with feminization of male babies. R. Bolen

  35. 23-month-old Puerto Rican girl with premature thelarche Premature Thelarche Thelarche: breast development, timing depends on estrogen/androgen ratio Premature thelarche “epidemic” in Puerto Rico Premature Thelarche and Early Sexual Development Registry tracked 4,674 cases in P.R. since 1969 Several causes hypothesized: diet, EDCs Plasma phthalate ester levels correlated with premature thelarche cases Phthalate esters used as plasticizers; have estrogenic or anti-androgenic activity in vitro Colon, I, D Caro, CJ Bourdony, and O.Rosario. 2000. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ. Health Perspect. 108:895-900 But, McKee, RH. 2004. Phthalate exposure and early thelarche. Environ. Health Perspect. 112:A541-A543. Questions the results because the blood levels are too high and phthalates do not act like estrogens in female rodents C. Corbitt

  36. . August 2005 Environmental Health Perspectives 113: 1056-1061 penis Anogenital distance AGD anus AGI = AGD/weight

  37. What is EPA doing about it?

  38. EPA Screening protocols being tested http://www.epa.gov/scipoly/oscpendo/edspoverview/chronology.htm 1996-2005

  39. EPA will test for pesticide concentration in the the 20 most consumed foods for pesticides http://www.epa.gov/fedrgstr/EPA-TOX/2005/September/Day-27/t19260.pdf

  40. Current US regulations on environmental EDC’s • Banned: aldrin, chlordane, DDT, dieldrin, endrin, kepone, mirex, • PCB’s, toxaphene • Restricted: dicofol, dienochlor, endosulfan, heptachlor, lindane, • methoxychlor • Not regulated: Vast majority of EDC’s.

  41. Yeast Bioassay for Estrogenic CompoundsEstrogen-inducible expression system in yeast Sensitive to 10 PPT 17 -estradiol 1 part per trillion is one second in 32 thousand years. A playing card on a football field is one part per million. Cut the card into 1 million pieces. One of these pieces on a football field is one part per trillion. ONPG (Clear) Yellow Routledge, EI, JP Sumpter. 1996. Estrogenic activity of surfactants and some of their degradation products assessed using a recombinant yeast screen. Environmental Toxicology and Chemistry 15: 241-248

  42. PPB PPT

  43. Witters et al. (2001) Method for Extraction of Estrogenic Compounds from Wastewater Revised method - 0.2μm sterile filter 2.5 Liters of wastewater passed through 3 sets of filters (final pore size 0.45μm), then solid phase extraction disk. Estrogenic compounds eluted with acetone, dried with nitrogen, and dissolved in 100μl DMSO.

  44. Estrogenic compounds stimulate the yeast to convert the ONPG substrate into a yellow pigment. More yellow signifies more estrogenic compounds in the water.

  45. For further study: • What is the daily pattern of estrogenic chemicals in influent • wastewater? • What is the seasonal pattern? • Do these vary with source of wastewater? • How much is the concentration reduced by the treatment? Are • some treatments more effective? • Do the levels in the effluent affect aquatic wildlife? Terrestrial • wildlife? Humans?

  46. Summary • The endocrine system is complex and depends on extremely low • concentrations of hormones. • Many chemicals are found in US surface waters. • Many of these are EDC’s. • There are disturbing trends in sexual and devolpmental • dysfunction in wildlife and humans. • Progress on detection of EDC’s is slow. • Transgenic yeast has potential to expand our knowledge about the • occurrence of EDC’s.

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