| Endocrine Disruptors |
| Organizational and Activational Effects | |
| What is an Endocrine Disruptor? |
| Natural chemical (phytochemical) | |
| Synthetic chemical (xenobiotic) | |
| Enters body | |
| Disrupts normal endocrine events |
| Where are EDs Found? |
| Plants: | ||
| Human-made | ||
| Plastics | ||
| Drugs | ||
| Household products | ||
| Industrial chemicals | ||
| Pesticides | ||
| Slide 4 |
| Slide 5 |
| Mechanisms of Action |
| Bind steroid hormone receptors and mimic | |
| Block hormone binding | |
| Alter cell-signaling & gene expression without binding | |
| Influence production or metabolism of hormones | |
| Influence hormone receptor production or action | |
| Influence enzyme-related hormone functions |
| Most EDs |
| Estrogenic | |
| Androgenic | |
| Anti-androgenic |
| Slide 8 |
| Slide 9 |
| Slide 10 |
| Slide 11 |
| Cell Signaling |
| Not fully understood | ||
| DDT | ||
| Estrogenic effects--unknown pathway | ||
| Direct binding with androgen receptors | ||
| Hypothalamic-Pituitary-Gonadal Axis |
| Organizational and Activational Hypothesis |
| Reproductive organs are organized and formed during the larval period with the help of steroid hormones. | |
| These organs are later activated during the organismÕs reproductive period by the same hormones that organized these structures. |
| Slide 15 |
| About Steroid HormonesÉ |
| Small amounts = potent effects | |
| Travel with carrier proteins | |
| Bind cytoplasmic or nuclear receptors | |
| Exert genomic effects | |
| Organization and Activation |
| How are EDs different or similar? |
| A little goes a long way | |
| bioavailability b/c no need for carrier | |
| Can exert more than one effect | |
| Hand-me-down toxin |
| ED Target Tissues |
| Organs with gonadal hormone receptors | |
| Females = mammary glands, reproductive tract | |
| Males = reproductive tract | |
| Both sexes = external genitalia, brain, skeleton, thyroid, liver, kidney, and immune system |
| Slide 19 |
| Slide 20 |
| Slide 21 |
| Slide 22 |
| Effects |
| Permanent if organizational | |
| Morphological | |
| Behavioral | |
| Immunological | |
| ø Stress response |
| The ED Timeline |
| A ÒSilentÓ Omen |
| Rachel Carson | |
| 1907-1964 | |
| Silent Spring (1962) | |
| Over-use of pesticides | |
| DDT (1945) | |
| DDT ban 1972 | |
| Slide 26 |
| Slide 27 |
| Theo Colborn |
| WWF scientist | |
| BS 1947 Rutgers | |
| PhD 1985 UW Mad. | |
| Studied Great Lakes | |
| 1991 EDs | |
| Our Stolen Future 1996 | |
| Combines human and animal research on EDs | |
| Explosion of ED research | |
| Reptiles and Amphibians |
| Slide 30 |
| Slide 31 |
| Slide 32 |
| Amphibian Work |
| Reeder et al. 1998, Rania 1998 |
| ÒÉhalf the manÓ |
| Lou Guillette 1993 | |
| Lake Apopka and Tower Chemical 1980 | |
| Alligator infertility 1994 | |
| Lake Apopka Gators |
| Circulating sex hormone levels with RIA | |||
| Females = low E2 | |||
| Males = low T | |||
| High E2 in testes | |||
| Pesticides with GC | |||
| Water Snakes and Coal Ash |
| EDs in prey items | ||
| Affect liver | ||
| Hopkins (2000) | ||
| Ganser et al. (2003) | ||
| Trace elements | ||
| Selenium | ||
| Arsenic | ||
| (Mercury) | ||
| Slide 38 |
| Slide 39 |
| Slide 40 |
| Slide 41 |
| Slide 42 |
| Organizational Effects |
| Most prevalent | |
| Permanent | |
| Larvae and adults | |
| Affect morphology | |
| Behavior (shore birds) | |
| Reproductive success | |
| Populations |
| Activational Effects |
| Affect receptor populations | |
| Affect receptor binding | |
| Slide 45 |
| Study Points Not Limited ToÉ |
| Types (classes) of hormones | |
| Endocrine vs. Exocrine Glands | |
| Feedback Loops | |
| Interaction between hypothalamus and pituitary gland | |
| Specific hormonal problems--be able to identify feedback anomalies | |
| Disruptors vs. Natural Hormones | |
| Organizational Activational Hypothesis |
| Be a Physiological Detective |
| Pinpoint problem area in feedback loop | |
| Predict effects | |
| What symptoms might you look for? | |
| See if you can solve the following problems: |
| Thyroid Storm |
| Patient presents with: | ||
| Hypermetabolism | ||
| Fever | ||
| Rapid heart rate | ||
| Irritability | ||
| Exopthalmia | ||
| Serum TH levels are high | ||
| Where is the problem in the feedback loop? | ||
| Which organ would you treat to stop the loop? | ||
| Birthday |
| A pregnant woman surpasses her due date. | |
| She presents at the emergency room without any physical symptoms besides a decreased amount of fetal movement. | |
| Though the baby is not too distressed, you feel you must deliver the baby | |
| What can you do? |
| Swollen Neck Glands |
| Your patient is a visitor from a different country. | |
| She presents with a palpable mass lateral to her trachea. | |
| She complains of feeling cold and sluggish | |
| In her patient history, you find that her diet is low in iodine. | |
| Where is the problem in the feedback loop? |
| Slide 51 |
| Slide 52 |