Hormones and Endocrine Disruptors Quiz

Teaching Philosophy

• Professor Banu aims to create a stress-free learning environment where students feel comfortable, supported, and free to interact with joy, curiosity, and passion.
• The professor believes that this type of classroom environment dramatically impacts students' learning interests, performance, interaction, and the outcome of their overall learning in a positive way.
• Aims to foster students' self-esteem, and help each student feel their own values, uniqueness, and talents.
• A key point is to break the stranger anxiety between the students and the teacher.
• The professor said she is available for students as long as they need her, and she makes herself easily approachable.
• When interacting with students, the professor views, addresses, approaches, and interacts with students as the future leaders, physicians, directors, presidents, and researchers.
• This approach increases learning ability and raises the bar above the average learning curve.
• Strives to foster curiosity and enthusiasm in students for learning by designing the course in an engaging way.
• Focus is on teaching the materials and exploring related information, and interacting with the other students about the new information that they learn.
• The professor understands this is a challenging course; however, students seem to appreciate learning about exposure to these harmful chemicals and how to avoid them in their daily lives, thus making healthy lifestyle choices and sharing what they learn with their family and friends.

Endocrine Organs

• Hypothalamus
• Pituitary
• Pineal
• Thyroid
• Parathyroid
• Thymus
• Adrenal
• Kidney
• Pancreas
• Ovary
• Uterus
• Testes

Endocrine Disruptors and Hormone Mimicry

• Thyroid gland & hormone are mimicked by PCBs
• Ovaries & Estrogen are mimicked by BPAs
• Testis & Testosterone is antagonized by Atrazine

Types of Hormones

• Endocrine hormones travel through the blood: examples are steroid and thyroid hormones.
• Paracrine hormones act on nearby cells
• Autocrine hormones act on themself: cytokines
• Neurocrine hormones are secreted by neural cells (neurotransmitters and neurohormones)

Examples of Neurotransmitters and Neurohormones

• Examples of neurotransmitters; glutamate, aspartate, D-serine, GABA, and glycine
• Examples of monoamines; dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline), histamine, and serotonin (SER, 5-HT).
• Examples of neurohormones; oxytocin and antidiuretic hormone (also referred to as vasopressin).

Amine Hormones

• Amine Hormones are derived from the amino acid tyrosine.
• Includes thyroid hormones and catecholamines (chromaffin cells of the adrenal medulla)
• Stored until secreted in the body

Steroid Hormones

• Made from cholesterol, are lipophilic (dissolve in fats) and can enter target cells
• Immediately released from the cells after synthesis
• Interact with cytoplasmic or nuclear receptors
• Activate DNA for protein synthesis
• Slower acting and have a longer half-life than peptide hormones
• Examples: cortisol, estrogen & testosterone

Steroid Hormone Actions

• Hydrophobic steroids bind to plasma protein carriers and only hormone unbound can diffuse into the target cell steroid hormone receptors are in the cytoplasm or nucleus
• The receptor-hormone complex binds to DNA and activates or represses genes
• Activated genes create new mRNA which moves back to the cytoplasm
• This translation produces new proteins used for important cell processes
• Some steroid hormones also bind to cell receptors that use 2nd messenger systems which creates fast cell responses

Endocrine Disruptors Introduction

• Endocrine disruptors are synthetic chemicals, or natural phytoestrogens, that affect the endocrine systems of humans and animals.
• They mimic, block, or interfere with the natural instructions of hormones to cells.
• Classes of EDCs include heavy metals, combustion by-products, pharmaceuticals (like DES), pesticides (like DDT, dieldrin, and endosulfan), plasticizers (like DEHP, phthalates, and BPA), flame retardants (PBDEs), detergents, and persistent organochlorines (PCBs, dioxins, and furans).

Definitions of Endocrine Disruptors

• 1996 EPA Definition: An exogenous agent that interferes with production, release, transport, metabolism, binding, action, or elimination of natural hormones responsible for homeostasis and developmental regulation
• 1996 EU Definition: An exogenous substance causing adverse health effects in an intact organism or its progeny, secondary to endocrine function changes. Potential EDCs possesses properties expected to cause endocrine disruption in an intact organism.
• 2002 WHO/IPCS Definition: An exogenous substance or mixture altering endocrine system function(s), causing adverse effects in an intact organism, its progeny, or (sub)populations.
• 2012 Endocrine Society Definition: An exogenous chemical or mixture interfering with hormone action aspects.

Common Sources of EDCs

• Sources include industrial processes, steel foundries, motor vehicles, PVC incinerators, building fires, cigarette smoke, pesticides, fungicides, cosmetics, and sunscreens.

EDCs in Everyday Use

• Common sources of EDCs include pharmaceuticals (birth control pills), dental sealants, solvents, surfactants, pesticides (Roundup), and some plastics.
• EDCs have a large variety of molecular features and potency, and the effect of potency depends on target organ/cells
• EDC’s mimic naturally found hormones to potentially cause overstimulation
• Bind to a receptor to block the hormone from binding, leads to interferences with natural hormone metabolism in the liver.

EDC Accumulation and Action

• Some toxicants, like EDCs, can be excreted or metabolized while others are stored in the body's fatty tissues.
• Fat-soluble toxicants are stored in fatty tissues
• Bioaccumulation = toxicants build up in animal tissues
• Biomagnification=toxicants concentrate in top predators
• Humans are at the top so will have the highest level of EDCs

Dangers to Fetus

• EDCs can cross the placenta into the fetus.
• EDCs can be passed down to the infants through their mother’s milk
• Combinations of 2 or more chemicals can cause the toxicity levels to rise
• Combinations of weak environmental estrogens, such as dieldrin and endosulfan are 1000x as strong as each one separately

How EDCs work in the cell

• EDCs mimic the chemical structure of hormones to bind with estrogen receptors

EDC Effects on Wildlife

• Mammals, birds, fish, amphibians, and reptiles are all impacted by EDCs
• Impactful EDCs- Mercury, PCBs
• Common outcomes- Sterility, tumor growth and decreased testosterone
• TCDD is another name for dioxin
• Vitellogenin, a precursor protein of egg yolk, present only in females, is a biomarker of exposure to environmental estrogens in vertebrates.

Sources of Human EDC Exposure

• Poly Vinyl Chloride (PVC) is responsible for the greatest level of Edc exposure
• PVC is toxic when produced, used and disposed of
• Found in toys, clothing, water pipes, raincoats and medical supplies
• Dioxin produced from PVC manufacturing
• BPA (Bisphenol-A) is common in PVC and leaks into liquid and greasy foods.
• Flexible PVC products - 95% of phthalates are used in PVC to function as half the products weight!

EDC Health Outcomes

• Heating foods in the microwave using plastic = dioxins produced
• Dioxins are a carcinogen and highly toxic, with half life of 8.5 years in the human body
• Some symptoms from EDC exposure include neurological damage, dermal and ocular lesions, irregular menstrual cycles and decreased immune response

Specific examples EDCs

• Some common classes of chemicals and examples are:
  • Plasticizers: Bisphenol-A is the most common
• Polystyrene: Used for food packaging, may leach Styrene
• Pesticides: Americans use ~2 billion pounds/year, and some are endocrine disruptors that stay in the food chain for decades -DDT in particular can cause congenital malformations, decreased sperm count, and increases in breast cancer.
• Herbicides: one example is Atrazine(ATZ)
  • ~75 million lbs are used each year in the US
  • Can run off into rivers and groundwater at toxic levels and contaminate drinking water
  • Inhibits production of testosterone and causes chemical castrations, causing the feminization of males
    • Northern Leopard Frogs, for example, have been found to have eggs growing in their testicles Birth defects: alterations in sexual and functional development, neurologic disorders, diabetes mellitus, immunologic disorders, early puberty in young girls
• Cancers: breast, colon, vaginal, endometriosis, cervix, testicular; sexual differentiation of the brain and other estrogen target tissues, structural abnormalities of the oviduct, uterus, cervix and vagina, a contributing factor to subfertility

Dirty Dozen EDCs

• BPA: Linked to cancer and reproductive/heart problems, found in 93% Americans
• Dioxin: disrupt hormone signaling, powerful carcinogens. Found in butter, meat, milk, seafood and eggs
• Atrazine: in most water crops, pervasive in drinking H20 - delayed puberty + prostate inflammation = prostate cancer
• Phthalates: hormone changes/lower sperm count - male reproductive defects, also with obesity and thyroid irregularities
• Perchlorate: compete with iodine and disrupts thyroid hormone development
• Fire retardants: Immitate the functions of thyroid hormones and can lower humans IQ levels
• Lead and Arsenic: damages organ systems can cause cancer, skin problems + weight and hormone malfunction
• Mercury: contaminates seafood, can deregulate cycle and interfere with pregnancy
• PFCs:  link to decreased sperm quality, thyroid disease and high cholesterol, among other health issues
• Organophosphate pesticides and Glycol Ethers

How to Reduce EDC Exposure

• Avoid strong chemicals, glues, paints, nail/carpet polish.
• Don't heat food/eat hot food in plastic containers.
• Purchase organic produce, meats and milk
• Buy local produce, lower food the chain, avoid canned goods, spend less time in places that smell of chemicals