Endocrine system is disrupted by Environmental disruptors...how?
1. Any unwanted and undesired substances which contaminate or
deteriorate the quality of air, water and soil. These may directly
interact with environment after their indirect production in
various ways. These may be present in gaseous,liquid as well as
2. The endocrine system is a complex network of glands and
hormones that regulates many of the body's functions, including
growth, development and maturation, as well as the way various
organs operate. including the pituitary, thyroid, adrenal, thymus,
pancreas, ovaries, and testes release carefully-measured amounts of
hormones into the bloodstream that act as natural chemical
messengers, traveling to different parts of the body in order to
control and adjust many life functions.
3. An endocrine-disrupting substance is a compound, either
natural or synthetic which through environmental or inappropriate
developmental exposures alters the hormonal and homeostatic systems
that enable the organism to communicate with and respond to its
environment. The number of substances believed to act as endocrine
disruptors is wide and varied, including both natural and synthetic
materials. Concern arises because potential endocrine disruptors
may be present in the environment at very low levels but still may
be able to cause effects.
4. Endocrine disruptors are found also in synthetic chemicals
used as industrial solvents, lubricants, and their byproducts.
These include polychlorinated biphenyls (PCBs), polybrominated
biphenyls (PBBs), and dixons. bisphenol A (BPA) from plastics
dichlorodiphenyltrichloroethane (DDT) from pesticides vinclozolin
from fungizides diethylstilbestrol (DES) from pharmaceutical
agents. Certain metals such as cadmium, mercury, arsenic, lead,
manganese, and zinc also disrupt endocrine systems.s
5. They can mimic a natural hormone and lock onto a receptor
with in the cell. The disruptor may give a signal stronger than the
natural hormone, or a signal that occurs at the "wrong" time. They
can bind to a receptor within a cell and thus prevent the correct
hormone from binding. The normal signal then fails to occur and the
body fails to respond properly. The disruptors can interfere or
block the way natural hormones and receptors are made or
controlled. This interference or blockage may occur only if
relatively large doses of the substance are present.
6. A direct evidence of human susceptibility was found. In the
1950s and 1960s pregnant women were prescribed diethylstilbestrol
(DES), a synthetic estrogen, to prevent miscarriages Not only did
DES fail to prevent miscarriages, but it also caused health
problems for many of these women's children. In 1971, doctors began
reporting high rates of unusual vaginal cancers in teenage girls.
Investigations of the girls' environmental exposures traced the
problem to their mothers' use of DES. The girls also suffered birth
defects of the uterus and ovaries, and immune system
7. During normal conditions, a carrier protein transports
hormones to the cell wall; there, it binds to a receptor, and the
hormone and receptor together bind to a specific region of a cell's
DNA to activate particular genes.
8. EDCs interfere with this normal hormonal activity in number
of ways. They can amplify the effect of normal hormones by: 1.
Mimicking a hormone by binding to its receptor. 2. By stimulating
the production of more hormone receptors. They can weaker the
normal hormone functions by binding to its receptor.
9. They can prevent hormonal action simply by occupying the
appropriate hormone's site on the receptor. They can bind to
carrier proteins and reduce the availability of these proteins to
transport hormones . They can alter the level of endogenous
hormones by accelerating their breakdown and elimination.
10. Several possible modes of actions have been cleared up in
recent years, most important of them are mentioned here.
11. An exogenous agonist is a ligand that can bind to a
receptor like the natural substrate and turn it on. The potency of
an exogenous agonist depends on: Its affinity to the receptor Its
ability to turn the receptor on Concentration of the ligand
12. Well-known examples are: Diethylstilbestrol (DES)
Ethinylestradiol Xenoestrogens PCBs metabolites An antagonist is a
ligand that blocks or diminishes responses provoked by hormones
because the receptor cannot be activated as usual.
13. The inhibition of the receptor can be: Competitive that can
lead to total deactivation of the receptor. Noncompetitive that can
result in reduced reactions performed by the receptor. Well known
examples are: linuron vinclozolin pharmaceutical tamoxifen
14. Change in conc. of hormones indirectly i.e. by inhibiting
or influencing the specific enzymes. Examples: Biosynthesis of
estrogens include the conversion of testosterone to an estrogen
catalyzed by the enzyme aromatase. EDCs can inhibit this enzyme,
leading to higher testosterone concentrations and to lower estrogen
15. Hormone metabolism can also be influenced by induction of
hormone- metabolizing enzymes like the cytochrome P450-group in the
liver. In receptor-mediated processes, both components, endogenous
ligand and hormone receptor, own a key function.
16. Example Down-regulation of steroid hormones TCDD is an
exogenous agonist for the arylhydrocarbon (Ah)-receptor. Its
activation can have different influences on the endocrine system
by: (1) An increased degradation rate of estrogen receptors (2)
Induction of estradiol metabolizing enzymes (3) Inhibition of gene
expression controlled by estradiol or growth promoters.
17. Importance of Thyroid Harmones Thyroid hormones are
essential for: Normal brain development in fetus. For the control
of metabolism, For normal adult physiology.
18. Environmental pollutants Interfere with the normal
functioning of thyroid hormone and produce hazaderous effects on:
development metabolism adult physiology Disturbed Thyroid Harmone
19. Structural Similarity with THs: Several Thyroid Disruptors
have high degree of structural resemblance to the thyroxine (T4)
and triiodothyronine (T3) due to which they get attach to receptor
sites instead of THs. Interference with regulation: Many industrial
chemicals and pollutants can interfere with thyroid function by
acting on different points of regulation of thyroid hormone
synthesis, release, transport through the blood, metabolism of
20. Perchlorate It block uptake of Iodide(form of iodine) in
thyroid cells.As a result T3 and T4 synthesis decreased.Higher in
smoker Women. PCBs These are lipophilic in nature and accumulate in
fatty tissues.PCBs inhibit TSH receptors and decrease production of
T3 and T4. It reduce T4 circulation in blood. Acetochlor(Herbicide)
It enhance hepatic(liver) metabolism results in increase metabolism
of T3 and T4 unneccesarily
21. Pentachlorophenol T4 transport to target tissues via serum
transport proteins e.g Transthyretin(TTR) but if pentachlorophenol
competitively binds to serum transport proteins then T4 would not
be transported to target tissue. Bisphenol A(BPA) At high
temprature BPA leach out of plastics into food.
22. In Human embryonic kidney cell and hepatoblastoma cells BPA
inhibit T3 binding to TR . Isoflavones, especially those found in
soy protein (e.g., genistein, coumesterol) cause goiter in Human
23. Neurodevelopmental toxicity Goiter and thyroid diseases are
associated with TH disruption. Hypothyroidism It results in
impaired intellectual development in childrens or permanent
24. Perchlorate is a known competitive inhibitor of the
sodium-iodide in humans and can inhibit iodide uptake, leading to
the suppression of T3 and T4. Effects It has been related to lower
levels of iodine in breast milk.As a result of iodine deficiency
neurodevelopmental disorders occur in utero.
25. In an environment with perchlorate exposure may have a
significant effect on thyroid hormone production particularly in
the environment of dietary iodine insufficiency
26. The concept that PCBs can exert a neurotoxic effect on the
developing brain by causing a state of relative hypothyroidism.
Polychlorinated biphenyls belong to the class of organochlorine
compounds classified as persistent organohalogenated pollutants
(POPs) Disruption Mechanisms: (1)It reducing the ability of thyroid
hormones to bind to transport proteins in the bloodstream
27. (2)It enhance hepatic metabolism by up- regulating the
sulfotransferases that break down thyroid hormones in the liver
(3)It inhibit the production of deiodinases that allow T4 to be
converted to T3 (4)it act as either an agonist or antagonist at the
site of the cellular thyroid receptor.
29. The role of TSH in activating growth and differentiation of
follicular cells have shown that a prolonged disruption of the
pituitary-thyroid axis is linked to thyroid neoplasia. Two
mechanisms involved in the disruption of the pituitary thyroid axis
are chemically-induced blocking of thyroid peroxidase and
inhibition of T4 deiodinases, which are known to occur with TD
30. Humans are exposed to thousands of chemicals used in
several anthropogenic processes. Environmental factors that are
under the focus of the scientific community include organic and
chemical solvents, pesticides, heavy metals, polychlorinated
biphenyls (PCBs) and other persistent organic pollutants (POPs).
Among environmental pollutants, special concerns have been raised
by endocrine disrupting chemicals (EDCs), which are hormonally
active, synthetic or natural compounds that can interfere with the
normal activity of endocrine system/tissue, most notably the
reproductive endocrine axis. Human Reproductive Hormone Disruptors
31. 1. Adverse reproductive effects have been observed in male
populations, wildlife, and laboratory animals as a consequence of
exposure to hormonally active chemicals. 2. Chemicals could play a
role in a number of reproductive abnormalities in females. 3.
Endocrine disrupting chemicals could be contributing to a
population-wide decline in fertility. 4. Exposure to dioxins, toxic
byproducts of incineration and industrial processes, may be
associated with fewer male births. The hazardous effects
32. 5. Prenatal exposure to some chemicals is associated with
deficits in IQ and memory, neurobehavioral effects, and delayed
neuromuscular development in children. Examples: A.
Diethylstilbosterol (DES). B. Polychlorinated biphenyls (PCBs). C.
Polybrominated biphenyls (PBB). D. Chloroform. E. Dioxins and
furans. F. Pesticides
33. Diethylstilbosterol (DES): Consider one of the most famous
endocrine disruptors. A synthetic estrogen prescribed to pregnant
women in the 1950s and 1960s to prevent miscarriage. Ultimately,
more than 300 cases of CCA(clear cell endocarcinoma) have been
documented in women exposed in utero to DES. Polychlorinated
biphenyls (PCBs): Uses: paints. Lubricants Plastic water and baby
bottles, food and beverage can linings and dental sealants ate the
most commonly encountered uses of this chemical.
34. 1. The children born to these prenatally exposed mothers
have the following more than unexposed ones: 1. Sperm with abnormal
morphology, reduced motility, and reduced strength. 2. Intrauterine
growth retardation (IUGR). 3. Abnormal skin pigmentation. 4.
Delayed, developmental milestones. 5. Lower (IQs). 2. Women who had
eaten PCB-contaminated fish before and during pregnancy documented
dose- related delays in development and reductions in intellect in
their infants in the absence of any overt symptoms.
35. PESTICIDES: Reproductive effects: Effects on the
reproductive system or on the ability to produce healthy offspring.
Teratogenic: Causes birth defects if used it during their
pregnancy. The aberrant production of ovarian steroid hormones
(progesterone, estradiol, and androgens) can disrupt normal
folliculogenesis. It follows that environmental agents and
pathogens that mimic the actions of ovarian steroids via the
activation of steroid hormone receptors, could disrupt follicle
development and/or ovulation. Anti-androgenic endocrine disruptors:
36. Hazardous effects: Clear cell adenocarcinoma (CCA) of the
vagina and cervix . Irregular uterine bleeding. Recurrent abortion.
Intrauterine growth retardation. Abnormalities within the
reproductive, cardiovascular, neuroendocrine, and immune systems.
Effects on the ovary and female reproductive function:
37. BREAST CANCER A review of known risk factors includes the
possible influence of exogenous estrogens and several that are
related to levels of the naturally synthesized estrogen estradiol.
Early onset of menstruation, late menopause, never having given
birth and never having breastfed contribute to the risk by
elevating a woman's lifetime exposure to estradiol. Another risk
factor, being older than 50, probably reflects older women's
long-term exposure to this hormone. Additionally, the increased
odds of the disease that have been found among women with diets
high in animal fat and with high levels of alcohol consumption may
be explained by the fact that fat tissue can manufacture estrogen,
and alcohol can increase the hormone's production. These are not
the only risk factors for the disease (high-dose exposure to X rays
also plays an important role). Researchers hypothesize that if an
excess of natural estrogen can be harmful, prolonged exposure to
man- made estrogens might pose similar threats.
38. Eat lower on the food chain. Eat deep-water fish (avoid
sword fish, tuna and shark and all farm raised fish) In general,
substitute natural products for synthetic products whenever
possible. Eat fresh organic products as meat and milk free from
rBGH (Recombinant Bovine Growth Hormone). Buy products at your
local Farmers' Market or join a buying club. Use fewer processed,
prepackaged foods whenever possible. Do not give young children
soft plastic toys, since these leach potential endocrine disrupting
chemicals. Measures to lower the exposure to endocrine
39. Avoid smoke. Avoid use chemicals or any pesticides. Avoid
use makeup, hair sprays & coloring products or nail polish.
Avoid use strong chemicals, glues, paints, nail polish remover,
floor & carpet cleaners. Avoid heat food or eat hot food in
plastic containers, even the ones frozen dinners now come in. Avoid
products with hydrogenated, partially hydrogenated fats. Avoid stay
in places that smell of chemicals.