Endocrine Disrupting Chemicals EDCs Prof Lata Bhattachary HOD

Endocrine Disrupting Chemicals (EDCs) Prof. Lata Bhattachary HOD, Coordinator, B. Sc. (Hons. ) Biotech and Dean (Life Science) School of Studies In Zoology and Biotechnology Vikram, University, Ujjain

Exposures to known EDCs are relatively high in contaminated environments in which industrial chemicals leach into soil and water; are taken up by microorganisms, algae, and plants; and move into the animal kingdom as animals eat the plants, and bigger animals eat the smaller animals. Animals at the top of the food chain, including humans, have the highest concentrations of such environmental chemicals in their tissues. This is also known as Bio-magnification or Bioaccumulation Increasing chemical production and use is related to the growing incidence of endocrine-associated pediatric disorders over the past 20 years, including male reproductive problems (cryptorchidism, hypospadias, testicular cancer), early female puberty, leukemia, brain cancer, and neurobehavioral disorders.

WHAT ARE EDCs, HOW ARE THEY USED, AND WHERE ARE THEY FOUND? EDCs were recently defined by the Endocrine Society (endocrine. org), the largest international group of scientists and physicians working and practicing in the field of endocrinology, as: “an exogenous [non-natural] chemical, or mixture of chemicals, that interferes with any aspect of hormone action” (5). There are over 85, 000 manufactured chemicals, of which thousands may be EDCs. A short list of representative EDCs and their applications is provided in Table 2. There are dozens of other processes and products that include EDCs, too numerous to include in this table.

BACKGROUND ON THE HUMAN ENDOCRINE SYSTEM The endocrine system consists of a series of glands that are distributed throughout the body. Each gland produces one or more hormones. Hormones are natural chemicals that are produced in cells within a gland released into the circulatory system, where they travel through the bloodstream until they reach a target tissue or organ. There, they bind to specific receptors, triggering a response such as production of another hormone, a change in metabolism, a behavioral response, or other responses, depending upon the specific hormone and its target. Some endocrine glands produce a single hormone, while others produce multiple endocrine hormones. For example, the parathyroid gland produces a single known hormone (parathyroid hormone), whereas the pituitary gland makes eight or more hormones, including prolactin and growth hormone. Prolactin is involved in making breast milk, and it is only synthesized and released from the pituitary glands of women who are breast feeding their infants. By contrast, growth hormone is synthesized throughout life, as it is important for growth and development in childhood and for building and maintaining muscles and the skeleton in adulthood. It is also notable that some endocrine glands have other, non-endocrine functions. The pancreas is a good example: it produces the hormone insulin, which circulates in the blood and is necessary for normal regulation of blood sugar levels; and it makes digestive enzymes that go directly to the digestive tract and are not part of the endocrine system because they are not released into the blood.

Clearly, endocrine systems and functions are complex and diverse, with each gland hormone playing unique roles in health and well-being. Because of the endocrine system’s critical role in so many important biological and physiological functions, impairments in any part of the endocrine system can lead to disease or even death. For example: Ø Diabetics have deficiencies in insulin release and/or action, and people with type I diabetes will die without insulin replacement. Ø Aldosterone is also critical for life, and adrenal diseases affecting aldosterone function can be life-threatening. Ø Over-secretion of hormones such as thyroid hormone results in metabolic disturbances and many physical and neurobiological changes, due to thyroid hormone’s key role in day-to-day cellular metabolism and brain function. Ø Other hormonal dysfunctions include infertility, growth disturbances, sleep disorders, and many other chronic and acute diseases. ØThus, endocrine hormones must be released at the appropriate amounts, and endocrine glands must be able to adjust hormone release in response to the changing environment, to enable a healthy life.

• Hormones are chemical signals. · The endocrine system consists of: · Endocrine cells which are hormone-secreting cells and · Endocrine glands which are hormonesecreting organs. • Specific target cells respond to specific hormones.

• Homeostasis • Growth and Development • Reproduction • Energy Metabolism • Behavior

blood glucose low glucose release from liver stimulates glucagon from stimulates pancreas blood glucose high inhibits

response endocrine cell hormones receptor protein target cell

response endocrine cell hormones intracellular target receptor cell

Tropic hormones- stimulate the production and secretion of hormones by other endocrine glands; ex. TSH Nontropic hormones- stimulates cellular growth, metabolism, or other functions; ex. thyroxine

Major endocrine glands: Hypothalamus Pineal gland Pituitary gland Thyroid gland Parathyroid glands Organs containing endocrine cells: Thymus Heart Adrenal glands Testes Liver Stomach Pancreas Kidney Small intestine Ovaries

pineal gland hypothalamus pituitary gland

Produces melatonin (synthesized from seratonin, a derivative of tryptophan) • Secreted directly in CSF to blood • High levels at night make us sleepy; low level during day • Pineal gland is stimulated by darkness and inhibited by light • Function in regulating circadian rhythms (sleep, body temp, appetite) biological clock

hypothalamus anterior pituitary posterior pituitary

Hypothalamus Posterior Pituitary Anterior Pituitary

Antidiuretic Hormone (ADH) Oxytocin (+ feedback)

Hypothalamus Posterior Pituitary Anterior Pituitary

• Growth Hormone (GH) - Dwarfism - Gigantism & Acromegaly • Thyroid Stimulating Hormone (TSH) • Adrenocorticotropic Hormone (ACTH) • Gonadotropins (FSH, ICSH, LH) • Prolactin (PRL) • Melanocyte-stimulating Hormone (MSH)

• Acts on the liver, stimulating it to release several polypeptide hormones. • Stimulates amino acid uptake and protein synthesis in target cells. • Ultimately stimulates cell growth (cell size and number), especially in muscle and bone. • Also stimulates fat breakdown.

GH Levels awake strenuous exercise sleep

Dwarfism hyposecretion of GH Kenadie - worlds smallest girl due to primordial dwarfism Little People Big World

Gigantism Hypersecretion of GH Bao Xishun, a 7 ft 8. 95 in herdsman from Inner Mongolia

Acromegaly hypersecretion of GH 7 ft 1 ¼ inches

Thyroid-Stimulating Hormone (TSH) • Acts on the thyroid gland, stimulating it to release T 3 & T 4 • These thyroid hormones increase glucose catabolism and body heat production. • Negative feedback mechanism involved in regulating levels.

Adrenocorticotropic Hormone (ACTH) • Acts on the adrenal cortex, stimulating it to secrete glucocorticoids (e. g. , cortisol). • Glucocorticoids promote the synthesis of glucose from noncarbohydrate sources such as amino acids, and fatty acids • Negative feedback mechanism involved in regulating levels.

larynx thyroid trachea

Thyroid gland selectively uptakes iodine to produce T 3 & T 4 • Thyroxine (T 4) • Triiodothyronine (T 3) Both control metabolic rate and cellular oxidation • Calcitonin (from parafolicular cells)- lowers blood CA ++ levels and causes CA++ reabsorption in bone

Thyroid Hormone Regulation

Thyroid Disorders - Hyperthyroidism (Grave’s, Goiter) - Hypothyroidism (Cretinism, Myxedima)

Goiter Lack of iodine in diet hyposecretion of T 3 & T 4

Cretinism hyposecretion of T 3 & T 4

Myxedema hyposecretion of T 3 & T 4 myxedema After thyroid treatment

Exophthalmos- hyperthyroidism

PTH release: 1) stimulates osteoclasts 2) enhances reabsorption of Ca++ by kidneys 3) increases absorption of Ca++ by intestinal mucosal cells Hyperparathyroidism- too much Ca++ drawn out of bone; could be due to tumor Hypoparathyroidism- most often follow parathyroid gland trauma or after removal of thyroid--- tetany, muscle twitches, convulsions; if untreated respiratory paralysis and death

• Regulates glucose uptake by cells • Controlled via negative feedback: insulin & glucagon • Blood sugar level: 90 mg/m. L

• Produced by the cells of the Islets of Langerhan • Catalyze oxidation of glucose for ATP production • Lowers blood glucose levels by promoting transport of glucose into cells. • Stimulates glucose uptake by the liver and muscle cells. • Stimulates glycogen synthesis in the liver and muscle cells. • Also stimulates amino acid uptake and protein synthesis of muscle tissue

• Produced by the cells of the Islets of Langerhans • Stimulates change of glycogen to glucose in the liver. • Synthesis of glucose from lactic acid and non carbohydrate molecules such as fatty acids and amino acids • Causes in blood glucose concentration hypoglycemic- low blood sugar ; deficient in glucagon

Type I Diabetes hyposecretion of insulin dependant juvenile onset Type II Diabetes late onset (adult) insensitivity of cells to insulin manage by exercise & diet

Adrenal Glands adrenal cortex adrenal medulla

Hormones of the Adrenal Medulla • Adrenalin (epinephrine): converts glycogen to glucose in liver • Noradrenalin (norepinephrine): increases blood pressure (sympathetic nervous system) • Corticosteroids: glucose levels)

Hormones of the Adrenal Cortex Glucocorticoids- cortisol 1. Decrease protein synthesis 2. Increase release and use of fatty acids 3. Stimulates the liver to produce glucose from non carb’s Mineralcorticoids- aldosterone 1. Stimulates cells in kidney to reabsorb Na+ from filtrate 2. Increases water reabsorption in kidneys 3. Increases blood pressure Sex Steroids- small amts (androgens) 1. Onset of puberty 2. Sex drive

Cushing’s Syndrome Hypersecretion of cortisone; may be caused by an ACTH releasing tumor in pituitary Symptoms: trunkal obesity and moon face, emotional instability Treatment: removal of adrenal gland hormone replacement

Addison’s Disease Hyposecretion of glucocorticoids and mineral corticoids; Symptoms- wt loss, fatigue, dizziness, changes in mood and personality, low levels of plasma glucose and Na+ levels, high levels of K+ Treatment- corticosteroid replacement therapy

Thymus Located anterior to the heart Produces- thymopoetin and thymosin helps direct maturation and specialization of T-lymphocytes (immunity)

Gonads Ovaries- produce estrogen and progesterone responsible for maturation of the reproductive organs and 2 ndary sex characteristics in girls at puberty

Female Reproductive System

Gonads Testes- produce sperm and testosterone (initiates maturation of male repro organs and 2 ndary sex characteristics in boys at puberty)

Male Reproductive System

Homeostatic imbalances • Hypothyroidism results – Myxedema (in adults) – Goiter—low levels of iodine – Cretinism (in children) • Hyperthyroidism results – Graves disease

Adrenal Cortex Imbalances • Hypersecretion leads to Cushing’s disease – ACTH-releasing tumors or side effects of corticoid drugs. • Hyposecretion leads to Addison’s Disease – Deficits in glucocorticoids and mineralcorticoids

endocrine-disrupting chemicals (EDCs)