1. The Endocrine System Pineal gland Hypothalamus Pituitary gland Thyroid
Parathyroid
gland
gland
Adrenal
glands
Pancreas
This is the first of a three-part lecture characterizing the toxicity, bioaccumulation, and persistence properties of environmental endocrine disruptors (EEDs). The characterization is primarily from a health risk assessment perspective. Therefore, the effects and properties so characterized are mainly those pertinent to exposure and risk significance, rather than those dealing with adverse health effects, of which endocrine disruption is an important type. The lecture’s overall objective is to convey the concept that even for a short duration, exposure to a persistent bioaccumulative EED of low disruption potency could lead to a severe health outcome.
To facilitate the characterization so promised, this Part I presents an overview of the human endocrine system and the basic mechanisms of endocrine disruption. It then concludes with a literature review to ascertain the effects of endocrine disruption as a major health problem.
Part II reviews the factors fundamental to a substance’s fate and bioaccumulation in the environment. Another effort of Part II is to provide some evidence from the literature on bioaccumulation and long-range transport. These literature data are intended to support the asseveration that many endocrine disruptors are highly bioaccumulative.
Part III brings forth the main themes of this lecture. It illustrates how and why endocrine disruption is inducible from exposure to a persistent bioaccumulant, even when its disruption potency is low and the exposure duration is short. Part III further elucidates the notion that at times, even induction of this kind could end with a severe health outcome.
Ovaries
Testicles
(women)
(men)

2. Endocrine System (I)
Cells, organs, and functions in the human or animal body are regulated practically every day by the endocrine system.
Structurally, the endocrine system is a collection of ductless glands that secrete chemical messages known as hormones.
Main function of the endocrine network is to maintain homeostasis of and long-term control in the body by means of chemical signals. It works in parallel with the nervous system to control many body functions.
The cells, the tissue organs, and the biological functions in the human or animal body are regulated or influenced practically every day by two anatomical and physiological systems. These are the nervous system and the endocrine system. The nervous system coordinates rapid and precise responses to stimuli through a momentary change in electrical potential in a cell or tissue. This momentary change occurs when a cell or tissue has been activated by a stimulus, and is commonly referred to as action potential. The functions performed by the nervous system are much more immediate and rapid, such as the control of breathing and body movement. Further discussion of this energy concept and the nervous system is beyond the scope of this lecture. Students with an interest in this subject area are referred to the basic textbooks on general physiology or neurophysiology.
The endocrine network, on the other hand, maintains homeostasis of and long-term control in our body by means of chemical signals. It works in parallel with the nervous system to control many body functions along with homeostasis. Homeostasis is a physiological term used to define a biological entity’s ability or tendency to maintain a steady internal state.
The endocrine system is a collection of ductless glands that secrete chemical messages which are commonly referred to as hormones. These signals are passed through the blood to arrive at target cells which possess the appropriate receptor, much like a lock of definite shape to which only one or certain keys can fit. Exocrine glands that secrete substances that are passed outside the body are ducted structures, such as digestive glands, sweat glands, and salivary glands. These ducted glands are thus by definition not part of the endocrine network.

3. Endocrine System (II)
The glands that make up the (human’s) endocrine system are hypothalamus, pituitary, thyroid, parathyroid, adrenals, pineal body, pancreas, ovaries, and testicles.
The primary function of these glands is to synthesize and secrete hormones.
Acting as body’s messengers, hormones transfer information and instructions from one set of cells to another; the shape of each hormone molecule is specific and can bind to certain cellular receptors only.
Unlike the nervous system, the endocrine system operates in a less rapid and more long-lasting manner. It is important to note that when the endocrine glands and the hormones that they secrete do not work properly, a variety of disorders can arise. Acting as the body’s messengers by transferring important information and instructions from one set of cells to another, hormones regulate the mood, body development, sexual function, pregnancy, other reproductive processes, and much more.
The glands that make up the (human’s) endocrine system are the hypothalamus, pituitary, thyroid, parathyroid, adrenals, pineal body, pancreas, ovaries, and testicles. Of note is that by anatomical design, part of the pancreas is exocrine, as its bulk is connected to the digestive system and secretes digestive enzymes into the intestine. Endocrine glands are not the only ones secreting hormones in our body. Some non-endocrine organs, such as the brain, heart, lungs, kidneys, liver, thymus, skin, and placenta, also produce (a small amount of) hormones.
The shape of each hormone molecule is specific and can bind to certain cells only. These unique binding sites on the target cells are called hormone receptors. Many hormones come in antagonistic pairs with opposite effects on the target organs. For example, glucagons and insulin have opposite effects on the liver’s control of sugar level in the blood. Insulin lowers the blood sugar levels by instructing the liver to take glucose out of circulation and store it, whereas glucagons instruct the liver to raise the blood sugar level by releasing some of the stored glucose. Many hormonal regulations depend on feedback loops to maintain balance and homeostasis.

4. Human Endocrine System major glands

5. Hypothalamus, Pituitary
The hypothalamus is located below the thalamus, in the lower center part of the brain; beneath this gland is the pituitary, which has the size of a pea. Together, these two glands control many other endocrine functions.
Hormones from the two glands are crucial to pregnancy, birth, lactation, and a woman’s menstrual cycle, including ovulation.
Growth hormone and antidiuretic hormone are also crucial hormones secreted by the anterior and posterior pituitary, respectively.
The hypothalamus is located in the lower center part of the brain, below the thalamus. This gland links the nervous system to the endocrine network by producing hormones capable of directing the anterior pituitary to release other hormones into the circulatory system. The pituitary gland, located at the base of the brain just beneath the hypothalamus, is no bigger than a pea. Together, these two glands control many other endocrine functions. The pituitary gland is often called the “master gland,” and is structurally divided into the anterior and the posterior lobe. The stimulation and the suppression of hormone secretions from this master gland are regulated by factors released by nerve cells (neurons) of the hypothalamus.
The several hormone products secreted by the hypothalamus and the pituitary are very crucial to pregnancy, birth, lactation, and the menstrual cycle. These include the follicle-stimulating hormone (FSH) and the leutinizing hormone (LH). FSH stimulates the maturation of ovarian follicles, of which only one contains a mature egg. The release of this mature egg is induced by a large burst of LH secretion by the pituitary gland. The amounts of FSH and LH in the body vary throughout the menstrual cycle, and are highest just before ovulation.
One critical hormone secreted by the anterior pituitary is growth hormone. Its major role is in stimulating the liver and other tissues to secrete the insulin-like growth factor IGF-1. This factor in turn is a major participant in the control of several complex physiologic processes, including growth and metabolism. Another important hormone, secreted by the posterior pituitary, is antidiuretic hormone (also known as vasopressin). The single most important role of this peptide hormone is in reducing the formation of urine to conserve body water.

6. (Para)Thyroid, Adrenals
Thyroid is located in the front and middle of the lower neck; thyroxine and T3 are two important hormones from this gland.
Located within each of the thyroid lobes are a pair of tiny oval-shaped glands called parathyroid; hormones from this gland are the most important regulator of serum calcium.
The two adrenals are each situated atop of each kidney; their corticosteroid and catechol-amine hormones play an important role in metabolism, the immune system, and stress.
The thyroid gland is located in the front and middle of the lower neck, below the larynx. It is shaped like a bow tie with two halves (lobes). Tetraiodothyronine (T4, or better known as thyroxine) and triiodothyronine (T3) are two major hormones of the thyroid gland. These two iodine-containing peptides control the rate at which cells burn body fuels from food to produce energy. Other thyroid hormones, such as calcitonin, also play a key role in bone growth and in the development of the brain and nervous system in children. In short, thyroid hormones are vital to many body functions, including heat production, heart rate, respiratory rate, and digestion. The release of thyroid hormones is controlled by the pituitary gland’s thyroid-stimulating hormone.
Located within each of the thyroid lobes are (usually) a pair of tiny oval-shaped glands that function together called the parathyroid glands. With the aid of calcitonin secreted by the thyroid, the parathyroid hormone secreted by these parathyroid glands is the most important endocrine regulator of calcium levels in the blood and in the extracellular fluid.
The two adrenal glands are triangular in shape, with each situated atop of each kidney. Each adrenal gland’s outer part is called adrenal cortex whereas its inner part, adrenal medulla. The adrenal cortex produces the corticosteroid hormones, which play an important role in metabolism, the immune system, certain aspects of behavior, and sexual function. These corticosteroids include aldosterone, hydrocortisone, and adrenal androgens. The adrenal medulla secretes norepinephrine and epinephrine to aid the body in dealing with stress. Both of these catecholamine hormones are associated with higher blood pressure and heart rate.

7. Pineal, Pancreas
The pineal body is located near the center of the brain, having the shape of a tiny clone; its hormone melatonin has significant effects on reproduction and daily physiologic cycles, most notably the circadian rhythms.
Pancreas has both exocrine and endocrine functions; its bulk is a ducted gland secreting digestive enzymes into the small intestine. Its endocrine function is by means of its many small clusters of endocrine cells, from which the hormones glucagons and insulin play an important role in regulating blood sugar level.
The pineal gland in humans is a clone-shaped structure of about 1 cm in length. It is located near the center of the brain. The pine clone-like organ consists of specialized secretory cells called pinealocytes, which synthesize the hormone melatonin and secrete it into the bloodstream by means of the surrounding cerebrospinal fluid. Melatonin has significant effects on reproduction and daily physiologic cycles, most notably the circadian rhythms.
Seasonal affective disorder (SAD) is a condition caused by the overproduction of melatonin, especially during the longer nights of winter. Its symptoms include tiredness, weight gain, sadness, profound depression, and oversleeping. Treatment of SAD thus should consist of exposure to bright lights for several hours each day to inhibit melatonin production. There is indication that melatonin plays a role in cancer inhibition (see Slide 19).
The pancreas has both exocrine and endocrine functions. The bulk of it is a ducted gland secreting digestive enzymes into the small intestine through the pancreatic duct. Its other function is achieved by means of its many small clusters of endocrine cells called islets of Langerhans. These islets consist of four types of cells called alpha, beta, delta, and gamma.
The alpha cells secrete glucagons, which mobilize glucose, fatty acids, and amino acids from stores into the blood in response to a low sugar level. The beta cells are responsible for the secretion of insulin which is needed to metabolize glucose. Patients are said to have diabetes mellitus if their pancreas does not make enough insulin to lower the blood sugar level, or if their muscle, fat, and liver cells do not respond to insulin’s normal function, or both.

8. Ovaries, Testicles
The female ovaries and the male testicles, responsible for many sex characteristics, are referred to as the gonad glands or sex organs.
Female ovaries synthesize the hormones estrogen and progesterone in varying amounts depending on where in her cycle a woman is.
Testicular production of the sex hormone testosterone (a principle androgen) begins during fetal development, continues for a short time after birth, nearly ceases during childhood, and then resumes at puberty.
The gonads are the female’s ovaries and the male’s testicles, or otherwise more commonly referred to as the sex (or sometimes also the reproductive) organs. In addition to producing gametes (ova and sperms), these sex organs secrete hormones. As mentioned earlier (Slide 8), the secretion of these sex hormones by the gonads is controlled by pituitary gland hormones such as the FSH (follicle-stimulating hormones) and LH (leutinizing hormones). While both sexes make some of each of these hormones, male testicles secrete primarily androgens of which testosterone is the principle one. Female ovaries make estrogens and progesterone in varying amounts depending on where in her cycle a woman is. In a pregnant woman, the baby’s placenta also secretes hormones to help maintain the pregnancy.
The estrogens and progesterone contribute substantially to the development and the function of female reproductive organs and sex characteristics. At the onset of puberty, estrogens promote several physiologic processes: distribution of fat evidenced in the hips, legs, and breast; development of the breasts; and maturation of reproductive organs such as the uterus and vagina. Progesterone causes the uterine lining to thicken in preparation for pregnancy.
Production of testosterone in males begins during fetal development, continues for a short time after birth, nearly ceases during childhood, and then resumes at puberty. This steroid hormone is responsible for several growth and sexually-related functions. These functions include but are not limited to: growth and development of the male reproductive structures; increased skeletal and muscular growth; enlargement of the larynx accompanied by voice changes; growth and distribution of body hair; and increased male sexual drive.

9. The endocrine system is regulated by feedback in much the same way that a thermostat regulates the temperature in a room. For the hormones that are regulated by the pituitary gland, a signal is sent from the hypothalamus to the pituitary gland in the form of a “releasing hormone,” which stimulates the pituitary to secrete a “stimulating hormone” into the circulation.
How does the Endocrine system work

10. Endocrine (continued)  The stimulating hormone then signals the target gland to secrete its hormone. As the level of this hormone rises in the circulation, the hypothalamus and the pituitary gland shut down secretion of the releasing hormone and the stimulating hormone, which in turn slows the secretion by the target gland. This system results in stable blood concentrations of the hormones that are regulated by the pituitary gland

11. Feedback control
Feedback control is a homeostasis mechanism used by the body to maintain a constant internal environment. If the brain receives impulses to communicate there is too much or too little of a substance, then impulses are sent to the relevant organs to return the situation to normal

12. How is feedback seen
Temperature control
Body fluids

13. Temperature control
Since the human body maintains a constant body temperature, therefore there must be ways in which the body adjusts its internal processes as the external temperature changes.