# Structural Biochemistry/Cell Signaling Pathways/Endocrine Signaling

The word endocrine is actually from the Greeks and the endo definition means "within" and krine definition means "to separate or to secrete." The term endocrine means “secreting internally,” and specifically refers to secretions that are distributed in the body by way of the bloodstream. Endocrine cells are made up of ductless glands that produce chemical messages called hormones, which are released into the internal environment of the body. These Endocrine secretions are distinguished from exocrine secretions, which are released to the external environment. Thus, endocrine signaling occurs when endocrine cells release hormones that act on distant target cells in the body.
Endocrine signaling can be distinguished from two other types of signaling: neural signaling and paracrine signaling. The key difference between these types of signaling is the distance that the regulatory molecule travels to reach its target. Neurons are connected to their target cells via synapses. A neurotransmitter crossing a synaptic cleft will travel between 10 and 20 nanometers. However, paracrine will travel only a few millimeters before it is broken down, so it can only act on nearby cells. On the other hand, hormones travel via circulation to reach their targets, which are distant from the endocrine cells. Thus, hormones could be said to have systemic effects. The following figure depicts the differences between endocrine, neural and paracrine signaling.
Comparison of key characteristics of endocrine, neural and paracrine signaling.
In addition, the timing involved in endocrine signaling differs significantly from neural signaling. Neural signaling is brief and discrete, and usually starts and finishes in less than a second. Endocrine signaling takes longer because the hormone takes more time to reach its target, the response of target cells takes longer. To account for this significant timing difference, hormones are more stable and capable of signaling over longer times.

## Hormones

There are two main categories of hormones: either proteins or steroids. Only sex hormones and those derived from the adrenal cortex are to be considered steroids, everything else in the rest of the body are made from proteins or derivatives or proteins.
Hormone Mechanism Hormones that are transported via the blood throughout the whole body but only affect particular cells. The ones that to give a response to particular hormones have receptors that are very specific for that hormone. This is analogous to the lock-and-key mechanism. Essentially if the hormone, which is the key, fits into the lock or the specific receptor then the door will be unlocked. When hormones bind to the receptors there will essentially be an effect or action that occurs. When the hormones cannot bind to the receptor sites for various reasons, no reaction will occur. Essentially all the cells that have these receptor sites for the hormone compromise of the target area for the hormone. Sometimes the target tissues will be an centralized area such as in a gland or organ, but sometimes the target tissues disperses all over the body and this is how multiple areas may become affected at the same time. Hormones influence cells by altering the activity of cells. Steroid-type hormones will generally target the receptors which are located inside a cell. Protein-type hormones typically react with receptors that are located on the surface of cells, since this is so easily accessible the events that lead to completion occurs relatively accelerated rate. On the contrary, steroid hormones takes a bit longer because proteins have to be synthesized.
Hormone Control Hormones are extremely powerful in that minute concentrations will have very intense effects on processes of metabolism. With this great power, hormones must have strict parameters to follow so that equilibrium in the body can be maintained. A lot of hormones would be regulated by negative feedback. Glands initiating the hormone release from another gland will gradually be turned off- this is to avoid hormone imbalance and from production of way too much hormone. An example of this regulation occurs when hypothalamus, which secretes TRh and this prompts the pituitary to release TSH, which then prompts the thyroid gland to secrete T4 or also known as the thyroid hormone. After the body as sufficient amounts of thyroid hormone in the bloodstream, it is the T4 that goes back to the hypothalamus and pituitary to initiate the decrease of TRH and TSH secretion. Similar mechanisms of negative feedback also occurs in adrenal gland and the ovaries and testes.
Chemical Classes of Hormone 1. Polypeptides(proteins and peptides) 2. Amines 3. Steroids

## Endocrine Glands

Pituitary and Pineal Glands
Pituitary gland is a minuscule gland approximately 1 centimeter in its diameter. It is essentially encompassed by bone since it sits right in the sella turcica. This gland is actually connected right to the hypothalamus of the brain with what is known as the infundibulum. This gland is split up into two regions: one is the anterior lobe or also known as the adenohypophysis and the posterior lobe which is known as the neurohypophysis. The hormones that are released by the hypothalamus is what controls the adenohypophysis activity and posterior lobe is controlled by stimulation of nerves.
Hormones of Adenohypophysis Growth hormone, which is a protein, promotes the growth of muscles, bones, and even other organs and is done by creating new proteins. This hormone is what controls the height of an individual whether that person is tall or short. Having not know growth hormone as a infant, that person will be small and a dwarf. Too much hormone on the other hand will cause the person to be abnormally gigantic.
Thyrotropin which is also known as thyroid-stimulating hormone effects the glandular cells of the thyroid to give off the thyroid hormone. When too much of thyroid-stimulating hormone is secreted then the thyroid gland will become bigger and follow suite by secreting an ample amount of thyroid hormone as well.
Gonadotropic hormones will bind to the receptor sites which are located in the gonads, ovaries, or testes. Their role is to manage growth, development, and function of those three organs.
Prolactin hormone is what initiate the glandular tissue development in female breast at pregnancy and this also promotes the production of milk after the infant is already born.
Adrenocorticotropic hormone binds to the receptors in the cortex of the adrenal gland and this promotes the release of cortical hormones, but mostly cortisol.
Hormones of Neurohypophysis The hormone that is localized here is the antidiuretic hormone(ADH) and this prompts water reabsorption in the kidney tubules and so not as much water is loss in urine. The overall goal is to keep the water within the body. if one does not have enough of ADH, there will be a lot of water loss through urine.
Pineal gland is a small structure that looks like a cone and extends toward the back of the brain. This gland encompasses neurons, neuroglial cells, and pinealocytes. It is the pinealocytes that give off the hormone melatonin and inputs it right into the cerebrospinal fluid and then directly into the bloodstream. This hormone alters physiologic cycles and also reproductive development.
Thyroid and Parathyroid Glands
Thyroid Gland The thyroid gland is an organ centralized in the neck. It is made up of two lobes, where each is on one side of the trachea or right below the voice box. Isthmus is what connects these two lobes. Inside of the gland there are follicles, which is what produces the thyroxine and triiodothyronine hormones. Iodine is incorporated into these hormones.
Roughly 95% of the thyroid hormone that is active is thyroxine and the last percentages will be triiodothyronine. To be created, both of them require iodine. The secretion of thyroid hormone is controlled by negative feedback and this includes the hormone circulating around, hypothalamus, and adenohypophysis. Not having enough iodine, thyroid will not make enough hormone. When this occurs, the anterior pituitary is stimulated to release thyroid-stimulating hormone which affects the thyroid gland by increasing its size to attempt to produce more hormones and will obviously be ineffective. The hormones cannot be produced any more since one of the essential elements iodine is not present. This thyroid enlargement is what's called an iodine deficiency goiter.
Calcitonin is given off by the parafollicular cells in the thyroid gland. This has an opposite effect to the parathyroid gland by decreasing the calcium levels in the bloodstream. If the calcium in the blood is too high, calcitonin is given off all the way until the calcium ion levels decreases back to normal.
Parathyroid Glands On the back surface of the thyroid glands and in the connective tissues are four tiny pieces of epithelial tissue, which is known as the parathyroid gland. From this gland what is secreted is the parathyroid hormone or parathormone. Parathyroid hormone regulates how much calcium is in the blood. This hormone will be give off when there is low calcium levels in the blood and the hormone's role is to increase these levels.
Not having enough parathyroid hormone that is being secrete causes nerves to be more excitable. The effects of low calcium in the blood is that this causes random and unceasing nerve impulses and this promotes the contraction of muscles.
Adrenal Gland
The adrenal gland is what sits on top of both of the kidneys. Each glad is divided into two parts: outer cortex and then the inner medulla. Both of these parts of the adrenal gland are synonymous to there being two parts of the pituitary, since it is produced from dissimilar embryonic tissues and will secrete different hormones. Actually only the adrenal cortex is necessary to the body but if body can do without the medulla and have no serious adverse effects.
Both parts of the adrenal gland are controlled by the hypothalamus. Negative feedback is what regulates the adrenal cortex and includes the hypothalamus and adrenocorticotropic hormone. The hypothalamus will give nerve impulses to help control the medulla portion of the adrenal gland.
Hormones of Adrenal Cortex Even within the adrenal cortex, it is separated into three distinctive regions as well, and each region produces its own characteristic type of hormone. In chemical form, the cortical hormones made up of steroids. Mineralcorticoids is what's secreted by far outside of the adrenal cortex. A primary mineralocorticoid would be aldosterone, which influences or increases the conservation of sodium and water that is in the body. The middle region secretes glucocorticoids. Its primary type is cortisol which acts to increase the glucose concentration in the blood. The third or last group, which is in the far inside region is called the gonadocorticoids or also known as sex hormones. Androgens, which is male hormones and estrogens, which is female hormones, are actually secreted by both females and males in minute amounts. The reason why it seems as if they do not have an effect is that hormones derived from the testes and ovaries will cover up their effects.
Hormones of Adrenal Medulla
Neural tissues create the adrenal medulla and it is here that two hormones are secreted- epinephrine and norepinephrine. During a sympathetic response, usually during times that are stressful both of these hormones will be secreted. Secreting too much of this hormone may cause extremely long or perennial sympathetic responses. Having too little of this hormone does not have any substantial effects.
Pancreas
The pancreases is a long organ that lies crosswise the back of the abdominal wall, to the back of the stomach, and spans from the duodenum to the spleen. The pancreas has two portions an exocrine portion that gives off digestive enzymes for food through to the duodenum and an endocrine portion, which is made up of pancreatic islets and secretes both insulin and glucagon.
There are two types of cells in the islets and they are alpha cells and beta cells. Alpha cells will secrete the glucagon hormone when there is low concentration of glucose in the bloodstream. Beta cells will react in the reverse, when there is high glucose concentration in the bloodstream the insulin hormone will be secreted.
Gonads
Gonads are the principle reproductive organs, where the testes are for men and ovaries in the female. Not only do they secrete sperm and eggs, but since they are both viewed as endocrine glands they secrete hormones as well.
Testes Androgens when are collectively as sex hormones for male are known as androgens. The primary androgen is the testosterone, which is released from the testes. The adrenal cortex also produces a very minute amount of this hormone. Testosterone creation starts during fetal development and stops shortly after birth. Production is nearly none during fetal development and commences after puberty. This hormone has a number of responsibilities including development of male reproductive structures, increases growth of muscles and skeletons, widening of the larynx and changing of voices, distribution of hair on the body, and lastly an sexual drive for males that is increased. This testosterone production is managed by negative feedback which includes releasing hormones from both the hypothalamus and gonadotropins, which is from the anterior pituitary.
Ovaries There are two types of groups of hormones made in the ovaries- both estrogen and progesterone. These hormones are of the steroid type and aid in the development of the female reproductive organs. When puberty commences, estrogens initiate breast development, allocation of fat to the hips, legs, and the breasts, and maturing of the reproductive organs such as the vagina and the uterus. The hormone progesterone brings about the thickening of the uterine and this is done to prepare for pregnancy. Both the progesterone and estrogen induce the changes in the uterus during the menstrual cycle.
Endocrine in Organs Aside from the big endocrine glands, there are other organs that utilize hormones as part of their way to get things done. Organs that use hormones include thymus, stomach, small intestines, and heart.
Development of the body's immune system is greatly helped by thymosin from the thymus gland. In the stomach's lining known as the gastric mucosa creates a hormone known as gastrin, which is activated by food in the stomach. Gastrin promotes the production of hydrochloric acid and along with the pepsin enzyme- all of which aids in digestion. WIthin the mucosa of the small intestine has two hormones secretin and cholecystokinin. Secretin prompts the pancreas to produce bicarbonate so that the stomach acid can be neutralized. Cholecystokinin prompts the gallbladder to compress it and bile is released. The heart is called an endocrine organ. Certain cells in the atria produces atrial natriuretic hormone.

## Common Endocrine Diseases and Disorders

Diseases and disorders of the endocrine system can be grouped in various ways. Typically endocrinologists will take a target one or two endocrine diseases to focus on.
Diabetes
People that have abnormally high levels of sugar in their bloodstream. There have been research done that shows that manager the amount of sugar in the blood aid in preventing adverse effects stemmed from diabetes. Some of the problems include problems with the nerves, kidneys, and eyes, and gradually may lead to blindness or even amputation. Diabetes patients are treated with a new diet and drugs including insulin. Patients need to help keep their blood sugar low and be monitored so that other health problems may be avoided. Type 1 diabetes - insulin-dependent diabetes, is an autoimmune disorder in which the immune system destroys the beta cells of the pancreas. Therefore, a person cannot produce insulin. Type 2 diabetes - non-sinulin-dependent diabetes, is caused by a failure of target cells to respond normally to insulin.
Thyroid
People with adverse thyroid circumstances a lot of the time have lack of energy. Not only this but also conflicts in strength of muscles, controlling weight, very emotional, and also withstanding the hot or cold weather. Typically their problem is that the amount of thyroid hormone is either over-abundant or immensely lacking, which is resultant from either too active or not to active thyroid. The solution for this would be to reach back to a hormone equilibrium by either restoring or obstructing the thyroid hormone. Other potential problems with thyroid include thyroid cancer and also to have an overtly big thyroid gland.
Bone
Problems with bones include rickets- the softening of bones or osteoporosis- making fragile bones, can both be treated with the endocrine system. There are particular hormones that are designed to guard bone tissue. Having anomalies in hormone levels, calcium may be depleted from bones and then become less strong. Losing function of the testicle in men or menopause in women puts the population at higher risk for bones to break. Other problems that affect bones include an over-abundant parathyroid hormone and using steroids such as prednisone for a while.
Reproduction or Infertility There is a staggering statistic that approximately 10% of couples in America are infertile. Endocrine hormone imbalances may lead in infertility and knowing the source the reproductive conflicts may be addressed. Reproductive endocrinology may be used to work with patients who have irregular periods, premenstrual syndrome, and impotence.
Obesity and Overweight
People that are overtly obese have their source of problems as metabolic or hormonal. Problem in pathways of thyroid, adrenal, ovarian, or pituitary can lead to obesity. More specific reasons associated with obesity include resistance to insulin and also problems in genes.
Pituitary Gland Pituitary gland manages all of the other glands and so it is sometimes called the master gland. The pituitary do make a lot of important hormones. Too much or too little production of these hormones can lead to imbalance and then cause infertility, disorders in growing, and possibly too much cortisol. These conditions are helped through drugs and sometimes might require surgery.
Growth
Not having enough growth hormone result in children that have disorders in growing and remain short. Growth hormone problems that occurs in adults, make them often feel tired and have emotional distress. Growth hormone replacement therapy can help to manage this imbalance.
Hypertension
High blood pressure could cause eventual problems with the heart. About 1/10 of people will have hypertension as a result of an over-abundance of aldosterone- which is produced from adrenal glands. About 1/2 of the cases the initiate these types of growth can be taken out through surgery. Other smaller factors that can lead to hypertension include a metabolic syndrome or pheochromocytoma and this causes hormonal imbalance which then induces hypertension.
Lipid Disorders Lipid disorders cause problems with up-keeping the right levels of body fats. Hyperlipidemia, an example, is having super saturate levels of overall cholesterol, low-density lipoprotein, triglycerides in the bloodstream. Having copious amounts of these fats are very associated with heart disease, strokes, and troubles with circulation in legs. Potential causes to disorders caused by lipids could be to less thyroid hormone, steroid drug use, or problems in metabolic or gene regulation. Solutions to help fix this problem may include certain diets, exercise, and drugs.

## Endocrine Disruptors

Endocrine Disruptors are various types of chemicals that can be both natural or made by humans that disrupts the endocrine system and has detrimental effect on humans, fish, and other organisms. They interfere with the creation or hormone activity of the endocrine system and is damaging to health.
How Endocrine Disruptors work Endocrine disruptors have three main ways in which they work. The first one is to simulate the hormones, which occur naturally in the body such as androgens or the male sex hormone and has the ability to overstimulate. Another way is to bind to receptors in that cell and then block the real hormone from binding. Without the proper signals, the body cannot respond in a proper manner. Examples could include anti-androgens that block the real hormones from binding. Lastly, disruptors affects the way hormones are produced or receptors and their control mechanisms. An example is blocking the metabolism of hormones in the liver.
Endocrine Disruptors examples
There are numerous substances that are probable of causing endocrine disruption. Chemicals that are for certain endocrine disruptors include DES, PCBs, DDT, and other types of pesticides. Examples of probable ones are pesticides and plasticizers like Bisphenol A, which is from animal studies.
Exposure to Endocrine Disruptors
Exposure is very widespread. It can be anything from food and beverages to cosmetics and drugs. Exposure usually happens through either air, diet, or skin.

## References

"Endo 101: Control fo the Endocrine System by Negative Feedback." <http://www.hormone.org/Endo101/page3.cfm>. 2 Dec. 2009.
"Endocrine Disruptors." National Institute of Environmental Health Sciences. <http://www.niehs.nih.gov/health/topics/agents/endocrine/docs/endocrine.pdf>. June 2006. 1 Dec. 2009.
"Introduction to the Endocrine System." National Cancer Institute. <http://training.seer.cancer.gov/anatomy/endocrine/glands/adrenal.html>. 2 Dec. 2009.
"What is an Endocrinologist?" The Hormone Foundation. <http://www.hormone.org/public/endocrinologist.cfm>. Jan 2008. 2 Dec. 2009.