domingo, 2 de julio de 2017

Endocrine System

The endocrine system is, along with the nervous system, the main controller of bodily functions. Both systems are coordinated to carry out their functions and they control each other: the nervous system controls the production and secretion of hormones and some hormones can control the nervous system.
Both systems have, however, some relevant differences. The nervous system carries out its functions very quickly, in milliseconds. And it controls punctual or not very lasting actions. The endocrine system, on the other hand, carries out its functions more slowly, in seconds or even minutes. And it controls lasting actions, that can take minutes, such as the vasodilation promoted by some hormones, hours, such as the digestive process or even years, such as growth.
The endocrine system is the main regulator of the homeostasis and metabolism (both anabolism and catabolism). Its functionality is based on the secretion of chemical substances called hormones. They are produced and released by endocrine glands.

Hormones can be defined as organic molecules responsible for transmitting signals between different parts of the body. Together with the neurotransmitters (that communicate neurones linked by synapses), they are the main chemical messengers.
The hormones are usually transported by the blood. They can carry out their actions at extremely low concentration. Although the blood moves the hormones throughout the whole body, they only act upon some organs or cells. These cells or organs that carry out some specific action when they detect a hormone are called target cells or organs. Only one hormone is perceived, and can only act in cells with specific receptors to detect this hormone.
There are four types of hormones, according to their chemical composition:
  • Steroid hormones: they derive from cholesterol. For example, the sexual hormones.
  • Amino acid derived hormones: they are modified amino acids working as chemical messengers. Adrenaline, for instance.
  • Peptides and proteins: chains made up of amino acids. Insulin, for instance.
  • Eicosanoids: these hormones derive from lipids (nearly all of them with 20 carbon atoms). The most relevant examples are prostaglandins.
Hormonal function
When a hormone reaches the target cell, it should bind with its receptor. Then, two different processes can occur:
  • The receptor can be located in the plasmatic membrane of the cell, so the hormone does not enters the cell, but it binds to the receptor. The receptor send a signal to the interior of the cell. This signal is transmitted from the membrane to the interior by chemical substances called secondary messengers. These secondary messengers are detected by internal proteins that can carry out different actions, such as activating genes to produce new proteins. There are many different secondary messengers but the most typical ones are the cyclic AMP and the substances derived from inositol. This process is typical for amino acid derived hormones and peptides (because they can't cross the membrane).
  • The receptor can be located in the interior of the cell. Then the hormone enters the cell, directly crossing the membrane or using a transporter. The hormone binds to the internal receptor and they move to the nucleus, where they carry out their actions, merely changing the expression of genes. Sometimes they can also promote the synthesis of secondary messengers that transmit information to different parts of the cell. These processes are typical for steroid hormones and eicosanoids (because they can easily cross the membrane without any kind of transporter).
Endocrine glands and hormones
The endocrinology studies the different endocrine glands. It also analyses the most relevant hormones produced and released by these glands and their main functions.
Hypothalamus – Pituitary Gland
The Hypothalamus - Pituitary - Adrenal axis is the main path that control the endocrine system. Many hormones are directly produced by these glands, or are controlled by hormones produced by this axis. 
The hypothalamus is a part of the brain, in the cerebrum, located in its central area. It is directly connected to the pituitary by a neural connection. The hypothalamus is a part of the cerebrum that receives impulses from the brain, so this connection with the pituitary is the main relationship between the nervous and the endocrine systems. The hypothalamus controls the pituitary sending neural impulses or hypothalamic hormones.
The pituitary gland is a tiny organ located under the brain, found in a depression of the sphenoid bone called the Turkish seat. It produces several hormones although many of them do not have direct action on target organs, but on other endocrine glands, promoting or inhibiting the production of other hormones.
The pituitary gland has three parts, called anterior, intermediate and posterior lobe. The anterior lobe is made up of nervous tissue and the posterior lobe is made up of glandular epithelial tissue. The anterior lobe does not produce hormones, but it releases hormones that have been produced by the hypothalamus. These hormones descend from the hypothalamus to the anterior lobe through the connection between them.
There are two relevant hormones released by the anterior lobe of the pituitary gland:
  • Oxytocin (Ox): it is responsible for the contraction of the womb during delivery. The contractions are triggered by an abrupt increase in the oxytocin levels. It also stimulates the secretion of milk. In some mammals it is also related to some sexual behaviours, such as monogamy.
  • Antidiuretic Hormone (ADH): it is also called vasopressin. It regulates the production of urine. When the osmo-receptors in the hypothalamus detect high osmotic pressure, derived from descend of body fluids, the neurones produces ADH, that is secreted by the pituitary gland. This hormone induces the reabsorption of water by the kidneys. It also reduces the secretion of urine. Besides, it increases the arterial pressure causing vasoconstriction and prevents losing water by perspiration.
The posterior part of the pituitary gland secretes several hormones. The secretion of these hormones is promoted or inhibited by hormones secreted by the hypothalamus. In other words, the hypothalamus secretes hormones that stimulate or inhibit the production of other hormones by the posterior lobe of the pituitary gland.
These are the most relevant hormones released by the pituitary gland:
  • Growth Hormone (GH): it is also called somatotropin. Its secretion is regulated by to hypothalamic hormones, the Somatostatin (GHIH) that inhibits the production of GH, and the Growth Hormone-Releasing Hormone (GHRH) that stimulates its production. The GH stimulates the synthesis of proteins, the consumption of fats and the production, by the liver, of other hormones that directly control the growth process. These hormones produced by the liver are called Somatomedin and Insulin Growth Factors (IGFs).
  • Thyroid-stimulating Hormone (TSH): it is also called thyrotropin. It stimulates the production and secretion of T3 y T4 by the thyroid gland. The pituitary gland releases TSH when it detects Thyrotropin (TRH), that is produced by the hypothalamus. The thyroid gland controls many body processes, so the secretion of these hormones depends on the general body conditions.
  • Follicle-stimulating Hormone (FSH) and Luteinizing Hormone (LH): these are the most relevant  gonadotropins produced by the pituitary gland. These hormones control the sexual cycles. In females, the FSH stimulates the development of ovarian follicles and the secretion of oestrogens, whereas the LH promotes the releasing of the oocyte and the production of Progesterone by the Corpus Luteum. In males the FSH stimulates the production of spermatozoa, whereas the LH promotes the production of Testosterone (the main sexual hormone in males). Both hormones are produced by the pituitary gland when it detects the Gonadotropin-Releasing Hormone (GnRH) produced by the hypothalamus.
  • Prolactin (Prl): this hormone promotes the production of milk by the mammary glands. Its production is usually inhibited by the Prolactin-Inhibiting Hormone (PIH), that is synthesised by the hypothalamus. During pregnancy, the hypothalamus stops producing PIH and starts releasing Prolactin-Releasing Hormone (PRH), that stimulates the synthesis of Prl by the pituitary gland. Prolactin stimulates the production of milk, but it is also inhibits the sexual hormones. Due to this, the menstrual cycle stops for some months after birth and the hormone works as a natural contraceptive system. This hormone does not have any relevant known function in males, although some disorders in its synthesis can cause impotence.
  • Melanocyte-Stimulating Hormone (MSH): this hormone is produced by the intermediate lobe of the gland and it promotes the synthesis of melanin by the melanocytes, stimulating the skin pigmentation. It does not have any relevant role in human beings, but it is very important in mimetic animals. Its production is controlled by two hypothalamic hormones, the Melanocyte-Stimulating Releasing Hormone (MRH) that promotes its secretion and the Melanocyte-Stimulating Inhibiting Hormone (MIH) that inhibits its secretion.
  • Adrenocorticotropin (ACTH): this hormone controls the production and secretion of several adrenal hormones called glucocorticoids. The secretion of this hormone is controlled by the Corticotropin-Releasing Hormone (CRH), produced by the hypothalamus. It can also be released after some physical stimuli, such as infections, traumas or hypoglycaemia.
Thyroid Gland
This gland is located under the larynx and it is made by two lateral lobes called left and right lobes, in both sides of the windpipe, joined by the isthmus and the pyramidal lobe.

When the gland detects TSH, released by the pituitary gland, it produces and released triiodothyronine (T3) and tetraiodothyronine, also called thyroxine (T4). These are the main thyroid hormones, although this gland also produce Calcitonin (CT).
The thyroid hormones are essential to control the metabolism. They control the cellular metabolism, the basal metabolic rate and the oxygen consumption. They are also involved in the growth and development of the body. They increase the basal metabolic rate or, in other words, the minimal energy required to support the body functions. They also increase the consumption of oxygen. As a result, they cause higher body temperature. They promote the consumption of fats, lipids and glucose. They accelerate the body growth, above all in the nervous system. 
The Calcitonin (CT) is, with the Parathormone (PTH) released by the parathyroid gland, the hormone responsible for controlling the calcium and phosphorus levels in the blood. It inhibits the destruction of bone, reducing the levels of calcium in the blood (when the bone is destroyed, the calcium is transported to the blood). And, at the same time, it controls the concentration of PO43- y HPO42- because these ions are usually associated to the calcium (indeed, the bones are made of hydroxyapatite, a salt of calcium and phosphorus). Calcitonin, however, is not the most relevant hormone to control these ions, and the main regulator is the parathormone.
Parathyroid Glands
These are four small glands attached to the surface of the thyroid gland. There are two parathyroid glands in each lobe, one in the upper part and another one in the lower part. 

They produce and release the Parathyroid Hormone (PTH), that is the main hormone to control the calcium and phosphorus metabolism. It increases the number and activity of the osteoclasts, promoting the destruction of bone tissue and increasing the levels of calcium and phosphates in the blood. In the kidneys, it promotes the reabsorption of calcium, although, at the same time, it promotes the release of phosphates in the urine. As a result, the hormone increases the levels of calcium, but reduces the levels of phosphates.
The production of PTH is controlled by the levels of calcium in the blood. When this level descends, the PTH is produced and released.
Adrenal Glands
There are two adrenal glands, located above the kidneys. They have two different parts, the external part called adrenal cortex, and the internal part called adrenal medulla. The medulla is smaller than the cortex. 

The adrenal cortex has three parts that produce different hormones.
The outer part of the adrenal cortex is called zona glomerulosa and it is responsible for producing mineralocorticoids. The intermediate part is called zona fasciculata and it is responsible for producing glucocorticoids. Finally, the inner part is called zona reticularis and it is responsible for producing gonadocorticoids.
These are the most relevant cortical hormones:
  • Mineralocorticoids: they control the homeostasis, above all the levels of sodium and potassium ions. The most relevant mineralocorticoid is the Aldosterone (Ald), that acts in the kidney, promoting the reabsorption of sodium, chlorine and bicarbonate, increasing the elimination of potassium and protons (preventing our body from acidosis). It is controlled by the renin-angiotensin system, that are activated by low concentration of sodium or low volume of blood. The renin is an enzyme produced by the kidney that modifies a protein produced by the liver, called angiotensinogen. The angiotensinogen is inactive, but it is transformed into the active hormone, called angiotensin by the renin. The angiotensin promotes the secretion of Aldosterone.
  • Glucocorticoids: the most relevant ones are the cortisol, the cortisone and the corticosterone. They increase the catabolism of proteins and the production of glycogen to build up sugars. They also stimulate the consumption of lipids. They prepare our body from stress. They are also anti-inflammatory substances and reduce the production of histamine, working as anti-allergic. These hormones are produced when the adrenal cortex detects ACTH secreted by the pituitary gland.
  • Gonadocorticoids: they are sexual hormones produced by the zona reticulata. They are not very important, but they can cause some health problems, such us hirsutism, when they are over-produced.
The adrenal medulla is directly innervated by the autonomous nervous system, that controls the production and secretion of hormones. As a result, its secretion is extremely fast.
The main hormones of the adrenal medulla are the noradrenalin and the adrenalin (also called epinephrine). They have the same functions as the sympathetic nervous system and are responsible for getting the body ready for defensive and offensive reactions (called fight-or-flight reactions): fighting, running away, attacking, etc. They increase the arterial pressure, and the heart beat and respiratory rate, they improve the muscular contraction, stimulate the cellular metabolism and raise the glucose levels in blood. They also cause pupil and arterial dilation.
Endocrine Pancreas
This is the part of the pancreas that produce hormones. Indeed, the pancreas has groups of cells that form structures called islets of Langerhans where these hormones are secreted to the blood. These hormones are essential to control the digestion and the metabolism of sugars. The most important pancreatic hormones are:
  • Glucagon: it is produced when the glucose level in blood descends and it is responsible for promoting the rising of glucose in blood. In the liver, it accelerates the transformation of glycogen into glucose that is released to the blood and it also stimulates the production of glucose from its precursors and the catabolism of fats.
  • Insulin: it is produced when the glucose level in blood ascends and it is responsible for reducing it. Its actions are opposite to glucagon. It stimulates the transformation of glucose into glucagon in the liver. It also promotes the production of proteins and fats from its precursors.
The pancreas also produces other two hormones: the pancreatic somatostatin (GHIH), that is responsible for stopping the secretion of insulin and glucagon, and the Pancreatic Peptide (PP), that controls the production of digestive enzymes.
Pineal Gland
The pineal gland is located in the roof of the third cerebral ventricle. The most relevant hormone produced by this gland is the Melatonin (Mel). This hormone has a rhythmical secretion, in twenty-four-hours-cycles, also known as circadian cycles. Its secretion is higher during night and lower during day, merely because light inhibits its secretion. 

It controls the physiological changes between night and day. For instance, it inhibits the central nervous system to ease sleep. It also inhibits the sexual hormones. Due to this, the secretion of melatonin falls during adolescence in order to allow the body to grow up, ascending after maturation. It also descends during senescence. The hormone protects the body from ageing, so when its levels descends during senescence the effects of the ageing become more important.
The thymus produce hormones that promotes the proliferation and maturation of defensive cells, above all lymphocytes.
The best known thymic hormones are the Thymosin, the Thymic Humoral Factor and the Thymopoietin.
Sexual Organs
The sexual organs are different in males and females and their secretions are also different.
The most important secretive part in the female reproductive system is the ovary. When this organ is stimulated by the gonadotropins (released by the pituitary gland) it produces and secretes two different kind of hormones:
  • Oestrogens: there are several types of oestrogens. The most relevant one is the stradiol, that is responsible for the development of the female sexual organs and the secondary sexual characteristics in females, such as the distribution of hair.
  • Progestogens: they are responsible for controlling the menstrual cycle, above all the development of the uterus wall, that must be in optimum state in order accommodate the fertilised ovule. The most relevant progestogen is the progesterone.
As far as the male sexual reproductive system is concerned, the main secretive organs are the testicles. The male hormones are called androgens and the most relevant one is the testosterone.  It promotes the production and maturity of spermatozoa, the development of the male sexual organs and the secondary sexual characteristics in males, such as the body hair or the muscular growth.
Other organs that produce hormones

Many organs and tissues can produce hormones in some circumstances. The kidney, for instance, produce and release Erythropoietin when it detects low amount of erythrocytes in blood. The heart produce a vasodilator called Atrial Natriuretic Peptide when the atrial cells detect over-expansion. 

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