Introduction to Endocrinology History of endocrinology, Brief introduction of endocrine glands, Classification, Characteristic and Transport of Hormones, Neurosecretions and Neurohormones
Introduction
Each endocrine gland consists of a group of specialized cells that have a common origin in the developing embryo. Some endocrine glands, such as the thyroid gland and the islets of Langerhans in the pancreas, are derived from cells that arise in the embryonic digestive system. Other endocrine glands, such as the parathyroid glands and the adrenal medulla, are derived from cells that arise in the embryonic nervous system. Certain glands, including the ovary, testis, and adrenal cortex, arise from a region of the embryo known as the urogenital ridge. There are also several glands that are derived from cells that originate in multiple regions of the embryo. For example, the pituitary gland is composed of cells from the nervous system and the digestive tract.
Most hormones are one of two types: protein hormones (including peptides and modified amino acids) or steroid hormones. The majority of hormones are protein hormones. They are highly soluble in water and can be transported readily through the blood.
Hormones act on their target tissues by binding to and activating specific molecules called receptors. Receptors are found on the surface of target cells in the case of protein and peptide hormones, or they are found within the cytoplasm or nuclei of target cells in the case of steroid hormones and thyroid hormones.
Endocrine glands :
History of Endocrine Gland
The history of endocrinology can be broadly classified into three phases: the 1st phase of description of endocrines, the 2nd phase of analytical endocrinology, and the 3rd phase of synthetic endocrinology.
In 1905 Starling proposed the name "hormone" for this class of internal secretions. By then endocrinology had been launched as a new branch of science.
Endocrinology was recognized as a new branch of biological science mainly as a result of events which took place between about 1890 and 1905, but ideas and discoveries dating from antiquity contributed to it also. Experiments supporting the concept of internal secretions by the testicles were described by Aristotle (4th c. B.C.) and by Hunter (18th c.) and Berthold (19th c.).
In 17th and 18th centuries, the practice of castration was probably the first evident history of endocrinology. People used to undergo castration (termination of testicular activity) before puberty to maintain pure and forceful voice and enhance breathing control.
The practice came to an end in the 20th century when people understood that there were many adverse side-effects, such as loss of temporal hair recession, longer than normal length of arms and legs, etc.
In 1849, Berthold, a German physiologist, conducted some experiments on capons (castrated rooster) to prove that transplanting testes from intact bird into capons’ abdomens can recover normal male characteristics. However, his discovery remained unnoticed.
In 1889, Brown-Séquard, a French physician, injected himself with a preparation made up of blood from testicular veins, semen, and extracts of the dog, guinea pig, or rabbit testicles and reported significant improvement in his strength, stamina, and concentration. He was probably the first person who came with an idea of endocrine replacement therapy.
The idea of the replacement therapy was next nurtured by a famous surgeon, Victor Horsley, who initially noticed that dissecting the thyroid gland from monkey led to development of myxedema symptoms.
Later, he proposed transplantation of sheep’s thyroid into human patients to improve clinical outcomes. His idea was cultivated by another physician, George Murray, who made an extract of sheep’s thyroid (pink thyroid juice) and injected it into a woman patient and found an astonishing improvement in her condition.
In 1855 Bernard described glucose as an internal secretion of the liver and Addison reported the effects of adrenal disease in man. Adrenalectomy was fatal in animals.
Goitre was known in antiquity and cretinism had been described by Paracelsus. Myxoedema was reported by Gull in 1873. In 1888 cretinism, myxoedema were attributed to thyroid insufficiency.
In the 1890s Gley found that tetany after thyroidectomy was due to removal of the parathyroids. In 1884 Rehn proposed that toxic goitre was due to thyroid excess.
In 1889 Brown-Séquard claimed that injections of testicular extract rejuvenated the elderly, and in 1893 he introduced organotherapy.
In 1891 Murray treated myxoedema successfully with thyroid extract.
In 1893 Oliver and Schäfer found that an adrenal extract raised the blood pressure, and soon adrenaline was extracted from the adrenal medulla.
Adrenocortical deficiency was proposed as the cause of Addison's disease.
Diabetes mellitus, described in the first century, was usually fatal. Thirst and polyuria followed experimental pancreatectomy, and pancreatic lesions were found in some human diabetics.
In the 19th century workers in France and Germany found that diabetes resulted from absence of an internal secretion by the islets of Langerhans and, in 1893, Laguesse described the function of the islets as "endocrine".
In 1895 Beatson treated advanced breast cancer successfully by ophorectomy.
In 1895 Schafer commended study of the internal secretions to physiologists.
In 1902 Bayliss and Starling discovered secretin, a chemical messenger secreted by the intestinal mucosa.
Discovery of insulin
In the period of 1900 – 1930, many hormones were identified, and a wide range of research on hormone biochemistry, reproductive cycle, and endocrine-related surgeries were performed
In 1921, Frederick Banting and Charles Best conducted an experiment on diabetic dogs and cured the condition with pancreatic islet cell extracts of healthy dogs. This marked the discovery of insulin. Moreover, Frederick Banting isolated insulin after inactivating the exocrine part of the pancreas by ligation.
In 1921, insulin was injected for the 1st time into Leonard Thompson who was suffering with type 1 diabetes. This treatment completely reversed his condition, which used to be life-threatening before the discovery of insulin.
Discovery of sex hormones
In the late 19th and early 20th centuries, Eugen Steinach discovered sex hormones through his experiments on rats. He removed the testicles from rats and implanted them in rat’s abdomen, and he found that normal male characteristics of the rats were terminated. Later, he revealed that interstitial cells of the testes produce male sex hormones.
Eugen Steinach also developed a procedure to increase testosterone level in the body. His experiments revealed that both testosterone level and sexual drive can be increased in men by sealing or tying off the ducts (vas deferens) that carry sperm from the testes to the penis. This procedure is called vasectomy in the modern era of endocrinology.
All these revolutionary findings together paved the way to modern endocrinology. The discovery of endocrine system has a very long and rich history, starting from the dark ages when Victors of battle ate the organs (brain, heart, gonads) of enemies thinking that they contained important powers. The journey still continues with exciting and innovative discoveries, such as discovery of leptin and its association with obesity.
Classification of Hormones
Animals have two systems of internal communication and regulation: •
1. The nervous system
2. The endocrine system
The Nervous system conveys high-speed electrical signals along specialized units called Neurons.
The Endocrine system, made up of endocrine glands, secretes hormones that coordinate slower but longer-acting responses to stimuli.
A Hormone is a chemical signal that is secreted into the circulatory system and communicates regulatory messages within the body.
Hormones may reach all parts of the body, but only certain types of cells, target cells, are equipped to respond.
Signaling by any of these molecules involves three key events –
Reception -Signal transduction –Response.
Steroids Non steroid -Protein and polypeptides -Tyrosine-derived -Eicosanoids –Vitamins
Steroid Hormones: -Lipid soluble -Diffuse through cell membranes -Endocrine organs -Adrenal cortex -Ovaries -Testes –Placenta
Non-steroid Hormones: -Not lipid soluble -Received by receptors external to the cell membrane Endocrine organs -Thyroid gland -Parathyroid gland -Adrenal medulla -Pituitary gland -Pancreas
Group 1
Hormones- binds to Intracellular receptors, to form receptor complexes, mediate biochemical functions. Mostly lipophilic in nature.
Group 2
Hormones- binds to cell surface receptors and stimulate the release of secondary messengers which in turn perform biochemical functions.Thus, hormones itself is the first messengers.
Group 2 hormones are subdivided into three categories based on chemical nature of the second messenger 1. cAMP
2. phosphatidylinositol /calcium ,
3. Some cases second messenger is unknown.
Types of Hormones
Signaling Near and Far
Chemical Structures
Water vs Fat Solulable
Hormones are molecules that carry instructions from more than a dozen endocrine glands and tissues to cells all over the body. Humans have about 50 different known hormones, which vary in their structure, action and response. They control a variety of biological processes including muscle growth, heart rate, menstrual cycles and hunger.
Hormones travel throughout the body, either in the blood stream or in the fluid around cells, looking for target cells. Once hormones find a target cell, they bind with specific protein receptors inside or on the surface of the cell and specifically change the cell's activities. The protein receptor reads the hormone's message and carries out the instructions by either influencing gene expression or altering cellular protein activity. These actions produce a variety of rapid responses and long-term effects.
Hormones vary in their range of targets. Some types of hormones can bind with compatible receptors found in many different cells all over the body. Other hormones are more specific, targeting only one or a few tissues. For example, estrogens, the female sex hormones, can regulate function by binding to special estrogen receptor sites in uterine, breast and bone cells.
In addition, the same cell can act as a target cell for many different regulatory molecules. For instance, the same uterine, breast and bone cells that accept estrogens, also contain progesterone, androgen, glucocorticoid, vitamin D and vitamin A receptors.
Signaling Near and Far
Hormones are classified (separated into groups) according to how they travel in the body and their chemical structure.
Paracrine, autocrine and synaptic are three types of local hormone signaling. In paracrine signaling, hormones are released into the fluid between cells (the interstitial fluid) and diffuse to nearby target cells. Hormones that influence secretions or other processes on the same cells that released them are said to be autocrine signalers. The more specialized synaptic signaling occurs between neurons (the nerve cells that make up the nervous system) and between neurons and muscle cells, allowing nerve cells to talk to each other and to muscles.
Synapse
Hormones released into the bloodstream from endocrine gland cells and special cells in the hypothalamus (neurosecretory cells) travel throughout the body looking for target cells. These hormones are similar to a television signal in that they are broadcast everywhere but can only be picked up and read by a cell with the right hormone receptor or antenna.
Chemical Structures
Hormones are also grouped according to chemical structure. Structures dictate if the hormone prefers to be surrounded by water or fat (water or fat soluble), which determines:
if the hormone travels in the blood alone or attached to a protein
if the hormone will bind to receptor sites outside or inside of the target cell (fat soluble can bind both whereas water soluble hormones usually bind on the outside) and how the hormone is broken down (metabolized).
Three general structures are known.
Steroid hormones are fat-soluble molecules made from cholesterol. Among these are the three major sex hormones groups: estrogens, androgens and progesterones. Males and females make all three, just in different amounts. Steroids pass into a cell's nucleus, bind to specific receptors and genes and trigger the cell to make proteins.
Amino acid derivatives, such as epinephrine, are water-soluble molecules derived from amino acids (the building blocks of protein). These hormones are stored in endocrine cells until needed. They act by binding to protein receptors on the outside surface of the cell. The binding alerts a second messenger molecule inside the cell that activates enzymes and other cellular proteins or influences gene expression.
Insulin, growth hormone, prolactin and other water-soluble polypeptide hormones consist of long chains of amino acids, from several to 200 amino acids long. They are stored in endocrine cells until needed to regulate such processes as metabolism, lactation, growth and reproduction.
Water vs. Fat Soluble
Most water-soluble hormones, like the amino acid derivatives and peptides, can travel freely in the blood because they "like" water. However, they are repelled by lipid or fatty structures such as the membranes that surround the cell and nucleus. Because of this, these hormones generally bind to receptor sites on the outside of the cell and signal from there.
Fat-soluble hormones, like the sex hormone steroids estrogens and androgens, are fat soluble and water repellent. Steroids generally travel to their target cells attached to a special carrier protein that "likes" water (such as, sex steroid hormone binding globulin and serum albumin). The hormones detach before passing into the cell where they bind to receptors.
Neurosecretion (Regulated Exocytosis in Neuroendocrine Cells) and Neurohormone
specially modified nerve cells within the nervous system secrete important hormones into the blood. These special nerve cells are called neurosecretory cells, and their secretions are termed neurohormones.
Neurosecretion is generally understood to mean release of peptides or amines from specialized neurons into the circulation. In mammals, the classical neurosecretory systems secrete oxytocin or vasopressin from axon terminals in the posterior pituitary and also peptides and amines controlling the anterior pituitary.
The peptides and amines are packaged in dense core vesicles which are released by exocytosis. The mechanism of exocytosis is similar to that in other cells and requires an increase in intracellular calcium. Neurosecretory neurons are known to exocytose dense core vesicles also from their dendrites.
Neurohormone, any of a group of substances produced by specialized cells (neurosecretory cells) structurally typical of the nervous, rather than of the endocrine, system. The neurohormones pass along nerve-cell extensions (axons) and are released into the bloodstream at special regions called neurohemal organs.
Neurohormones thus constitute a linkage between sensory stimuli (events or conditions perceived by the nervous system) and chemical responses (endocrine secretions that act on other tissues of the endocrine system or on tissues of other systems, such as those involved with excretion or reproduction)
A second group of neurohormones, called releasing hormones also originates in the hypothalamus. The members of this group, however, are transmitted within the neural cells to a second locus in the brain, from which they pass in the bloodstream to the adenohypophysis, which also is a part of the pituitary gland. There they either stimulate or inhibit the release of the various adenohypophysial hormones.
Functions of Endocrine system
Endocrine gland secretion is not a haphazard process; it is subject to precise, intricate control so that its effects may be integrated with those of the nervous system and the immune system. The simplest level of control over endocrine gland secretion resides at the endocrine gland itself. The signal for an endocrine gland to secrete more or less of its hormone is related to the concentration of some substance, either a hormone that influences the function of the gland (a tropic hormone), a biochemical product (e.g., glucose), or a biologically important element (e.g., calcium or potassium). Because each endocrine gland has a rich supply of blood, each gland is able to detect small changes in the concentrations of its regulating substances.
Some endocrine glands are controlled by a simple negative feedback mechanism. For example, negative feedback signaling mechanisms in the parathyroid glands (located in the neck) rely on the binding activity of calcium-sensitive receptors that are located on the surface of parathyroid cells. Decreased serum calcium concentrations result in decreased calcium receptor binding activity that stimulates the secretion of parathormone from the parathyroid glands. The increased serum concentration of parathormone stimulates bone resorption (breakdown) to release calcium into the blood and reabsorption of calcium in the kidney to retain calcium in the blood, thereby restoring serum calcium concentrations to normal levels. In contrast, increased serum calcium concentrations result in increased calcium receptor-binding activity and inhibition of parathormone secretion by the parathyroid glands. This allows serum calcium concentrations to decrease to normal levels. Therefore, in people with normal parathyroid glands, serum calcium concentrations are maintained within a very narrow range even in the presence of large changes in calcium intake or excessive losses of calcium from the body.
Control of Hormone Release
Hormone levels in the blood are maintained by negative feedbackA stimulus or low hormone levels in the blood triggers the release of more hormoneHormone release stops once an appropriate level in the blood is reached
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