The Endocrine System

The Endocrine System Endocrine system Endocrine glands consist of groups of secretary cells surrounded by an extensive network of capillaries that facilitates diffusion of hormones from the secretary cells in to the bloodstream. They are commonly referred to as ductless glands because the hormones diffuse directly into the bloodstream. The hormones is then carried in the bloodstream to target tissues and organs that may be quite distant, where they influence cellular growth and metabolism. A hormone is a mediator molecule that is released in one part of the body but regulates activity of cells in other parts of the body. Endocrine system Homeostasis of the internal environment is maintained partly by the autonomic nervous system and partly by the endocrine system. The autonomic nervous system is concerned with rapid changes, while hormones of the endocrine system are mainly involved in slower and more precise adjustment. The endocrine include : The pituitary gland Thyroid gland Parathyroid gland Adrenal gland Pineal gland Endocrine system In addition several organs and tissues are not endocrine glands but contain cells that secrete hormones. These includes: Hypothalamus Thymus Pancreas Ovaries Testes Kidney All endocrine glands and hormone – secreting cells constitute the endocrine system. The science of the structure and function of the endocrine glands and diagnosis and treatment of disorders of the endocrine system is called endocrinology Endocrine system When a hormone arrives at its target cell, it binds to a specific area, the receptor. The receptors for water soluble hormones are situated on the cell membrane and those for lipid soluble hormones are inside the cells. Basic categories of hormones Water soluble hormones-Amino acid based: modified amino acids (or amines For eg: epinephrine and norepinephrine), peptides (Insulin and growth hormone), and proteins (Prostaglandins etc. ) Lipid soluble hormones-Steroid hormones and thyroid hormones Endocrine system A hormone is released in response to a specific stimulus and usually its action reverses the stimulus through a negative feedback mechanism. This may be controlled either indirectly through the release of hormones by the hypothalamus and the anterior pituitary gland e.g steroid and thyroid hormones, or directly by blood levels of the stimulus. E.g Insulin and glucagon. The effect of a positive feedback mechanism of the stimulus and increasing release of the hormone until a particular process is complete and the stimulus ceases e.g release of oxytocin during labour. Endocrine system Hormone Transport in the blood Most water – soluble hormone molecules circulate in the watery blood plasma in a free form , whereas most lipidsoluble hormone molecules are bound to transport proteins. The transport proteins , which are synthesized by cells in the liver , have three functions: 1. They make lipid-soluble hormones temporarily water soluble, thus increasing their solubility in blood. 2. They retard passage of small hormone molecule through the filtering mechanism in the kidneys, thus slowing the rate of hormones loss in the urine. 3. They provide a ready reserve of hormone, already present in a the blood stream . Endocrine system Control of hormone secretion When the endocrine gland is stimulated. It release hormone, increasing the concentration of hormone in the blood. In the absence of stimulation , the blood level of the hormone decreases. Regulation of secretion normally prevents overproduction and underproduction of any given hormone. Hormone secretion is regulated by 1) Signals from the nervous system 2) Chemical changes in the blood 3) Other hormones For eg: Nerve impulse to the adrenal medulla regulate the release of epinephrine Blood Ca2+ level regulates the secretion of parathyroid hormone A hormone from the anterior pituitary (ACTH) stimulates the release of cortisol by the adrenal cortex. Pituitary gland and hypothalamus The pituitary gland and hypothalamus act as a unit , regulating the activity of most of the other endocrine glands. So ., it is called master endocrine gland . The pituitary gland lies in the hypophyseal fossa of the sphenoid bone below the hypothalamus , to which it is attached by a stalk. It is the size of a pea, weighs about 500 mg and consists of three distinct parts that originate from different types of cells. The anterior pituitary is an upgrowth of glandular epithelium from the pharynx and the posterior pituitary is a downgrowth of nervous tissue from the brain. There is a network of nerve fibers between the hypothalamus and the posterior pituitary. Between these lobes there is a thin strip of tissue called the intermediate lobe and its function in human is not known. Pituitary gland and hypothalamus Anterior Pituitary gland The anterior pituitary secretes hormones that regulate a wide range of bodily activities, from growth to reproduction. Release of anterior pituitary hormones is stimulated by releasing hormones and suppressed by inhibiting hormones from the hypothalamus. Thus the hypothalamus are an important link between the nervous and endocrine system. Hypothalamic hormones reach the anterior pituitary through a portal system . The heart passes from the heart through an artery to a capillary to a vein and back to the heart. In a portal system, blood flows from one capillary network into a portal vein and then into a second capillary network without passing through the heart. The name of the portal system gives the location of the second capillary network. Anterior Pituitary gland In hypophyseal portal system , blood flows from capillary in the hypothalamus into portal veins that carry blood to capillaries of the anterior pituitary. The Blood transports releasing and inhibiting hormones secreted by the hypothalamus. These hormones influence secretion and release of other hormones formed in the anterior pituitary. Anterior Pituitary gland The releasing and inhibiting hormones that stimulate and inhibit secretion of specific anterior hormones. The whole system is controlled by a negative feedback mechanism. When there is a low level of a hormone in the blood supplying the hypothalamus , it produces the appropriate releasing hormone that simulates release of a trophic hormone by the anterior pituitary. This in turn stimulates the target gland to produce and release its hormone. As a result the blood level of that hormone rises and inhibits the secretion of releasing factor by hypothalamus. Anterior Pituitary gland Anterior Pituitary gland Hormones of the hypothalamus, anterior pituitary and their target tissues Hypothalamus Anterior pituitary Target gland / Tissues GHRH (Growth Hormone Releasing Hormone) GH (Growth Hormone) Most tissues Many organs GHRIH (Growth Hormone Releasing Inhibiting Hormone GH inhibition TSH Inhibition Thyroid gland Pancreatic islets Most Tissues TRH (Thyroid releasing Hormone) TSH (Thyroid stimulating hormone) Thyroid gland CRH (Corticotrophin releasing Hormone) ACTH (Adrenocorticotrophic Hormone) Adrenal cortex PRH (Prolactin releasing Hormone) PRL (Prolactin Hormone) Breast PIH (Prolactin Inhibiting Hormone) PRL inhibition Breast LHRH / GnRH (Luteinsing Hormone releasing Hormone)/ (Gonadotrophin releasing Hormone) FSH, LH ( Follicle stimulating Hormone), (Luteinsing Hormone) Ovaries and Testes Ovaries and Testes Anterior Pituitary gland Growth Hormone This is the most abundant hormone synthesized by anterior pituitary. Functions It stimulates growth and division of most body cells specially in bones and skeletal muscle. Growth hormone increases the growth rate of skeleton and skeletal muscles during childhood and teenage years. In adults , growth hormone help to maintain the mass of muscles and bones It promotes healing of injuries and tissue repair. It also regulates the metabolism in many organs for eg: Liver, intestine and pancreas,. It stimulates the protein synthesis It promotes breakdown of fats and increases blood glucose levels. Anterior Pituitary gland Growth Hormone Its release is stimulated by growth hormone releasing hormone and suppressed by growth hormone release inhibiting hormone both of which are secreted by the hypothalamus. Secretion of GH is greatest at night during sleep and is also stimulated by hypoglycemic, exercise and anxiety. The daily amount secreted peaks in adolescence and then declines with age. Inhibition of GH secretion occurs by a negative feedback mechanism when the blood level rises and also when GHRIH (somatostatin) is released by the hypothalamus GHRIH also suppresses secretion of TSH and gastrointestinal secretion, e.g : gastric juice , gastrin and cholecystokinin. Anterior Pituitary gland Thyroid stimulating Hormone (TSH) This hormone is synthesized by the anterior pituitary and its release is stimulated by TRH ( Thyrotrophin- releasing hormone) from the hypothalamus. TSH stimulates growth and activity of thyroid gland TSH stimulates the synthesis and secretion of the two thyroid hormone , T3 ( triiodothyronine) and T4 (thyroxine), both are produced by the thyroid gland. TRH ( Thyrotrophin- releasing hormone) from the hypothalamus controls TSH secretion. Release of TRH depends on T3 and T4, which inhibit secretion of TRH via negative feedback. When the blood level of thyroid hormone is high , secretion of TSH is reduced and vice- versa. There is no thyrotrophin – inhibiting hormone. Release its lower in early evening and highest during the night. Anterior Pituitary gland Adrenocorticotrophic Hormone ( Corticotrophin, ACTH) Anterior Pituitary gland Corticotrophin releasing hormone (CRH) from the hypothalamus promotes the synthesis and release of ACTH by the anterior pituitary. And ACTH controls the production and secretion of cortisol and other glucocorticoids by the cortex of the adrenal glands. ACTH levels are highest at about 8AM and fall to their lower about midnight, although high levels some times occur at midday and 6 PM. It is associated with the sleep pattern and adjustment to changes takes several days, following e.g ., changing work shifts , traveling to a different time zone. Secretion is also regulated by a negative feedback mechanism . It is being suppressed when the level of ACTH and CRH is increased. The factor which can stimulate secretion include low blood glucose , physical trauma, exercise, emotional states, and fever etc. Anterior Pituitary gland Prolactin Prolactin , together with other hormones , initiates and maintains milk secretion by the mammary glands. Ejection of milk from the mammary glands depends on the hormone oxytocin, which is released from the posterior pituitary. Together milk secretion and ejection constitute lactation. Prolactin stimulates lactation ( milk production) And has a direct effect on the breasts immediately after parturition( childbirth). The hypothalamus secrets both inhibitory and excitatory hormones that regulates prolactin secretion. The blood level of prolactin PRH ( Prolactin releasing hormone) and is lowered by PIH( prolactin Inhibiting Hormone) ( dopamine). Anterior Pituitary gland After birth suckling stimulates prolactin secretion and lactation. . High blood level of prolactin reduces the chances of conception during lactation. During the menstruation the blood level of prolactin decreases. Hyper secretion of prolactin in males cause erectile dysfunction. In females hyper secretion of prolactin causes galactorrhoea ( inappropriate lactation) and amenorrhea . Prolactin secretion is related to sleep i.e it is raised during any period of sleep, night and day. Emotional stress increases the prolactin production. Anterior Pituitary gland Gonadotrophins After puberty two gonadotrophins ( sex hormones) are secreted by the anterior pituitary in response to LHRH( luteinsing hormone releasing hormone), also known as GnRH(gonadotrophin releasing hormone. In both males and females these are FSH ( Follicle stimulating hormone) LH (luteinsing hormone) In both the sexes FSH stimulates production of gametes ( Ova and spermatozoa). Anterior Pituitary gland FSH: In females : The ovaries are targets for follicle stimulating hormone. FSH stimulates the secretion of estrogen. During the menstrual cycle. IN males: FSH stimulates the production of sperm in testes. GnRH from the hypothalamus stimulates the FSH release. The release of GnRH and FSH is suppressed by estrogen in females and by testosterone in males through negative feedback mechanism. There is no gonadotrophin inhibiting hormone. Anterior Pituitary gland LH ( Luteinizing Hormone): In females: It triggers ovulation. LH also stimulate the formation of corpus luteum. In males: LH stimulates the testes to secrete the testosterone. Secretion of LH is also controlled by the GnRH. FSH and LH both stimulates the secretion of estrogen by ovarian cells in females. Posterior Pituitary. Posterior pituitary does not synthesize hormones , it does stores and release two hormone. This is formed nervous tissue and consist of nerve cells surrounded by supporting cells called pituicytes. These neurons have their cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus and their axons form a bundle known as hypothalamohypophyseal tract. The posterior pituitary secrets one of the two hormones Oxytocin Antidiuretic hormone. Posterior pituitary hormones are synthesized in the nerve cell bodies, transported along the axons and then stored in vesicles within the axon terminals within the posterior pituitary. Their release by exocytosis is triggered by nerve impulses from the hypothalamus. Oxytocin: During and after delivery of a baby, oxytocin affects two target tissues : The mother’s uterus and breasts. During delivery , oxytocin enhances contraction of smooth muscle cells in the wall of the uterus, after delivery , it stimulates milk ejection. The function of oxytocin in males and non pregnant females is not clear. Milk Ejection: The process of milk ejection also involve a positive feed back mechanism . Suckling generates sensory impulses that are transmitted from the breasts to the hypothalamus . The impulse trigger the release of oxytocin from the posterior pituitary and oxytocin stimulates contraction of lactating breasts, ejecting milk. Suckling also inhibits the release of PIH ( Prolactin Releasing Hormone), prolonging prolactin secretion and lactation. During Delivery Antidiuretic Hormone: Antidiuretic hormone that decrease urine production. ADH secretion causes the kidneys to return more water to the blood , and decreasing the urine volume. In the absence of ADH, urine output is increased from the normal. ADH also decreases the water loses through sweating and cause the constriction of arterioles, which increases blood pressure. As the osmotic pressure rises, the secretion of ADH increases. More water is therefore reabsorbed and the urine output is reduced. This means that the body retains more water and the rise in osmotic pressure is reversed. Conversely, when the osmotic pressure of the blood is low, for example: After a large fluid intake, secretion of ADH is reduced, less water is reabsorbed and more urine is produced. At high concentration , for example after severe blood loss, ADH causes smooth muscle contraction, especially vasoconstriction in the blood vessels of the skin and abdominal organs. This cause raise in systemic blood pressure. Thyroid Gland The butterfly shaped thyroid gland is located just inferior to the larynx. It is composed of right and left lobes, one on either side of the thyroid cartilage. It is highly vascular that weighs about 25g and is surrounded by a fibrous capsule. The lobes are joined by a narrow isthmus, lying in front of the trachea. Microscopic spherical sacs called thyroid follicles make up most of the thyroid gland. The wall of each follicle consists primarily of cells called follicular cells. Between the follicles there are other cells found singly or in small groups : parafollicular cells, also called C-cells, which secrete the hormone calcitonin. Two parathyroid gland lie against the posterior surface of each lobe and sometimes embedded in thyroid tissue. The follicular cells produce two hormones Thyroxine ( T4 or tetraiodothyronine) Triiodothyronine (T3) Parafollicular cells produce hormone: Calcitonin ( help to regulate calcium homeostasis) Thyroxine and tri-iodothyronine: Iodine is essential for the formation of thyroid gland hormones, thyroxine ( T4) and triiodothyronine(T3). The body’s main source of iodine are seafood , vegetables grown in iodine-rich soil and iodinated table salt in the diet. The thyroid gland selectivity takes up iodine from the blood, a process called iodine trapping. The thyroid hormones are synthesized as large precursor molecule called thyroglobulin, the major constituent of colloid . The release of T3 and T4 into blood is regulated by TSH (thyroid stimulating hormone) from the anterior pituitary. When the supply of iodine is deficient, Excess TSH is secreted and there is proliferation of thyroid gland and enlargement of the gland. Secretion of T3 and T4 begins about the third month of fetal life and is increased at puberty and in women during the reproductive years. Otherwise it remains, constant throughout life., Thyroid hormones enter the target cells and regulate the expression of genes in the nucleus, i.e they increase or decrease the synthesis of some proteins including enzymes. They combine with specific receptor sites and enhance the effects of other hormones. E.g- adrenaline and noradrenaline. T3 and T4 affect most cells of the body by: Increasing the basal metabolic rate and heat production Regulating metabolism of carbohydrate , proteins and fats. Uses T3 and T4 are essential for normal growth and development of the skeleton and nervous system. Other uses see in table Calcitonin: This hormone is secreted by the parafollicular cells or C- cells in the thyroid gland. It acts on bone and the kidneys to reduce the blood calcium level when it is raised and reduces the reabsorption of calcium from the bones and inhibits reabsorption of calcium by the renal tubules. Its effect is opposite to that of parathyroid hormone, the hormone secreted by the parathyroid glands. Release of calcitonin is stimulate by increase in the blood calcium level. This hormone is important during childhood when bones undergo considerable changes in size and shape. Parathyroid Gland There are four small parathyroid glands, embedded in the posterior surface of the lobe of thyroid gland and are small , rounded mass of tissue called parathyroid glands. Each gland has a mass of about 40 mg. One superior and one inferior parathyroid gland are attached to each lateral lobe. Function The parathyroid glands secrete parathyroid hormone (PTH). Secretion is regulated by the blood level of calcium. When this falls, secretion of PTH is increased and vice versa. To increase the blood calcium level when it is low.( The level is increased by indirectly increasing the amount of calcium absorbed from the small intestine and reabsorbed from the renal tubules. If it is inadequate , then PTH stimulates osteoclast and reabsorption of calcium from bones. PTH and calcitonin is needed for: Muscle contraction Blood clotting Nerve impulse transmission. Adrenal Glands There are two adrenal glands, one situated on each kidney. In an adult, each adrenal gland is 3-5cm in height, 2-3cm in width, and a little less than 1 cm thick. The glands are composed of two parts which have different structures and functions. The outer part is the cortex and the inner part the medulla. The adrenal cortex is essential to life because it produces steroid hormones. Complete loss of adrenocortical hormones leads to death due to dehydration and electrolyte imbalances , unless hormone replacement therapy begins. The adrenal medulla produces three catecholamine : Norepinephrine , epinephrine and small amount of dopamine. Adrenal Glands Adrenal cortex The adrenal cortex produces three steroids called adrenocorticocoids. They are: a) Glucocorticoids b) Mineralocorticoids c) Sex Hormones ( androgens) a) Glucocorticoids The Glucocorticoids, regulates metabolism and resistance to stress, include cortisol ( hydrocortisone), corticostrone and cortisone. Out of three , cortisol is the most abundant, and accounting for 95% of glucocorticoid activity. Control of glucocorticoid secretion is by negative feedback system. Low blood levels of Glucocorticoids, mainly cortisol stimulate hypothalamus to secrete corticotrophin- releasing hormone (CRH) CRH promotes the release of ACTH from the anterior pituitary. Stress and ACTH flows in the blood to the adrenal cortex, where it stimulates Glucocorticoids secretion . To a much smaller extent, ACTH also stimulates secretion of aldosterone. In non-stressful conditions, secretion has marked circadian variations. The highest level of hormones occurs between 4AM and 8AM and the lowest, between midnight and 3AM. When the sleeping and waking pattern is changed , it takes several days for adjustment of the ACTH/ cortisol secretion to take place. Glucocorticoids has the following effects: 1. 2. 3. 4. 5. 6. 7. Gluconeogenesis and hyperglycemia LIpolysis Stimulating breakdown of proteins Promoting absorption of sodium and water from renal tubules. Anti-inflammatory actions Suppression of immune responses Delayed wound healing. Mineralocorticoids Aldosterone is the major mineralocorticoids. It regulates homeostasis of two mineral ions, namely sodium and potassium, and helps adjust blood pressure and blood volume. Its functions are mainly maintenance of water and electrolyte balance in the body. It stimulates reabsorption of sodium and excretion of potassium in the urine. The blood potassium level regulates the amount of aldosterone produced by adrenal cortex. When the potassium level rises, the secretion of aldosterone is more. Renin-angiotensin system also play an important role in release of aldosterone. (See diagram ) Sex Hormones: In both males and females, the adrenal cortex secrets small amount of androgen and the quantity is so low that their effects are insignificant. This hormone is secreted in large quantity after puberty. Adrenal medulla The medulla is completely surrounded by the adrenal cortex. It develops from nervous tissue in the embryo and is a part of sympathetic division of the autonomic nervous system. It produce the hormones adrenaline and noradrenaline. Adrenaline and Noradrenaline Noradrenaline is the postgangoilinic neurotransmitter of the sympathetic division of the autonomic nervous system. Adrenaline and some noradrenaline are released into the blood from the adrenal medulla during stimulation of the sympathetic nervous system. They together potentiate the fight and flight response by Increasing heart rate Increasing blood pressure Increasing metabolic rate Dilating the pupil Adrenaline has a greater effect on the heart and metabolic processes whereas noradrenaline has more influence on blood vessels. The short term or immediate response is prepared for fight and flight. In the longer term , ACTH from the anterior pituitary stimulates the release of glucocorticoids and mineralocorticoids from the adrenal cortex and a more prolong response to stress. Pancreatic Islet The pancreas is both an endocrine gland and an exocrine gland. Unlike the exocrine pancreas, which produces pancreatic juices, there are no ducts .Pancreatic hormones are secreted directly into the bloodstream and circulate throughout the body. There are three main types of cells in the pancreatic islets: α (alpha) cells , which secrets glucagon β( beta) cells , which secrets insulin. δ ( delta) cells, which secrete somatostatin (GHRIH) The normal blood glucose level is between 3.5 an 8mmol/litre (63to 144mg/100ml). Blood glucose levels are controlled mainly by the opposing actions of insulin and glucagon: Glucagon increases blood glucose levels Insulin reduces blood glucose levels. Insulin: Insulin is a polypeptide consisting of about 50 amino acids. Glucagon raises blood glucose level, insulin lowers it. Somatostatin inhibits both insulin and glucagon release . Regulation of glucagon and insulin secretion Insulin Insulin is a polypeptide consisting of about 50 amino acids. The main functions of insulin is to lower raised blood nutrient levels, especially glucose but also amino acids and fatty acids. When these nutrients are in excess , insulin promotes their storage by: Acting on the cell membrane and stimulating uptake and use of glucose by muscle and connective tissue cells. Increasing conversion of glucose to glycogen, especially in the liver and skeletal muscle. Accelerating uptake of amino acids by cells, and the synthesis of protein Promoting synthesis of fatty acids and storage of fat in adipose tissue. Decreasing glycogenolysis Preventing the breakdown of protein and fat and help in gluconeogenesis. Insulin Secretion is stimulated by : Increased blood glucose levels Parasympathetic stimulation Raised blood amino acids and fatty acid level Gastrointestinal hormones ( gastrin, secretin etc.) Secretion is decreased by: Sympathetic stimulation Glucagon Adrenaline Cortisol Somatostatin Glucagon The glucagon increased blood glucose level by stimulating: Conversion of glycogen to glucose in the liver and skeletal muscle Gluconeogenesis Secretion is stimulated by: Low blood glucose level Exercise Secretion is decreased by: Somatostatin Insulin Somatostatin This hormone inhibit the secretion of both insulin and glucagon in addition to inhibiting the secretion of GH from the anterior pituitary. Pineal Gland The pineal gland is a small body attached to the roof of the third ventricle and is connected to it by a short stalk The pineal Gland is about 10mm long, is reddish brown in colour and is surrounded by a capsule. Melatonin This is a hormone secreted by the pineal gland. Secretion is controlled by daylight and level fluctuate during each 24 hours period, being highest at night and lower around midday. Secretion is influenced by the number of daylight hours i.e seasonal variations. Its function are not known but associated with coordination of circadian rhythm Inhibition of growth and development of the sex organ before puberty, possibly by preventing synthesis and releases of gonadotrophins. Thymus gland The thymus gland is located behind the sternum between the lungs. The hormone secreted by this gland is thymosin and which is required for the development of T- lymphocyte for cell mediate immunity. Some Local Hormones secreted by endocrine gland Endocrine gland secrets substances that act locally . Some are Histamine: This hormone is synthesized by the mast cells in the tissues and the basophils in blood. It plays a role in inflammation. It causes contraction of bronchi, GIT and stimulates the secretion of gastric juice. Serotonin: This is present in platelets, in the brain and in the intestinal wall. It causes intestinal secretion and contraction of smooth muscle. Some Local Hormones secreted by endocrine gland Prostaglandins: These are lipid substances and found in most tissues that act as a local hormone and the effects are: The inflammatory response Potentiating pain Fever Regulating blood pressure Blood clotting Uterine contraction during labour. Some other prostaglandins are leukotrienes and thromboxanes (platelet aggregator). Gastrointestinal Hormones: Some hormone such as gastrin , secertin and cholecystokinin influence the secretion of digestive juices and their functions.