Hormones PDF

Chapter two Hormone Introduction: Hormones are chemical substances synthesized and produced by the specialized glands to control and regulate the activity of certain cells and organs. These specialized glands are known as endocrine glands. Hormones are chemical substan...

Chapter two Hormone Introduction: Hormones are chemical substances synthesized and produced by the specialized glands to control and regulate the activity of certain cells and organs. These specialized glands are known as endocrine glands. Hormones are chemical substances that essentially function as messengers of the body. These substances are secreted by special glands known as the endocrine glands. These endocrine glands are distributed throughout the body. These messengers control many physiological functions as well as psychological health. They are also quite important in maintaining homeostasis in the body. Glands Glands are important organs located throughout the body. They produce and release substances that perform certain functions. The body has many glands throughout it, they fall into two types: endocrine and exocrine. Types of glands Endocrine and exocrine glands serve very different purposes in the body. Endocrine glands Endocrine glands are part of endocrine system. They make hormones and release them into bloodstream such as (adrenal glands, pituitary gland, hypothalamus, thyroid, pineal gland). These hormones control a number of important functions in the body, such as (growth and development, metabolism, mood, reproduction) 1 Exocrine glands Exocrine glands produce other substances — not hormones — that are released through ducts to the exterior of the body, such as sweat, saliva, and tears. Two systems act individually and together in regulating an animal’s physiology 1- Endocrine system The endocrine system consists of several endocrine glands plus many hormone- secreting cells in organs that have functions besides secreting hormones. It acts through chemical messengers- hormones–carried in the circulation 2 Nervous system The nervous system, which controls body activities through the release of neurotransmitters at synapses, The nervous system transmits electrochemical signals between the brain and peripheral tissues for coordinating the diverse body functions. The nervous system and endocrine system often work together. For example, certain parts of the nervous system stimulate or inhibit the release of hormones by the 3 endocrine system. Typically, the endocrine system acts more slowly than the nervous system. Cell Signaling The effects of hormones depend on how they are released. Hence, signalling effects can be classified into the following: 1-Autocrine: The hormone act on the cell that secreted it. 2-Paracrine: The hormone act on a nearby cell without having to enter the blood circulation. 3-Intracrine: The hormone is produced in the cell and acts intracellularly means inside the cell. 4-Endocrine: The hormone act on the target cells once it is released from the respective glands into the bloodstream. 5-Neurocrine: involving secretions of peptides into the blood from specialized neurons 4 Hormone receptors Cell-associated recognition molecules which are protein in nature Functional sites: Two functional sites Recognition site: It binds the hormone specifically. Signaling site: It couples hormone binding to intracellular effect Hormone receptors Location: Receptors may be: 1. Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis. Recall that mRNA carries genetic information from the DNA in a cell‘s nucleus out to the ribosome, where the protein is assembled. 5 2.Cell-surface receptors, also known as transmembrane receptors, are proteins that are found attached to the cell membrane. These receptors bind to external ligand molecules (ligands that do not travel across the cell membrane). This type of receptor spans the plasma membrane and performs signal transduction, in which an extracellular signal is converted into an intercellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Classification of Hormone Hormone ca be classified according to A. chemical nature B. Mechanism of action 6 A. Classification of Hormones according to chemical nature: 1-Amino Acid-Derived Hormones These are derived from amino acid tyrosine, e.g. epinephrine, norepinephrine and thyroid hormones. 2. Peptide/Protein hormones: These are either large proteins or small or medium size peptides, e.g. Insulin, glucagon, parathormone, calcitonin, pituitary hormones, etc. 3. Steroid hormones: These are steroid in nature derived from cholesterol such as adrenocorticosteroid hormones, androgens, estrogens and progesterone. 4. Fatty acid derivatives – Eicosanoids 7 8 B. Mechanism of action 1. Hormone which bind to intra cellular receptor 2. Hormone which bind to membrane receptor functions of hormones Following are some important functions of hormones: Food metabolism. Growth and development. Controlling thirst and hunger. Maintaining body temperature. Regulating mood and cognitive functions. Initiating and maintaining sexual development and reproduction. 9 Mechanism of Hormone Action Hormones The function of different hormones is to control the activity of levels of targe tissues. To achieve this, the hormones may alter either the permeability of the cell or they may activate some other specific cellular mechanism. Mechanism of Hormone Action Hormones are divided in terms of their effect on the cell into two main types: 1-Activation of enzymes hormones that perform their work through metaphases on the cell's dinner (surface receptors) without entering the cytoplasm of the cell such as peptide hormones as well as the hormone epinephrine and prostaglandins, perform their function by directly affecting surface receptors through the second messenger system theory. 10 2-Modulation of gene expression Hormones that can cross the membrane (e.g. steroid hormones) bind to the receptor inside the cell, at the cytoplasm, or they will enter the nucleus and bind to the receptor at the nucleus and initiate transcription). 11 Transport of hormones Polypeptides and catechol hormones are characterized by their solubility in blood serum, where they are transported in the blood in their free unbound form, while steroid hormones and thyroid hormones have less solubility in the blood, and therefore they are associated with certain transport proteins(sex hormone binding globulin (SHBG), which carries estradiol and testosterone and corticosteroid binding globulin (CBG), which carries glucocorticoids) , in addition to the presence of a very low percentage of free. in a form changing the pattern of hormone secretion Hormone secretions vary and are not regular or equal during the hours of one day, so hormone secretion is related to the need for it, as well as the degree of its disposal. The secretion of the cortisol hormone follows a special pattern during the hours of the day and night, with its highest concentration in the blood in the morning (8-10 am), as well as the ACTH hormone in it While the highest concentration of growth hormone in hours of sleep. Regulation hormones secretion A-Feedback mechanism Hormones control many cell activities, so they are very important for homeostasis. But what controls the hormones themselves? Most hormones are regulated by feedback mechanisms. A feedback mechanism is a loop in which a product feeds back to control its own production. Most hormone feedback mechanisms involve negative feedback loops. Negative feedback keeps the concentration of a hormone within a narrow range. Negative Feedback Negative feedback occurs when a product feeds back to decrease its own production. This type of feedback brings things back to normal whenever they start to become too extreme. The thyroid gland is a good example of this type of regulation. It is controlled by the negative feedback loop Here‘s how thyroid regulation works. The hypothalamus secretes thyrotropin-releasing hormone, or TRH. TRH stimulates the pituitary gland to produce thyroid-stimulating 12 hormone, or TSH. TSH, in turn, stimulates the thyroid gland to secrete its hormones. When the level of thyroid hormones is high enough, the hormones feedback to stop the hypothalamus from secreting TRH and the pituitary from secreting TSH. Without the stimulation of TSH, the thyroid gland stops secreting its hormones. Soon, the level of thyroid hormone starts to fall too low. B-metabolism regulation There are many hormones that are not subject to the body's pivotal relationship to the hypothalamus and pituitary, and are not related to them. It is directly affected by 13 the concentration of the metabolic component that the hormone regulates its concentration inside the body. For example, in normal conditions, the concentration of glucose in the body is regulated by two hormones: insulin, which is secreted when the level of glucose in the blood rises from the normal level, and reduces this level, and glucagon is secreted when the level of glucose decreases. And it increases it as well when the concentration of calcium in the body decreases, the PTH hormone is secreted to increase its concentration in the bloo 14 Hypothalamus and Pituitary Gland Hypothalamus regulates the pituitary gland‘s secretions. Pituitary gland is responsible for secreting nine hormones. Divided into a posterior and anterior portion. Posterior pituitary is also known as the neurohypophysis, because it is continuous with the brain. Anterior pituitary is also known as the adenohypophysis, because it acts more as a gland. 15 16 1-Thyroid Stimulate Hormone (TSH) It is secreted from the basal pituitary cells called (thyrotropha) and is considered one of the glycoprotein hormones, where carbohydrates make up about 7-8% of its chemical composition Function of hormone This hormone performs a major and important function in stimulating the growth of the thyroid gland, activating its secretion of thyroxine (T4) and triiodothyronine (T3), and ensuring blood supply to the thyroid gland. 17 2-Adrenocorticotropin hormone (ACTH) It is secreted from the basal pituitary cells called Corticotrophs. This hormone contains a long chain consisting of 39 amino acids. The half- life of the hormone (t1/2) is about 20 minutes. ACTH function ACTH secretion is subject to direct regulation of the hypothalamic releasing hormone (CRH), which directly affects the cortical part of the adrenal glands to secrete glucocorticoids, especially cortisol, and thus regulates the metabolism of glucose, protein, and fat. Also, it helps to increase the entry of glucose into the cell in addition to stimulating the process of glycogenolysis in order to provide the energy needed to manufacture Hormones and also helps in the formation of glucose from carbohydrate and protein sources. 3-Follicular Stimulating Hormone (FSH) Although the naming of this hormone indicates its role in stimulating the growth of ovarian follicles, its role is essential and important in both males and females. Function Hormone FSH performs important functions in both the female and the male, which can be summarized as follows: (a) In the female 1-The female needs this hormone for ovarian growth during the premenstrual period banishment maturation as well as growth and development of ovarian follicles 2- It plays an essential role in maintaining the secretion of estrogen hormone The corpus luteum of the number of animals from. 3- It regulates the growth of ovarian follicles during the reproductive cycle (b) In the male: 1-The male needs this hormone to growth and develop into the seminiferous tubules 2- The testicles in preparation for the formation of sperm. 3-it is regulating the mechanism of manufacturing and formation of sperm cells in sexually mature animals. 18 4 - Luteinizing Homone (LH) It is called the ovulation hormone because of its importance to carry out this function alone, but through the name that is called it hormone function LH plays an important role in female and male reproductive activity It is summarized in the following: (1) In the female It supports (Synergize) the FSH hormone in accelerating the FSH The process of maturation and development of the ovarian follicles and the oocyte. It plays an essential role in the secretion of estrogen by theca interna cells, as well as Granulosa cells 5-Growth hormone (GH) Growth hormone (GH), peptide hormone secreted by the anterior lobe of the pituitary gland. It stimulates the growth of essentially all tissues of the body, including bone. GH is synthesized and secreted by anterior pituitary cells called somatotrophs, which release between one and two milligrams of the hormone each day. GH is vital for normal physical growth in children; its levels rise progressively during childhood and peak during the growth spurt that occurs in puberty. Growth hormone deficiency GH deficiency is one of the many causes of short stature and dwarfism. It results primarily from damage to the hypothalamus or to the pituitary gland during fetal development (congenital GH deficiency) or following birth (acquired GH deficiency). GH deficiency may also be caused by mutations in genes that regulate its synthesis and secretion. Affected genes include PIT-1 (pituitary-specific transcription factor-1) and POUF-1 (prophet of PIT-1). Mutations in these genes may also cause decreased synthesis and secretion of other pituitary hormones. 6 - prolactin hormone 19 chemical composition The hormone that stimulates milk production, is a protein of 198 amino acids that is produced in the acidophilic cells of the anterior pituitary. Its molecular weight is (22550) Daltons, and it contains sulfide bonds, two of which are in the same positions as those in both growth hormone GH and human chorionic gonadotrophin. Function of hormone The main function of the prolactin hormone is to stimulate the mammary gland to secrete milk and continue to produce milk. Its secretion is the development and growth of the breast tissue before pregnancy under the control of the three hormones, estrogen, progesterone and protection,. The absence of the prolactin hormone leads to, the hormones estrogen and progesterone are ineffective in growth of the breast tissue. Posterior pituitary hormones Neurohypophysis hormones (posterior pituitary hormones) Gland under the hypothalamus in humans. There are two protein hormones: Vasopressin and oxytocin. These multi-hormones are formed in hypothalamic neurons in the paraventricular and supraoptic in the form of large molecules hormone generators(pro-hormone). As a result of the action of a proteolytic enzyme(protease), oxytocin and Vasopressin are separated and the remaining parts of their hormonal generators are called neurophysins, which act as protein carriers for both hormones. They communicate with oxytocin and vasopressin noncovalently. Vasopressin-neurophysin I These complexes (hormone-neurophysin) are transmitted in membranous vesicles through the fibrous axons of hypothalamic neurons to the posterior pituitary gland, neurohypophysis, where the nerve endings are stored in storage granules. The half- life of the hormones Vasopressin and Oxytocin is about five minutes, and the kidney acts as a main side for the excretion of the two hormones. 20  The hormones Vasopressin and Oxytocin are peptide with 9 amino acids which differ in type of amino acids in locations 3 and 8. their molecular weight is about 1000. 7-Vasopressin (VP) Vasopressin hormone also is called Antidiuretic hormone(ADH) The secretion of the vasopressin The secretion of the vasopressin hormone is influenced by many stimuli: 1-the lack of pressure Osmotic pressure 2- The volume of blood circulating in the veins (the decrease in blood volume is more than 8%), as the bleeding stimulates the secretion of vasopressin, as the increase in the hormone has the effect on Vasoconstrictor. 3- Hypotension (low blood pressure). 4-Emotional stress and nausea. 5- Narcotic drugs such as nicotine and morphine. 6- Effort, pain, sleep and sports. Function of hormone 1-The main work of the VP hormone is to maintain water in the living body, as it increases the process of water absorption in the urinary tubes, and thus restores this water to the blood, and thus works to balance water in the body and control its loss. 2-also works to contract the smooth muscles. Smooth muscle contraction. 8-Oxytocin Oxytocin secretes from the posteror of pituitary in response to the stimulation arising from the process of breast sucking and the hormone causes contraction of the uterus as well as the tissues surrounding the milky tubes in the breast. These cells increase for the hormone during pregnancy and during childbirth. 21  One of the activities of the hormone increases the uterine sensitivity of this movement during it sexual intercourse. The stress inhibits the secretion of the hormone oxytocin and thus reduces the flow of milk. Thyroid gland: Thyroid gland is an endocrine gland, found in the neck are one of the most important glands. This gland uses iodine, a trace element which is not produced in the body and must be ingested, and tyrosine to manufacture T3 and T4. The majority of production is T4 which is converted in target tissues to the active form T3. 22 Thyroid gland functions The thyroid gland functions is to produce, storage and secretion of the two related thyroid hormones, triiodothyronine (T3) and thyroxine (T4), (both iodinated derivatives of tyrosine, and calcitonin, a hormone of uncertain function), which responsible to stimulate macromolecule metabolism of fats, proteins, and carbohydrates, and in the development and maintenance of both mental and physical function in most tissues Regulation of thyroid hormone secretion The components of the hypothalamic– pituitary–thyroid axis are Thyroid hormones (TH), Thyroid stimulating hormone (TSH), and Thyrotropin-releasing hormone (TRH). Thyroid stimulating hormone stimulates the synthesis and secretion of the triiodothyronine and thyroxine by the thyroid gland. The TRH, a tripeptide, is secreted by the hypothalamus and in turn causes the synthesis of a large glycoprotein hormone, TSH, from the anterior pituitary. Release of TRH in turn depends on blood levels of thyroid hormones; which inhibit secretion of TRH via negative feedback. There is no thyrotropin-inhibiting hormone. 23 Regulation of secretion and actions of thyroid hormones Degradation Only free T3 and free T4 can enter cells to exert their actions. T4 is deiodinated to T3 in many cells of the body, particularly the liver and kidneys.The thyroid secretes 90% T4, with 50% of this being deiodinated to T3. The remainder is converted to reverse T3 (rT3). This is an inactive form of T3, and so creation of it is a regulatory mechanism. More rT3 is created when the body needs to reduce the action of T3 and T4. The hormones are further deiodinated to diiodothyronine and monoiodothyronine in the liver and kidneys. Iodine is recycled or excreted in the urine 24 Diagnosis of thyroid function Biochemical measurement in the diagnosis of thyroid disease have traditionally been known as ‗thyroid function tests‘. Measurement levels of TSH, T4 and T3 in blood by ELISA or by RIA (radio immuno assay) form the basis of laboratory diagnosis of thyroid diseases. i. In hypothyroidism, both thyroid hormone T3 and T4 are reduced; but TSH levels are increased due to lack of feedback effect. ii. In hyperthyroidism, T3 and T4 levels are increased, while TSH is reduced due to feedback inhibition. iii. But when hypothyroidism is due to hypothalamic or pituitary defect, then TSH, T 3 and T4, all are decreased. The concentration of free T3 and T4, and TSH are measured and their serum normal concentrations are Free triiodothyronine (T3) ---------------- 60 -120 nmol / L (80 -220 ng/dl) Free thyroxine (T4) ---------------------- 0.92- 2.33 nmol /L (0.8-2.4 ng/dl) Total thyroxine (T4) ---------------------- 5-12 µg/dl Thyroid stimulating hormone (TSH)----- 0.25 -5.0 nmol / L (