Endocrine system PRINCIPLES OF CHEMICAL COMMUNICATION Chemical messengers - Allows cells to communicate with each other to regulate body activities; - Some produced by the nervous system, and some are produced by the endocrine system; - Most of this is produced by a specialization of cells or by a gland, which is an organ consisting of epithelial cells that specialize in secretion (controlled release of chemicals from a cell) Categories in studying Endocrine System: 1. Autocrine chemical messengers. - Stimulates the cell that originally secreted it, and sometimes nearby cells of the same type; - Ex. Those secreted by the WBC during infection; eicosanoids (prostaglandins, thromboxanes, prostacyclins, leukotrienese) 2. Paracrine chemical messengers. - Local messengers; - Produced by a wide variety of tissues and secreted into extracellular fluid; - Has a localized effect on other tissues; - Ex. Somatostatin, histamine (released during allergic reactions; stimulates vasodilation in nearby blood vessels), eicosanoids 3. Neurotransmitters. - Secreted by neurons that activate an adjacent cell, whether it is another neuron, a muscle or a glandular cell; - Secreted into a synaptic cleft, rather than into the bloodstream - Ex. Acetylcholine, epinephrine 4. Endocrine chemical messengers. - Secreted into the bloodstream by certain glands and cells, which together constitute the endocrine system - Affect cells that are distant from their source - Ex. Thyroid hormones, growth hormone, insulin, epinephrine, estrogen, progesterone, testosterone, prostaglandins FUNCTIONS OF THE ENDOCRINE SYSTEM 1. Metabolism 2. Control of food intake and digestion 3. Tissue development 4. Ion regulation 5. Water balance. 6. Heart rate and blood pressure regulation 7. Control of blood glucose and other nutrients 8. Control of reproductive functions 9. Uterine contractions and milk release 10. Immune system regulation hormones. Lipid-soluble hormones are degraded slowly and are not rapidly eliminated from the circulation. Without the binding proteins, the lipid-soluble hormones would quickly diffuse out of capillaries and be degraded by enzymes of the liver and lungs or be removed from the body by the kidneys. The breakdown products are then excreted in the urine or the bile. Water-Soluble Hormones - Polar molecules; they include protein hormones, peptide hormones, and most amino acid derivative hormones. - Quite large hormones and do not diffuse through the walls of all capillaries, therefore, they tend to diffuse from the blood into tissue spaces more slowly - Life-span: short half-lives due to the rapid degradation by the enzymes called proteases within the bloodstream CHARACTERISTICS OF THE ENDO. SYS. Endocrine System - Greek word, ‘endo’ (within); ‘krino’ (secrete) - Composed of endocrine glands and specialized endocrine cells located throughout the body; - Endocrine glands and cells secrete minute amounts of chemical messengers called hormones into the bloodstream, rather than into a duct. - Hormones then travel through the general blood circulation to target tissues or effectors - Target tissues: specific sites where hormones produce a particular response of the target tissues - Exocrine glands: have ducts that carry their secretions to the outside of the body, or into a hollow organ (stomach or intestines); ex. Saliva, sweat, breast milk, and digestive enzymes - Endocrinology: study of endocrine system HORMONES - Greek word = ‘hormon’ (to set into motion) - Regulates almost every physiological processes Two Chemical Categories: 1. Lipid-soluble hormones 2. Water-soluble hormones The entire basis of a hormone’s metabolism – its transport in the blood, its interaction with its target, and its removal from the body – is dependent on the hormone’s chemical nature. Hormone categorized based on chemical structures: 1. Steroid hormones – derived from cholesterol; 2. Thyroid hormones – derived from amino acid tyrosine; 3. Other hormones are categorized as amino acid derivatives, peptides, or proteins. Lipid Soluble Hormones - Non-polar, and include steroid hormones, thyroid hormones, and fatty acid derivative hormones - Small molecules and are insoluble in water-based fluids, such as the plasma of blood - Life-span: few days to as long as several weeks - Circulating hydrolytic enzymes can metabolize free lipid-soluble hormones Transport of Lipid-Soluble Hormones Lipid-soluble hormones travel in the bloodstream attached to binding proteins. Binding proteins transport and protect Transport of Water-Soluble Hormones They can dissolve in blood so they are delivered to their target tissue without attaching to a binding protein. Organs regulated by some protein hormones have very porous, or fenestrated, capillaries to aid in delivery of these hormone to individual cells. After degraded by the enzymes, the kidneys then filter the hormone breakdown products from the blood. Hormone target cells also destroy water-soluble hormones. Some target cells take up the hormone through endocytosis, thus terminating their effect. Once the hormones are inside the target cell, lysosomal enzymes degrade them. Often, the target cell recycles the amino acids of peptide and protein hormones and uses them to synthesize new proteins. However, some water-soluble hormones are more stable in the blood than others. In many instances, protein and peptide hormones have a carbohydrate attached to them, or their terminal ends are modified which protects them from proteases activity to a greater extent than water-soluble hormones lacking such modification. In addition, some water-soluble hormones also attach to binding proteins and therefore circulate in the blood longer than free water-soluble hormones CONTROL OF HORMONE SECRETION Three types of stimuli regulate hormone release: humoral, neural, and hormonal. Stimulation of Hormone Release Control by Humoral Stimuli - Blood-borne chemicals that directly stimulate the release of some hormones; - Sensitive to blood levels of a particular substance, such as glucose, calcium, or sodium. - When blood level of a particular chemical changes (calcium), the hormone (PTH) is released in response to the chemical’s concentration - Similarly, elevated blood glucose levels directly stimulate insulin secretion by the pancreas, and elevated blood potassium levels directly stimulate aldosterone release by the adrenal cortex Control by Neural Stimuli - Neurons release a neurotransmitter into the synapse with the cells that produce the hormone; - For instance, the sympathetic nervous system stimulates the secretion of epinephrine and norepinephrine, from the adrenal gland during exercise. Epinephrine and norepinephrine increase heart rate, in turn, increase blood flow through the exercising muscles. When the exercise stops, the neural stimulation declines and the secretion of epinephrine and norepinephrine decreases. - Some neurons secrete chemical messengers directly into the blood when stimulated, making the messengers, which are called neuropeptides. - Specialized neuropeptides stimulate hormone secretion from other endocrine cells and are called releasing hormones, a term usually reserved for hormones from the hypothalamus Inhibition of Hormone Release Although the stimulus of hormone secretion is important, inhibition is equally important 1. Humoral substances can inhibit the secretion of hormones; 2. Neural stimuli can prevent hormone secretion; 3. Inhibiting hormones prevent hormone release. Regulation of Hormone Levels in the Blood Two mechanisms: negative and positive feedback. 1. Negative Feedback - Most hormones are regulated by this, whereby the hormone’s secretion is inhibited by the hormone itself once blood levels have reached a certain point and there is adequate hormone to activate the target cell; - Ex. Thyroid hormones inhibit the secretion of their releasing hormone from the hypothalamus and their tropic hormone from the anterior pituitary. Control by Hormonal Stimuli - Occurs when a hormone is secreted that, in turn, stimulates the secretion of other hormones; - Most common hormones are from the anterior pituitary gland, called tropic hormones; - Tropic hormones: hormones that stimulate the secretion of another hormone; - The anterior pituitary tropic hormone then travels to another endocrine gland and stimulates the release of its hormones 2. Positive Feedback - Some hormones, when stimulated by a tropic hormone, promote the synthesis and secretion of the tropic hormone in addition to stimulating their target cell. In turn, this stimulates further secretion of the original hormone. Thus, it is self-propagating system; - Have rapid effects on target cells; most likely mediated through membrane-bound receptors 2. Water-soluble hormones bind to membrane-bound receptors - Polar and cannot pass through the cell membrane; - Instead, they interact with membrane-bound receptors, which are proteins that extend across the cell membrane, with their hormone-binding sites exposed on the cell membrane’s outer surface; - When a hormone binds to a receptor on the outside, the hormone-receptor complex initiates a response inside the cell; HORMONE RECEPTORS AND MECHANISMS OF ACTIONS Hormones exert their actions by binding to proteins called receptors. A hormone can stimulate only the cells that have the receptor for that hormone. Receptor site - portion of receptor molecule where a hormone binds; - the shape and chemical characteristics of each receptor site allow only a specific type of hormone to bind to it Specificity - the tendency for each type of hormone to bind to one type of receptor and not to others - Ex. Insulin binds to insulin receptors, but not to thyroid receptors - However, some hormones, such as epinephrine, can bind to a “family” of receptors that are structurally similar Action of Nuclear Receptors Lipid-soluble hormones stimulate protein synthesis. After, it diffuses across the cell membrane and bind to their receptors, the hormone-receptor complex binds to DNA to produce new proteins. The receptors that bind to the DNA have fingerlike projections that recognize and bind to specific nucleotide sequences in the DNA called hormone-response elements. The combination of the hormone and its receptor forms a transcription factor because, when the hormone-receptor complex binds to the hormone-response element, it regulates the transcription of specific messenger ribonucleic acid (mRNA) molecules. Hormone receptors have high affinity for the hormones that bind to them, only a small concentration of a given hormone is needed to activate a significant number of its receptors. Classes of Receptors Lipid-soluble and water-soluble hormones bind to their own classes of receptors. 1. Lipid soluble hormones bind to their nuclear receptors. - Small and are all nonpolar (freely cross a membrane) - Diffuse through the cell membrane and bind to nuclear receptors; - Nuclear receptors: can be located in the cytoplasm, but then move to the nucleus when activated Newly formed mRNA molecules move to the cytoplasm to be translated into specific proteins at the ribosomes. The new proteins produce the hormone’s effect at the target cell. Target cells that synthesize new protein molecules in response to hormonal stimuli normally a latent period of several hours between the time the hormones bind to their receptors and the time responses are observed. During this latent period, mRNA and new proteins are synthesized. Hormone-receptor complexes are eventually degraded within the cell, limiting the length of time hormones influence the cell’s activities, and the cells slowly return to their previous functional states. Membrane-Bound Receptors and Signal Amplification Receptors activate in two ways: (1) Some receptors alter the activity of G proteins at the inner surface of the cell membrane; (2) other receptors directly alter the activity of intracellular enzymes. Activation of G proteins, or intracellular enzymes, elicits specific responses in cells, including the production of molecules called second messengers. Second messenger: a molecule produced inside a cell once a ligand binds to its membrane-bound receptor. The second messenger then activates specific cellular processes inside the cell in response to the hormone. In some cases, this coordinated set of events is referred to as a second-messenger system. Example: cyclic adenosine monophosphate (cAMP) (the second messenger) is a common second messenger produced when a ligand binds to its receptor. Rather than the ligand (the first messenger) entering the cell to directly activate a cellular process, the ligand stimulates cAMP production. It is cAMP that then stimulates the cellular process. This mechanism is usually employed by water-soluble hormones that are unable to cross the target cell’s membrane. It has also been demonstrated that some lipid-soluble hormones activate second messenger systems which is consistent with actions via membrane-bound receptors. G Proteins That Interact with Adenylate Cyclase Activated α subunits of G proteins can alter the activity enzynes within the cell. For example, activated α subunits can influence the rate of cAMP formation by activating or inhibiting adenuylate cyclase, which is an enzyme that converts ATP to cAMP. Cyclic AMP functions as a second messenger. For example, cAMP binds to protein kinases and activates them. Protein kinases are enzymes that, in turn, regulate the activity of other enzymes. Depending on the other enzyme, protein kinases can increase or decrease its activity. The amount of time cAMP is present to produce a response in a cell is limited. An enzyme in the cytoplasm, called phosphodiesterase, breaks down cAMP to AMP. Once cAMP levels drop, the enzymes in the cell are no longer stimulated. Cyclic AMP can elicit many different responses in the body because each cell type possesses a unique set of enzymes. For example, the hormone glucagon binds to receptors on the surface of liver cells, activating G proteins and causing an increase in cAMP synthesis, which stimulates the activity of enzymes that break down glycogen into glucose for release from liver cells. Membrane-Bound Receptors that Activate G Proteins Many membrane-bound receptors produce responses through the action of G Proteins. Signal Amplification Nuclear receptors work by activating protein synthesis, which for some hormones can take several hours. However, hormones that stimulate the second messengers can produce an almost instantaneous response because the second messenger influences existing enzymes. In other words, the response proteins are already present. G Proteins - Consist of three subunits; from largest to smallest, they are called alpha (α), beta (ß), and gamma (γ). - Are so named because one of the subunits bind to guanine nucleotides. In the inactive state, the guanine diphosphate (GDP) molecule is bound to the α subunit of each G protein. In the active state, guanine triphosphate (GTP) is bound to the α subunit. After a hormone binds to a receptor on the outside, the receptor changes shape. As a result, the receptor binds to a G protein on the inner surface of the cell membrane, and GDP is released from the α subunit. Guanine triphosphate (GTP) binds to the α subunit, thereby activating it. The G proteins separate from the receptor, and the activated α separates from the ß and γ subunits. The activated α subunit can alter the activity of molecules within the cell membrane or inside the cell, thus producing cellular response. After a short time, the activated α subunit is turned off because the G protein removes a phosphate group from GTP, which converts it to GDP. Thus, the α subunit is called a GTPase. The α subunit then recombines with the ß and γ subunits. Additionally, each receptor produces thousands of second messengers, leading to a cascade effect and ultimately amplification of the hormonal signal. With amplification, a single hormone activates many second messengers, each of which activates enzymes that produce an enormous amount of final product. The efficiency of this second-messenger amplification is virtually unparalleled in the body and can be thought of as an “army of molecules” launching an offensive. One hormone could not single-handedly produce millions of final products within a few seconds. However, with amplification, one hormone has an army of molecules working simultaneously to produce the final products. Both nuclear receptor and membrane-bound receptor hormone systems are effective, but each is more suited to one type of response than another. For example, the reason epinephrine is effective in a fight-or-flight situation is that it can turn on the target cell responses within a few seconds. If running away from an immediate threat depended on producing new proteins, a process that can take several hours, many of us would have already perished. On the other hand, pregnancy maintenance is mediated by steroids, long-acting hormones, which are reflected by the fact that pregnancy is a long-term process. Thus, it is important that our bodies have hormones that can function over differing time scales. ENDOCRINE GLANDS AND THEIR HORMONES Endocrine system consists of ductless glands that secrete hormones into the interstitial fluid. The hormones then enter the blood. The organs in the body with the richest blood supply are endocrine glands, such as the adrenal gland and thyroid gland. Hormonal Control of the Anterior Pituitary The anterior pituitary synthesizes hormones, whose secretion is under the control of the hypothalamus. Neurons from the hypothalamus produce neuropeptides and secrete them into a capillary bed in the hypothalamus. The neuropeptides are then transported through veins to a second capillary bed in the anterior pituitary. Once the neuropeptides arrive at the anterior pituitary gland, they leave the blood and bind to membrane-bound receptors involved with regulating anterior pituitary hormone secretion. Pituitary and hypothalamus Pituitary gland (pituita = phlegm, thick mucus) - Also called the hypophysis; and considered as the master gland because it controls the function of so many other glands; - A small gland about the size of a pea; - Rests in a depression of the sphenoid bone inferior to the hypothalamus; lies posterior to the optic chiasm and connected to the hypothalamus by infundibulum - Hypothalamus: important autonomic nervous system and endocrine control center of the brain; - Two parts: ▪ Anterior pituitary – made up of epithelial cells derived from the embryonic oral cavity; ▪ Posterior pituitary – an extension of the brain and is composed of nerve cells; - Two ways the hypothalamus controls the gland: ▪ Hormonal control; and ▪ Direct innervation Hypothalamic-pituitary portal system - The capillary beds and veins that transport the releasing and inhibiting hormones The hypothalamic neuropeptides function as either releasing hormones or inhibiting hormones. Each releasing hormone stimulates the production and secretion of a specific hormone by the anterior pituitary, whereas such inhibiting hormone decreases the secretion of a specific anterior pituitary hormone. Direct Innervation of the Posterior Pituitary The posterior pituitary is a storage location for two hormones synthesized by special neurons in the hypothalamus. Stimulation of neurons within the hypothalamus controls the secretion of the posterior pituitary hormones. The cell bodies of these neurons are in the hypothalamus, and their axons extend through the infundibulum to the posterior pituitary. Hormones produced in the nerve cell bodies are transported through the axons to the posterior pituitary, where they are stored in the axon endings. When these nerve cells are stimulated, action potentials from the hypothalamus travel along the axons to the posterior pituitary and cause the release of hormones from the axon endings. Within the hypothalamus and pituitary, the nervous and endocrine systems are closely interrelated. Emotions such as joy and anger, as well as chronic stress, influence the endocrine system through the hypothalamus. Conversely, hormones of the endocrine system can influence the functions of the hypothalamus and other parts of the brain. Hormones of the Anterior Pituitary 1. Growth hormones (GH) - Stimulates growth of bones, muscles, and other organs by increasing gene expression; - Resists protein breakdown during periods of food deprivation and favors lipid breakdown; - Little growth may result from abnormal development of the pituitary gland; Pituitary dwarf - suffers from deficiency of growth hormone – remaining small, although normally proportioned; - treatment: administering growth hormone; Growth hormone is a protein – making it difficult to produce one artificially using conventional techniques, however, human genes of GH have been introduced into bacteria using genetic engineering techniques. The gene in the bacteria causes GH synthesis, and the GH can be extracted from the medium in which the bacteria are grown. Giantism - a condition in which a person who is abnormally tall - cause: excess of growth hormone secretion before bones finish growing in length and exaggerated bone growth results Acromegaly - facial features and hands are abnormally large - if excess hormone is secreted after growth in bone length is complete, growth continues in bone diameter only The secretion of growth hormone is controlled by two hormones from the hypothalamus – a releasing hormone stimulates growth hormone secretion, and an inhibiting hormone inhibits its secretion. In addition to growth hormone, genetics, nutrition and reproductive hormones influence growth. Insulin-like growth factors (IGFs) - - or somatomedins; a group of protein hormones that influences a portion of growth hormone growth hormone increases IGF secretion from tissues such as the liver, and the IGF molecules bind to receptors on the cells of tissues such as bone and cartilage where they stimulate growth. Similar in structure to insulin and can bind , to some degree, to insulin receptors Insulin, at high concentrations, can bind to IGF receptors 2. Thyroid-stimulating hormone (TSH) - Binds to membrane-bound receptors on cells of the thyroid gland and stimulates the secretion of thyroid hormone - Can also stimulate growth of the thyroid gland, thus when too much is secreted, the gland enlarges and secretes too much thyroid hormone; when too little is secreted, the gland decreases in size and secretes too little thyroid hormone; - Its secretion is regulated by a releasing hormone from the hypothalamus 3. Adrenocorticotropic hormone (ACTH) - Binds to membrane-bound receptors on adrenal cortex cells; - Increases the secretion of a hormone from the adrenal cortex called cortisol, also called hydrocortisone; - Required to keep the adrenal cortex from degenerating; - Its molecules bind to melanocytes in the skin and increase skin pigmentation; - Its secretion is increased by a releasing hormone from the hypothalamus; - Symptom of too much ACTH: darkening of the skin 4. Gonadotropins - Bind to membrane-bound receptors on the cells of the gonads (ovaries and testes) - Regulate the growth, development, and functions of the gonads - luteinizing hormone (LH) ▪ IN FEMALE: stimulates ovulation; it also promotes the secretion of the reproductive hormones, estrogen and progesterone from the ovaries; ▪ IN MALE: stimulates interstitial cells of the testes to secrete the reproductive hormone testosterone and thus sometimes is referred as interstitial cell-stimulating hormone (ICSH) - Follicle-stimulating hormone (FSH) ▪ IN FEMALE: stimulates development of follicles in ovaries; ▪ IN MALE: stimulates sperm cells in the testes - Without LH and FSH, the ovaries and testes decrease in size, no longer produce oocytes or sperm cells, and no longer secrete hormones; - A single releasing hormone from the hypothalamus increases the secretion of both LH and FSH; 5. Prolactin - Binds to membrane-bound receptors in cells of breast, where it helps promote development of the breast during pregnancy and stimulates the production of milk following pregnancy; - Regulation is complex and may involve several substance released from the hypothalamus - Two main regulatory hormones: one increases prolactin and one decreases it. 6. Melanocyte-stimulating hormone (MSH) - - Binds to membrane-bound receptors on melanocytes and causes them to synthesize melanin; Its structure is similar to that of ACTH, and oversecretion of either hormone causes the skin to darken; Its regulation is not well understood, but there appear to be two regulatory hormones from the hypothalamus – one that increases MSH secretion and one that decreases it - - Hormones of the Posterior Pituitary - - - Main function: secrete thyroid hormones; which bind to nuclear receptors in cells and regulate the rate of metabolism in the body; Synthesized and stores within the gland in numerous thyroid follicles Thyroid follicles: small spheres with walls composed of simple cuboidal epithelium; each is filled with protein thyroglobulin, to which thyroid hormones are attached ▪ Between each follicles is a network of loose connective tissue that contains capillaries and scattered parafollicular cells, or C cells, which secretes the hormone calcitonin Regulated by hormones from hypothalamus and pituitary: hypothalamus secretes TSH releasing hormone, also known as TRH. TRH travels to anterior pituitary to stimulate the secretion of TSH. In turn, TSH stimulates the secretion of thyroid hormones from the thyroid gland. Increasing blood levels of TSH = increase the synthesis and release of thyroid hormones from thyroglobulin; Decreasing blood levels of TSH = decrease the synthesis and release of thyroid hormones 1. Antidiuretic hormone (ADH) - Also called as vasopressin; - Binds to membrane-bound receptors and increases water reabsorption by kidney tubules, resulting in less water lost as urine; - Also cause blood vessels to constrict when released in large amounts - Reduced ADH release results in large amounts of dilute urine - Diabetes insipidus: lack of ADH secretion; the production of a large amount of dilute urine; condition is not obvious until the it become severe, producing many liters of urine each day ▪ The large urine volume is created by excess water loss from the blood, which increases the concentration of the body fluids and causes the loss of important electrolytes (Ca2+, Na+, and K+) ▪ Familiar to some who had alcohol to drink – the diuretic actions of the drink are due to its inhibition of ADH secretion 2. Oxytocin - Binds to membrane-bound receptors and causes contraction of the smooth muscle cells of the uterus as well as milk letdown from the breasts in lactating women (milk ejection) - Pitocin: commercial preparations of oxytocin; given under certain conditions to assist in childbirth and to constrict uterine blood vessels following childbirth THYROID GLAND - Made up of two lobes connected by a narrow band called isthmus; located on each side of the trachea, just inferior to the larynx - One of the largest endocrine glands; - Appears more red than the surrounding tissues because it is highly vascular; surrounded by a connective tissue capsule; The thyroid hormones have a negative-feedback effect on the hypothalamus and pituitary, so that increasing levels of thyroid hormones inhibit the secretion of TSH=releasing hormone from the hypothalamus and inhibit TSH secretion from the anterior pituitary gland. Decreasing thyroid hormone levels allow additional TSHreleasing hormone and TSH to be secreted. Because of negative feedback effect, the thyroid hormones fluctuate within a narrow concentration range in blood. A loss of negative feedback will result in excess TSH, causing the thyroid to enlarge, a condition called goiter. One type of goiter develops if iodine in the diet is too low. AS less thyroid hormone is synthesized and secreted, TSH-releasing hormone and TSH secretion increase above normal levels and cause dramatic enlargement of the thyroid gland. Thyroid hormones regulate growth and development. A lack of thyroid hormones is called hypothyroidism. In infants, it may result into cretinism. - Cretinism - Mental retardation, short stature, and abnormally formed skeletal structures; In adults, the lack of thyroid hormones results in a decreased metabolic rate. Individuals with hypothyroidism are extremely lethargic and have a hard time performing routine tasks. Myxedema - Also caused by hypothyroidism; - Accumulation of fluid and other molecules in the subcutaneous tissue of the skin Hyperthyroidism - Elevated rate of thyroid hormone secretion; - Causes an increased metabolic rate, extreme nervousness, and chronic fatigue Graves disease - an autoimmune disease that causes hyperthyroidism; - occurs when the immune system produces abnormal proteins that are similar in structure and function to TSH, which overstimulates the thyroid gland; - accompanied by bulging of the eyes, a condition called exophthalmia Thyroid gland requires iodine to synthesize two separate thyroid hormones. Iodine is taken up by the thyroid follicles and used to synthesize the thyroid hormones. Without iodine, thyroid hormones are neither produced nor secreted. Thyroid hormones: 1. Thyroxine or tetraiodothyronine - contains four iodine atoms and is abbreviated T4 2. Triiodothyronine - contains three iodine atoms and is abbreviated T3 Calcitonin - hormone secreted by the parafollicular cells of the thyroid gland; - secreted if the blood concentration of Ca2+ becomes too high; lowers blood Ca2+ levels to return to their normal range; - binds to membrane-bound receptors of osteoclasts and inhibits them; - a lack of calcitonin does not result in a prolonged increase in the levels By inhibiting of osteoclasts, it reduces the rate of Ca2+ reabsorption (breakdown) from bone. PARATHYROID GLANDS - four tiny glands are embedded in the posterior wall of the thyroid gland; - secretes hormone called parathyroid hormone (PTH), which is essential for the regulation of blood calcium levels; more important than calcitonin in regulating blood Ca2+ levels. Effects: ▪ PTH increases active Vit. D formation through effects on membrane-bound receptors of renal tubule cells in the kidneys. Vit. D stimulates increased Ca2+ absorption by intestinal epithelial cells; ▪ PTH secretion increases blood Ca2+ levels. PTH binds to receptors on osteoblasts. In turn, osteoblasts secrete substances that stimulate osteoclasts to reabsorb bone; ▪ PTH decreases loss of Ca2+ in the urine; Vitamin D is produced from precursors in the skin that are modified by the liver and kidneys. Ultraviolet light acting on the skin is required for the first stage of Vitamin D synthesis, and the final stage of synthesis in the kidney is stimulated by PTH. Vitamin D can also be supplied in the diet. Decreasing blood Ca2+ levels - Stimulate an increase in PTH secretion which also then increases rate of bone reabsorption. - Blood Ca2+ levels can be maintained within a normal range, but prolonged reabsorption of bone results in reduced bone density, as manifested by soft, flexible bones that are easily deformed in young people and porous, fragile bones in older people. - Nerves and muscles become excitable and produce spontaneous action potentials that cause frequent muscle cramps of tetanus; Increasing blood Ca2+ levels - Can cause a decrease in PTH secretion, which also then leads to a reduced blood Ca2+ levels. - In addition, increasing blood Ca2+ levels stimulate calcitonin secretion, which also causes blood Ca2+ levels to decline; - Make nerves and muscle cells less excitable, resulting in fatigue and muscle weakness Hyperparathyroidism - Abnormally high rate of PTH secretion; - Cause: tumor in a parathyroid gland; The excess Ca2+ can be deposited in soft tissues of the body, causing inflammation. In addition, kidney stones can result. Hypoparathyroidism - Abnormally low rate of PTH secretion; - Can result from injury to or the surgical removal of the thyroid and parathyroid glands; The low blood levels of PTH lead to reductions in the rate of bone reabsorption and the formation of vitamin D. The sympathetic nervous system is most active when a person is excited or physically active. Stress and low blood glucose levels can also cause increased sympathetic stimulation of the adrenal medulla. The epinephrine and norepinephrine are called the fight-or-flight hormones. Effects of the hormone released by the adrenal medulla: 1. Release of stored energy sources to support increased physical activity. These energy sources are glucose and fatty acids entering the blood. The glucose is primarily derived from breakdown of liver glycogen. The fatty acids are derived from the breakdown of adipose tissue. 2. Increased heart rate, which raises blood pressure. 3. Increased smooth muscle contraction in internal organ and skin blood vessels (called vasoconstriction), which also raises blood pressure. 4. Increased blood flow to skeletal muscle. The vasoconstriction in the internal organs and skin blood vessels reduces blood flow to those tissues. The smooth muscle in skeletal muscle blood vessels does not contract. That, in combination with decreased blood flow elsewhere, explains the increased blood flow to the skeletal muscle. 5. Increased metabolic rate of several tissues, especially skeletal muscle, cardiac muscle and nervous tissue. ADRENAL GLANDS - Two small glands superior to each kidney - Each gland has an inner part, called the adrenal medulla (marrow, or middle), and an outer part, called adrenal cortex (bark, or outer) - The adrenal medulla and the adrenal cortex function as separate endocrine glands; Adrenal Cortex - Secretes three classes of steroid hormones: mineralocorticoids, glucocorticoids, and androgens; all of which had target cells and binds to nuclear receptors; however, each class has unique structural and functional characteristics; ▪ Adrenal Medulla Epinephrine (adrenaline) - Principal hormone released from the adrenal medulla; Norepinephrine - Also released by the adrenal medulla Mineralocorticoids - helps regulate the blood volume and blood levels of K+ and Na+; - Aldosterone is the major hormone; primarily binds to receptor molecules in the kidney, but it also affects the intestine, sweat glands, and salivary glands; causes Na+ and water to be retained in the body and increases the rate of which K+ is eliminated (and also increased blood volume) - Adrenal gland is much more sensitive to changes in blood K+ levels than to changes in blood Na+ levels. - Elevated blood K+ levels and decreased blood Na+ levels each stimulate aldosterone secretion; Low blood pressure causes the release of a protein molecule called renin from the kidney. Renin, acts as an enzyme, and causes a blood protein called angiotensinogen to be converted to angiotensin I enzyme causes angiotensin I to be converted to angiotensin II. Angiotensin II - Causes smooth muscle in blood vessels to constrict, and acts on the adrenal cortex to increase aldosterone secretion. Activation of the sympathetic nervous system stimulates the adrenal medulla to secrete epinephrine and norepinephrine. Both blood vessels constriction and increased blood volume help raise blood pressure. ▪ ▪ Androgens - Secreted by the inner layer of the adrenal cortex - Stimulate the development of male secondary sex characteristics - Small amounts of androgens are secreted by the adrenal cortex both in male and females; - In adult males, most androgens are secreted by the testes; - In adult females, the adrenal androgens influence the female sex drive; - Secretion is abnormally high: exaggerated male characteristics develop un both male and females; most apparent in females and in males before puberty, when the effects are not masked by the secretion of androgens by the testes Glucocorticoids - Secreted by the middle layer of the adrenal cortex - Helps regulate blood nutrient levels - Cotisol: major hormone; Cortisol - increases the breakdown of proteins and lipids and increase their conversion to forms of energy the body can use; causes protein to be broken down to amino acids; - Example: cortisol causes the liver to convert amino acids to glucose, and it acts on adipose tissue, causing lipids to be broken down to fatty acids and released into the blood, taken up by tissues and used as a source of energy - In stressful condition, it is secreted in larger than normal amounts; thus it aids the body by providing energy sources for tissues; if stress is prolonged, the immune system can be suppressed enough to make the body susceptible to stress-related conditions Adrenocorticotropic hormone (ACTH) - Molecules from the anterior pituitary bind to membrane-bound receptors and regulate the secretion of cortisol from the adrenal cortex - Blood glucose decline = cortisol secretion increases; the low blood glucose acts on the hypothalamus to increase the secretion of the ACTH-releasing hormone, which in turn, stimulates cortisol secretion; - Without ACTH, the adrenal cortex atrophies and loses its ability to secrete cortisol PANCREAS, INSULIN AND DIABETES The endocrine part of the pancreas consists of pancreatic islets, which are dispersed throughout the exocrine portion of the pancreas. on target cells; the defective receptors do not respond normally to insulin In type 1 diabetes, tissues cannot take up glucose effectively, causing blood glucose levels to become very high, a condition called hyperglycemia. Because glucose cannot enter the cells of the satiety center in the brain without insulin, the satiety center responds as if there were very little blood glucose, resulting in an exaggerated appetite. The excess glucose in the blood is excreted in the urine, making the urine volume much greater than normal/. Because of excessive urine production, the person has a tendency to become dehydrated and thirsty. Even though blood glucose levels are high, lipids and proteins are broken down to provide an energy source for metabolism, resulting in the wasting away of body tissues, acidosis, and ketosis. Three parts of islets: 1. Alpha cells – secrete glucagon; 2. Beta cells – secretes insulin; and 3. Delta cells – secrete somatostatin All these hormones regulate the blood levels of nutrients, especially glucose, which is very important. A below normal blood glucose level causes the nervous system to malfunction because glucose is the nervous system’s main source of energy. The tissues also rapidly break down lipids and proteins to provide an alternative energy source. As these lipids are broken down, the liver converts some of the fatty acids to ketones, which are released into the blood. When blood glucose is very low, the breakdown of lipids can cause the release of enough fatty acids and ketones to reduce the pH of the body fluids below normal, a condition called acidosis. Elevated blood glucose levels stimulate beta cells to secrete insulin. Additionally, increased parasympathetic stimulation associated with digestion of a meal stimulates insulin secretion. Increased blood levels of certain amino acids also stimulate insulin secretion. Two signals that inhibit insulin secretion: low blood glucose levels and stimulation of the sympathetic nervous system. The decrease of insulin levels allows blood glucose to be conserved to provide the brain with adequate glucose and to allow other tissues to metabolize fatty acids and glycogen stored in the cells. Major target tissues for insulin: liver, adipose tissue, muscles, and the area of the hypothalamus that controls appetite, called satiety center. Insulin binds to membrane-bound receptors and either directly or indirectly, increases the rate of glucose and amino acid uptake in these tissues. Glucose is converted into glycogen or lipids, and the amino acids are used to synthesize protein. Diabetes mellitus - Body’s inability to regulate blood glucose levels within the normal range; - Two types: ▪ Type 1 – occurs when too little insulin is secreted from the pancreas ▪ Type 2 – caused by either too few insulin receptors on target cells or defective receptors People with this condition also exhibit a lack of energy. Insulin must be injected regularly to adequately control blood glucose levels. When too much insulin is present, as occurs when a diabetic is injected with too much insulin or has not eaten after an insulin injection, blood glucose levels become very low. The brain, which depends primarily on glucose for an energy source, malfunctions. This condition, called insulin shock, can cause deterioration and convulsions and may result in loss of consciousness. Fortunately, genetic engineering has allowed synthetic insulin to become widely available to diabetics. Glucagon - Released from the alpha cells when blood glucose levels are low; - Binds to membrane-bound receptors primarily in the liver, causing the glycogen stored in the liver to be converted to glucose; it is the released into the blood glucose levels; after a meal, when blood glucose levels are elevated, glucagon secretion is reduced. Somatostatin - Released by the delta cells in response to food intake; - Inhibits the secretion of insulin and glucagon and inhibits gastric tract activity; - Small, pinecone-shaped structure located superior and posterior to the thalamus of the brain; Produces a hormone called melatonin; Melatonin: thought to inhibit the reproductive hypothalamic-releasing hormone, gonadotropinreleasing hormone; By inhibiting the hypothalamic-releasing hormone, it prevents its secretion of reproductive tropic hormones, LH and FSH from the anterior pituitary. Thus, melatonin inhibits the reproductive system. Insulin and glucagon together regulates glucose levels. When blood glucose levels increases = insulin secretion increases, and glucagon secretion decreases. When blood glucose levels decreases = the rate of insulin secretion decreases, and the rate of glucagon secretion increases. Hormones such as epinephrine, cortisol, and growth hormone maintain blood levels of nutrients. When blood glucose levels decreases = these hormones are secreted at a greater rate. Epinephrine and cortisol cause the breakdown of protein and lipids and the synthesis of glucose to help increase blood levels of nutrients. Growth hormone slows protein breakdown and favors lipid breakdown. TESTES AND OVARIES In addition to producing sperm cells and egg cells, the testes and ovaries also secrete reproductive hormones. These hormones are important in the development of sexual characteristics. Structural and functional differences between two genders, as well as the ability to reproduce, depend on the reproductive hormones. Testosterone - Main reproductive hormone in males; - Secreted by the testes; - Responsible for the growth and development of the male reproductive structures, muscle enlargement, the growth of body hair, voice changes, and the male sexual drive In females, there are two main classes of RH: estrogen and progesterone – both secreted by the ovaries. Together, they contribute to the development and function of female reproductive structure and female characteristics, such as enlargement of the breasts and the distribution of adipose tissue – which influences the shape of the hips, breasts, and thighs. In addition, the female menstrual cycle is controlled by the cylical release of estrogen and progesterone from the ovaries. LH and FSH stimulate the secretion of hormones from the ovaries and testes. Releasing hormones from the hypothalamus controls the rate of LH and FSH. In turn, LH and FSH control the secretion of hormones from the ovaries and testes. Hormones secreted by the ovaries and testes have a negativefeedback effect pm the hypothalamus and anterior pituitary. THYMUS - Lies in the upper part of the thoracic cavity; - Important in the function of the immune system; - Secretes a hormone called thymosin, which aids the development of white blood cells called T cells; - T cells: protect the body against infection by foreign organisms; - Most important early in life; if an infant is born without a thymus, the immune system does not develop normally, and the body is less capable of fighting infections PINEAL GLAND Amount of available light always plays a part in the rate of melatonin secretion. Short day length = decrease in melatonin; longer day length = increase in melatonin. It also plays a part in the onset of puberty in humans. Tumors may develop in the pineal gland, which increase pineal secretions in some cases but decrease them in others. OTHER HORMONES Cells in the lining of the stomach and small intestine secrete hormones that stimulate the production of digestive juices from the stomach, pancreas, and liver. This secretion occurs when food is present in the digestive system, but not at other times. Hormones secreted from the small intestine also help regulate the rate at which food passes from the stomach into the small intestine. Prostaglandins are widely distributed in tissues of the body, where they function as intercellular signals. Unlike most hormones, they are usually not transported long distances in the blood but function mainly as autocrine or paracrine chemical signals. Thus, their effects occur in the tissues where they are produced. Some prostaglandins cause relaxation of smooth muscle, such as dilation of blood vessels. Others cause contraction of smooth muscle, such as contraction of the uterus during the delivery of a baby. Because of their actions on the uterus. Prostaglandins have been used medically to initiate abortion. Prostaglandins also play a role in inflammation. They are released by damaged tissues and cause blood vessel dilation, localized swelling, and pain. Prostaglandins produced by platelets appear to be necessary for normal blood clotting. The ability of the aspirin and related substances to reduce pain and inflammation, to help prevent the pain cramping of uterine smooth muscle, and to treat headache as a result of their inhibitory effect on prostaglandins synthesis. The right atrium of the heart secretes atrial natriuretic hormone (ANH, also called ANP), in response to elevated blood pressure. ANH inhibits Na+ reabsorption in the kidneys. This causes more urine to be produced, reducing blood volume. Lowered blood volume, lowers blood pressure. The kidneys secrete the hormone erythropoietin in response to reduced oxygen levels in the kidney. Erythropoietin acts on bone marrow to increase the production of red blood cells. In pregnant women, the placenta is an important source hormone that maintains pregnancy and stimulates breast development. These hormones are estrogen, progesterone, and human chorionic gonadotropin, which is similar in structure and function to LH. EFFECTS OF AGING ON ENDOCRINE SYSTEM Age related changes to the endocrine system include a gradual decrease in the secretion of some, but not all, endocrine glands. Some of the decreases in secretion may be due to the fact that older people commonly engage in less physical activity. GH secretion decreases as people age. However, regular exercise offsets this decline. Older people who do not exercise have significantly lower GH levels than older people who exercise regularly. Decreasing GH levels may explain the gradual decrease in bone and muscle mass and the increase in adipose tissue seen in many elderly people. So far, administering GH to slow or prevent the consequences of aging has not been found to be effective, and unwanted side effects are possible. A decrease in melatonin secretion may influence age-related changes in sleep patterns, as well as the decreased secretion of some hormones, such as GH and testosterone. The secretion of thyroid hormones decreases slightly with age. Age-related damage to the thyroid gland by the immune system can occur. Approximately 10% of elderly women experience some reduction in thyroid hormone secretion; this tendency is less common in men. The kidneys of the elderly secrete less renin, reducing the ability to respond to decreases in blood pressure. Reproductive hormone secretion gradually declines in elderly men, and women experience menopause. Secretion of thymosin from the thymus decreases with age. Fewer functional lymphocytes are produced, and the immune system becomes less effective in protecting the body against infections and cancer. Parathyroid hormone secretion increases to maintain blood calcium levels if dietary Ca2+ and vitamin D levels decrease, as they often do in the elderly. Consequently, a substantial decrease in bone matrix may occur. In most people, the ability to regulate blood glucose does not decrease with age. However, there is an age-related tendency to develop type 2 diabetes mellitus for those who have a familial tendency, and it is correlated with age-related increases in body weight.
