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pnu.edu.sa OCC103 Human Structure & Function 1 Endocrine System Week 13 Lecture 1 Certain images and/or photos on this page are the copyrighted property of 123RF Limited, their Contributors or Licensed Partners and are being used with permission under license. These images and/or photos may not be copied or downloaded without permission from 123RF Limited. Endocrine System: Overview • acts with the nervous system to coordinate and integrate the activity of body cells ⟶ Influences metabolic activities by means of hormones transported in the blood ⟶ Responses occur more slowly but tend to last longer than those of the nervous system Learning outcome 1 Define the term ‘endocrine gland’ and state the locations of the major endocrine glands endocrine glands Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands The hypothalamus has both neural and endocrine functions Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Other tissues that produce hormones include adipose cells, cells in the walls of the small intestine, stomach, kidneys, and heart • Functions under hormonal control The major processes coordinated by hormones include: ⟶ growth and development ⟶ reproduction ⟶ maintenance of components of blood: erythrocytes, water, electrolytes, nutrients ⟶ energy utilization, including the determination of metabolic rate ⟶ mobilization of body defences including stress responses All of these processes involve the coordination of many physiological activities over long periods of time. Chemical messengers • Hormones: long-distance chemical signals that travel in the blood or lymph to target cells • Other hormone-like chemicals act locally on nearby cells and will not be considered part of the endocrine system e.g. cytokines produced by the immune system Target cells must have specific receptors to which the hormone binds Cells are activated by hormones binding to receptors Target Cell Activation • Target cell activation depends on three factors 1. Blood levels of the hormone 2. Relative number of receptors on or in the target cell 3. Affinity of binding between receptor and hormone • Hormones influence the number of their receptors ⟶ Up-regulation—target cells form more receptors in response to the hormone ⟶ Down-regulation—target cells lose receptors in response to the hormone e.g. type 2 diabetes Learning outcome 2 Distinguish between water-soluble hormones which bind to cell membranes and lipidsoluble hormones which pass through cell membranes to interact with DNA hormone s Certain images and/or photos on this page are the copyrighted property of 123RF Limited, their Contributors or Licensed Partners and are being used with permission under license. These images and/or photos may not be copied or downloaded without permission from 123RF Limited. Chemistry of hormones Two main classes: 1. Amino acid-based hormones ⟶ Amines, thyroxine, peptides, and proteins 2. Steroid hormones ⟶ Synthesized from cholesterol in the testes/ovaries and adrenal gland Amino-acid image attributed to http://catalog.flatworldknowledge.com/ Steroid image attributed to McGraw-Hill Companies Ltd Amino acid-based hormones Water-soluble hormones (all amino acid–based hormones except thyroid hormone) • Cannot enter the target cells • Act on plasma membrane receptors • Coupled by G proteins to intracellular second messengers that mediate the target cell’s response • Activate or deactivate enzyme systems http://www.youtube.com/watch?v=tMMrTRnFdI4&feature=related Example: Glucagon Receptor activates G protein G protein activates adenylate cyclase cAMP acts as a 2nd messenger Steroid hormones and thyroid hormone Lipid-soluble hormones 1. Diffuse into their target cells and bind with intracellular receptors 2. Receptor-hormone complex enters the nucleus 3. Directly activate genes to make proteins Example: Cortisol http://www.youtube.com/watch?v=oOj04WsU9ko&NR=1 Steroid hormone Extracellular fluid Cytoplasm Receptor protein Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds to an intracellular receptor. Receptorhormone complex Nucleus Figure 16.3, step 1 Steroid hormone Extracellular fluid Cytoplasm Receptor protein Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Receptorhormone complex 2 The receptor- Nucleus hormone complex enters the nucleus. Figure 16.3, step 2 Steroid hormone Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Receptorhormone complex Cytoplasm Receptor protein 2 The receptor- Nucleus Hormone response elements DNA hormone complex enters the nucleus. 3 The receptor- hormone complex binds a hormone response element (a specific DNA sequence). Figure 16.3, step 3 Steroid hormone Extracellular fluid Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Receptorhormone complex Cytoplasm Receptor protein 2 The receptor- Nucleus Hormone response elements DNA mRNA hormone complex enters the nucleus. 3 The receptor- hormone complex binds a hormone response element (a specific DNA sequence). 4 Binding initiates transcription of the gene to mRNA. Figure 16.3, step 4 Steroid hormone Plasma membrane Extracellular fluid 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Cytoplasm Receptor protein Receptorhormone complex 2 The receptor- Nucleus Hormone response elements DNA mRNA hormone complex enters the nucleus. 3 The receptor- hormone complex binds a hormone response element (a specific DNA sequence). 4 Binding initiates transcription of the gene to mRNA. 5 The mRNA directs New protein protein synthesis. Figure 16.3, step 5 Hormone transport in blood • Hormones circulate in the blood either free or bound ⟶ Steroids and thyroid hormone are attached to plasma proteins ⟶ All others circulate without carriers • The concentration of a circulating hormone depends on the: ⟶ rate of release from endocrine glands ⟶ speed of inactivation and removal from the body by metabolism in the liver and excretion by the kidneys Control of hormone release • Blood levels of hormones ⟶ Are controlled by negative feedback systems ⟶ Vary only within a narrow desirable range • Three factors stimulate release of hormones: (a) Humoral Stimulus 1 Capillary blood contains low concentration of Ca2+, 1. Blood levels of ions/nutrients stimulate hormone release Example: Ca2+ ions in the blood Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete parathyroid hormone (PTH) which stimulates… Capillary (low Ca2+ in blood) Parathyroid glands Thyroid gland (posterior view) PTH 2 Parathyroid glands …secretion of parathyroid hormone (PTH) by parathyroid glands* PTH causes Ca2+ concentrations to rise and the stimulus is removed Figure 16.4a (b) Neural Stimulus 1 Preganglionic sympathetic fibers stimulate adrenal 2. Nerves stimulate hormone release Sympathetic nervous system fibers stimulate the adrenal medulla to secrete epinephrine and norepinephrine medulla cells… CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary 2 …to secrete catecholamines (epinephrine and norepinephrine) Figure 16.4b (c) Hormonal Stimulus 1 The hypothalamus secretes hormones that… 3. Hormones stimulate other endocrine organs to release their hormones Hypothalamus 2 …stimulate the anterior pituitary gland to secrete Pituitary hormones gland that… Thyroid Adrenal Gonad gland cortex (Testis) 3 …stimulate other endocrine http://www.youtube.com/watch?v=hLeBNyB1qKU glands to secrete hormones Figure 16.4c Nervous System Modulation • The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms For example: under severe stress, the hypothalamus and the sympathetic nervous system are activated ⟶ As a result, body glucose levels rise Learning outcome 3 Describe the structure of the pituitary gland and its vascular and neural relationships to the hypothalamus Certain images and/or photos on this page are the copyrighted property of 123RF Limited, their Contributors or Licensed Partners and are being used with permission under license. These images and/or photos may not be copied or downloaded without permission from 123RF Limited. The Pituitary Gland and Hypothalamus • The pituitary gland (hypophysis) is located at the base of the brain, immediately below the hypothalamus. It is connected to the hypothalamus by a pituitary stalk Pituitary-Hypothalamic relationships • The pituitary gland comprises 2 lobes: posterior (neurohypophysis) and anterior (adenohypophysis) • The posterior pituitary is an extension of the hypothalamus, and consists of neural tissue – The hormones are synthesised in the hypothalamus neurons. – They are transported down the axons and stored in vesicles in the axon ending located in the posterior pituitary – Nerve impulses travel down axons into the posterior pituitary. – This causes the release of the vesicles of hormones into the blood stream at the posterior pituitary Pituitary-Hypothalamic relationships • The anterior pituitary has no direct neural connection to the brain. ⟶ Blood from the hypothalamus drains into capillaries of the anterior pituitary ⟶ releasing and releaseinhibiting hormones are carried in the blood to the anterior pituitary to regulate hormone release Learning outcome 4 List the hormones secreted by the pituitary gland, the major actions and the consequences of hyposecretion and hypersecretion Certain images and/or photos on this page are the copyrighted property of 123RF Limited, their Contributors or Licensed Partners and are being used with permission under license. These images and/or photos may not be copied or downloaded without permission from 123RF Limited. Hormone Secretion Posterior Pituitary hormones • The posterior pituitary secretes two peptide hormones: ⟶ oxytocin (OT) ⟶ antidiuretic hormone (ADH); also known as vasopressin Oxytocin • Stimulates uterine contractions during childbirth by mobilizing Ca2+ through a second-messenger system • Also triggers milk ejection (“letdown” reflex) in women producing milk • Plays a role in sexual function in males and females Certain images and/or photos on this page are the copyrighted property of 123RF Limited, their Contributors or Licensed Partners and are being used with permission under license. These images and/or photos may not be copied or downloaded without permission from 123RF Limited. Antidiuretic Hormone (ADH) • Osmoreceptors in the hypothalamus respond to changes in the solute concentration of the blood plasma • If solute concentration is high ⟶ Osmoreceptors depolarize and transmit impulses to hypothalamic neurons ⟶ ADH is synthesized and released, inhibiting urine formation by the kidneys • Anterior Pituitary hormones All are proteins • All except GH activate cyclic AMP second-messenger systems at their targets • TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands) Growth Hormone (GH) • Stimulates cell division targets bone and skeletal muscle • Promotes protein synthesis and encourages use of fats for fuel • Most effects are mediated indirectly by insulin-like growth factors (IGFs) http://www.youtube.com/watch?v=hLeBNyB1qKU Thyroid-Stimulating Hormone • Produced by the anterior pituitary • Stimulates the normal development and secretory activity of the thyroid • Regulation of TSH release ⟶ Stimulated by thyrotropin-releasing hormone (TRH) ⟶ Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus Adrenocorticotropic Hormone (ACTH) • Secreted by the anterior pituitary • Stimulates the adrenal cortex to release cortisol and aldosterone (to a lesser extent) • Regulation of ACTH release ⟶ triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm ⟶ internal and external factors such as fever, hypoglycaemia, and stressors can alter the release of CRH Gonadotropins • Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secreted by the anterior pituitary ⟶ FSH stimulates gamete (egg or sperm) production ⟶ LH promotes production of gonadal hormones Prolactin (PRL) • Secreted by the anterior pituitary • Stimulates milk production • Regulation of PRL release – Primarily controlled by prolactininhibiting hormone (PIH) (dopamine) • Blood levels rise toward the end of pregnancy • Suckling stimulates PRH release and promotes continued milk production Learning outcome 5 Describe the major actions of the following hormones: ⟶ thyroid hormone ⟶ parathyroid hormone ⟶ insulin, glucagon ⟶ cortisol ⟶ aldosterone ⟶ adrenalin (epinephrine) ⟶ erythropoietin 7 hormone s Certain images and/or photos on this page are the copyrighted property of 123RF Limited, their Contributors or Licensed Partners and are being used with permission under license. These images and/or photos may not be copied or downloaded without permission from 123RF Limited. Thyroid Gland • This gland is located at the front of the neck, below the larynx. • Follicular cells secrete thyroxine (T4) and triiodothyronine (T3), collectively termed “thyroid hormone” (TH) • Other Thyroid cells produce a second hormone “calcitonin” Thyroid Hormone • Major metabolic hormone • The effects of TH are: ⟶ stimulation of growth (in conjunction with growth hormone) ⟶ development of the nervous system in the foetus and infant ⟶ increased basal metabolic rate and increased heat production ⟶ increased alertness, reflexes TH is derived from the amino acid tyrosine, and iodine (I) Hypothalamus Thyroid Hormone TRH Anterior pituitary TSH Negative feedback regulation of TH release Rising TH levels provide negative feedback inhibition on release of TSH Thyroid gland Thyroid hormones Target cells Stimulates Inhibits Calcitonin • Produced by parafollicular cells of the thyroid gland • Antagonist to parathyroid hormone (PTH) • Inhibits osteoclast activity and release of Ca2+ from bone matrix • Stimulates Ca2+ uptake and incorporation into bone matrix Parathyroid Glands • Four to eight tiny glands embedded in the posterior aspect of the thyroid gland • secrete parathyroid hormone (PTH), a peptide hormone • PTH—most important hormone in Ca2+ homeostasis • Functions ⟶ Stimulates osteoclasts to digest bone matrix ⟶ Enhances reabsorption of Ca2+ and secretion of phosphate by the kidneys ⟶ Promotes activation of vitamin D (by the kidneys); increases absorption of Ca2+ by intestinal mucosa Adrenal Glands • Paired, pyramid-shaped organs atop the kidneys • Structurally and functionally, they are two glands in one – Adrenal medulla —nervous tissue; part of the sympathetic nervous system – Adrenal cortex —three layers of glandular tissue that synthesize and secrete corticosteroids Adrenal Glands The cortex secretes corticosteroids (aldosterone and cortisol) and androgens (male sex hormones) The medulla secretes catecholamines (adrenalin, noradrenalin) Mineralocorticoids • Mineralocorticoids regulate electrolytes (primarily Na+ and K+) in ECF ⟶ Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions ⟶ Importance of K+: sets resting membrane potential of cells • Aldosterone is the most potent mineralocorticoid (a steroid) ⟶ Stimulates Na+ reabsorption and water retention by the kidneys Glucocorticoids (Cortisol) • Keep blood sugar levels relatively constant • Maintain blood pressure by increasing the action of vasoconstrictors • Cortisol is the most significant glucocorticoid ⟶ Released in response to ACTH, patterns of eating and activity, and stress ⟶ Prime metabolic effect is gluconeogenesis - formation of glucose from fats and proteins ⟶ Promotes rises in blood glucose, fatty acids, and amino acids Aldosterone (i) • Aldosterone regulates Na+ and K+ in blood and other extracellular fluids (ECF) – Importance of Na+: affects water content of ECF thus affects blood volume, blood pressure, blood concentrations of other solutes – Importance of K+: sets resting membrane potential of cells Aldosterone (ii) Aldosterone acts at the kidney tubule to – Stimulate Na+ reabsorption and water retention by the kidneys – Stimulate K+ secretion in kidney tubules and thus its removal from the blood Aldosterone secretion is increased by: • falling blood pressure: thus Na+ is reabsorbed, water is passively reabsorbed with it, and blood volume is maintained • rising blood levels of K+ : excess K+ is secreted from the blood, leaves the body in urine, and levels do not rise to adversely affect excitable tissue such as nerve, cardiac muscle Gonadocorticoids (Sex Hormones) • Most are androgens (male sex hormones) that are converted to testosterone in tissue cells or estrogens in females • May contribute to ⟶ The onset of puberty ⟶ The appearance of secondary sex characteristics ⟶ Sex drive http://www.youtube.com/watch?v=V08dWz5XNBA&feature=related Adrenal Medulla • cells in the adrenal medulla secrete adrenalin (80%) and noradrenalin (20%) • These hormones cause ⟶ Blood glucose levels to rise ⟶ Blood vessels to constrict ⟶ The heart to beat faster ⟶ Blood to be diverted to the brain, heart, and skeletal muscle Stress Pancreas • Has both exocrine and endocrine cells ⟶ Exocrine produce an pancreatic juice for digestion ⟶ Pancreatic islets (islets of Langerhans) contain endocrine cells: ⇉ Alpha () cells produce glucagon ⇉ Beta () cells produce insulin Blood glucose regulation Glucagon raises blood glucose Major target is the liver, where it promotes: • Glycogenolysis: breakdown of glycogen to glucose • Gluconeogenesis: synthesis of glucose from amino acids and fatty acids • Release of glucose to the blood Insulin lowers blood glucose Effects of insulin • Lowers blood glucose levels • Enhances membrane transport of glucose into fat and muscle cells • Activates an enzyme cascade which leads to: ⟶the oxidation of glucose for ATP production ⟶ Polymerize glucose to form glycogen ⟶ Convert glucose to fat (particularly in adipose tissue) Stimulates glucose uptake by cells Tissue cells Insulin Stimulates Pancreas glycogen formation Glucose Blood Glycogen Liver glucose falls to normal range. Stimulus Blood glucose level Stimulus Blood Blood glucose level glucose rises to normal range. Glucose Pancreas Liver Glycogen Stimulates glycogen breakdown Glucagon Figure 16.18 • Other hormone-producing tissues Kidneys – Erythropoietin stimulates production of red blood cells • Adipose tissue (fat tissue) – Leptin is involved in appetite control, and stimulates increased energy expenditure • Stomach, small intestine – Hormones that regulate metabolic and digestive functions • Heart – Hormone that helps regulate blood volume, blood pressure