Homeostasis and Hormonal Control PDF

Homeostasis and Hormonal control Dr M. Ellul 5.1 Homeostasis 5.1.1. Concept of Homeostasis Syllabus: Maintenance and control of internal environment 1 Homeostasis and Hormonal...

Homeostasis and Hormonal control Dr M. Ellul 5.1 Homeostasis 5.1.1. Concept of Homeostasis Syllabus: Maintenance and control of internal environment 1 Homeostasis and Hormonal control Dr M. Ellul Homeostasis An organism may be defined as a physico-chemical system existing in a steady state with its external environment. The external environment is the environment in which the organisms live, and the internal environment is the environment in which the individual cells live. Homeostasis is the maintenance of constant conditions in the internal environment. (Source: Life: the Science of Biology) The body maintains a steady state of temperature, glucose, carbon dioxide, nitrogenous wastes (urea) etc. Homeostatic mechanisms Homeostatic mechanisms make organisms independent of the environment, (which is changing continuously.) Homeostatic mechanisms can be:  Anatomical e.g. thick fat layer to prevent heat loss.  Physiological e.g. secretion of thyroxine to raise the basal metabolic rate (B.M.R.)  Behavioural e.g. seeking shade to avoid heat gain. 2 Homeostasis and Hormonal control Dr M. Ellul 5.1 Homeostasis 5.1.2. Physiological regulation Syllabus: Control systems and the concept of negative feedback. Example of a control system. (Recall concept of positive feedback in menstrual cycle and parturition Section 9.5) 3 Homeostasis and Hormonal control Dr M. Ellul Control systems What is stress? Any condition that tends to upset the smooth operation of a system, e.g. a high blood glucose level. Stresses can be internal or external. Internal stresses are caused by the processes of life, e.g. concentration changes in carbon dioxide, nitrogenous wastes, heat. External stresses are environmental processes e.g. temperature, enemies, lack of food, decreasing length of day. Living systems are now seen as open systems, that is, they require a continuous exchange of matter between the environment and themselves. For homeostasis to take place there must be a detector to recognise stress. Also there must be effectors (or rectifiers) to normalise the situation. In order to achieve homeostasis, organisms make use of control systems. The basic components of a control system include: REGULATOR Input Detector Effector Output Set point responce body CHANGE RECEPTOR CONTROL responce CENTER  Input: a change in the environment that can be detected by an organism.  Detector (receptor): detects a change in some variable of the animal’s internal environment. thermoreceptors  Regulator (control centre): processes information it receives from the detector. It 37 % compares the information with the set point. Detects high temp (Hypothalemus).  Set point (reference point): the desired value, amount or concentration (Optimum level).  Effector: brings about an appropriate response according to the detected change.  Output: the actual response observed in the body i.e. a physiological or behavioural change. The more efficient the control system is:  Less change there is from the reference point.  The faster the system responds to the change. 4 Homeostasis and Hormonal control Dr M. Ellul (Source: Life: the Science of Biology) The function of feedforward feedback is to change the set point. Seeing a deer changes the set point by slowing down. Feedback Feedback refers to the interdependence of input and output into the system that is there should be feedback information between the detector and the effector. Feedback can be positive or negative. Negative feedback is when an increase of one substance causes a decrease of another substance. Positive feedback is when an increase of one substance causes an increase of another substance. Negative feedback In negative feedback, a change in the internal environment leads to a response, which counteracts further change in the same direction. Therefore, the response restores the system to its original state. 5 Homeostasis and Hormonal control Dr M. Ellul The majority of homeostatic control mechanisms in organisms use negative feedback to maintain homeostatic balance (ie. to keep certain physiological factors, such as blood glucose concentration, within certain limits) Negative feedback control loops involve:  A receptor (or sensor) which detects a stimulus that is involved with a condition / physiological factor.  A coordination system (nervous system and endocrine system) which transfers information between different parts of the body.  An effector (muscles and glands) which carries out a response. Outcome of a negative feedback loop: The factor/stimulus must be continuously monitored.  If there is an increase in the factor, the body responds to make the factor decrease.  If there is a decrease in the factor, the body responds to make the factor increase. The system is restored to its original level. 6 Homeostasis and Hormonal control Dr M. Ellul Thermoregulation is an example of negative feedback: Thyroxine is a hormone released by the thyroid gland, which regulates the basal metabolic rate, growth and development of an organism. Control of thyroxine release by the thyroid gland is another example of negative feedback. In this example, the detector is the hypothalamus, the regulator is the pituitary gland and the effector is the thyroid gland. 7 Examples of negative feedback Homeostasis and Hormonal control Dr M. Ellul The hypothalamus monitors the concentration of thyroxine in blood. A low concentration stimulates the release of TRF (thyroid releasing factor) by the hypothalamus. This causes the release of TSH (thyroid stimulating hormone) released from the anterior pituitary gland. TSH brings about the release of thyroxine from the thyroid gland. When the concentration of thyroxine is restored, then negative feedback prevents further release of the hormone of the hormone. Positive Feedback In positive feedback, a change produces a response that intensifies the original change. Therefore, a disturbance leads to events that amplify (increase) the disturbance even further. This response leads the system to an extreme state. An example of positive feedback occurs during childbirth. Oxytocin (secreted in the pituitary gland) stimulates contractions of the muscles in the myometrium. Oxytocin is released by the pituitary gland in the brain. Stretch receptors in the cervix detect the contractions and signal the pituitary gland to increase oxytocin secretion. More oxytocin creates further contractions, which in turn signal for further release of oxytocin in this positive feedback loop. This process increases the contractions slowly and rhythmically. The process leads to the singular event of childbirth. 8 Homeostasis and Hormonal control Dr M. Ellul Another example of positive feedback occurs during the menstrual cycle during the days leading to ovulation. During most of the menstrual cycle, oestrogen and progesterone provide negative feedback to the hypothalamus and pituitary gland. This keeps their levels more or less constant. During days 12–14, however, oestrogen provides positive feedback to the hypothalamus and pituitary gland. This causes a rapid rise in the production of oestrogen by the ovaries and leads to ovulation. - By increasing the levels of luteising hormone (LH) Self-assessment: For each of the following feedback loops, determine if it is positive or negative: 1. Clotting: An enzyme is produced that forms the matrix of the blood clot, but also speeds up the production of that same enzyme. _____________________ 2. Oxygen levels: When the kidneys sense low oxygen levels in the blood, they send hormonal signals to bone marrow to make more red blood cells. _______________________ 3. Childbirth: Stretching of the uterus triggers secretions of a contraction-stimulating hormone to speed up labour. ____________________ 4. Temperature regulation: When blood temperature drops, signals are sent to contract the arteries near the skin and to begin shivering. These serve to keep blood in the core and to release heat energy. ___________________ 5. Glucose levels: When blood glucose levels fall, insulin secretion is inhibited and glucose synthesis is stimulated. ______________________ Control of Homeostatic Mechanisms A system must be capable of detecting disturbances both internally and externally. The system must communicate the information to other parts of the body. There are 2 ways by which homeostasis is achieved: The nervous system coordinates rapid and precise responses to stimuli using action potentials. The endocrine system maintains homeostasis and long-term control using chemical signals. The endocrine system works in parallel with the nervous system to control growth and maturation along with homeostasis. 9 Homeostasis and Hormonal control Dr M. Ellul Nervous control Hormonal control Fast responses Slower responses Impulses pass along Neurons Hormones carried by the blood Responses precise and localised Responses diffuse and widespread Rapid, short-lived responses Slower responses which continue over a long period Both systems make use of chemical transmitters In fact, several physiological processes involve structural and functional overlap between the endocrine and nervous system. Eg. Noradrenaline (also known as norepinephrine) is a neurotransmitter (involved in the nervous system) is similar in structure to adrenaline (also known as epinephrine) which is a hormone released by the adrenal medulla (centre of the adrenal gland). They are released together and thus reinforce the effects of each other e.g. inhibit peristalsis and digestion, increase blood pressure, increase mental awareness etc. [Note: They differ in their effect on blood vessels:  Noradrenaline causes vasoconstriction of all blood vessels.  Adrenaline causes vasoconstriction of blood vessels supplying skin and gut, and vasodilation of bloods vessel supplying muscles and brain.] Dynamic Equilibrium The internal conditions of an animal’s body are never absolutely constant, but they fluctuate continuously within narrow limits. Therefore, the internal state of an animal body is best described as in dynamic equilibrium (rather than constant). However, the body compensates for these fluctuations through its control mechanisms. The net result of this activity is that physical and chemical parameters are kept within the narrow range that cells need to function. 10 Homeostasis and Hormonal control Dr M. Ellul 5.2 Hormonal control 5.2.2. Hormones Syllabus: Chemical nature of hormones and their mode of action. Peptide, protein, amine and steroid hormones (examples, but chemical formulae not required). Secondary messenger mechanism and intracellular hormone-receptor complex formation. 11 Homeostasis and Hormonal control Dr M. Ellul The Endocrine System The endocrine system consists of a number of glands that secrete hormones. It is adapted to carry information from one source to another to bring about long lasting responses. Types of glands A gland is a structure, which secretes a specific chemical substance or substances. There are two types of glands in the body: Exocrine glands Endocrine glands Exocrine glands produce secretions that are not hormones, into a duct. 12 Homeostasis and Hormonal control Dr M. Ellul Examples: Sweat gland secretes sweat into sweat ducts leading to the surface of the skin. Salivary glands release saliva into the mouth. An endocrine gland has the following characteristics: 1. Secretes chemicals called hormones. 2. Has no duct (ductless gland). Thus hormone is secreted directly into the bloodstream. 3. Has a rich blood supply. Some glands have both endocrine and exocrine functions. The pancreas functions both as an endocrine and an exocrine gland: Endocrine: Cells of the Islets of Langerhans secrete the hormones insulin and glucagon. Exocrine: Acinar cells secrete the pancreatic juice which contains the digestive enzymes into the pancreatic duct. Hormones A hormone is a regulatory chemical messenger, secreted by a gland (endocrine gland) that is released into the blood plasma, and is transported to a target organ on which it exerts its effects. 13 Homeostasis and Hormonal control Dr M. Ellul Characteristics of hormones A small organic molecule Produced in a gland, but acts at another site (target). Have no effect on the gland itself. Transported in blood. Specific to the particular target. Hormone fits to its receptors by means of a lock and key arrangement. Effective in low concentrations. Chemical nature of hormones and their mode of action Hormones are grouped into different classes based on their structure. The molecular structure must be sufficiently complex to convey regulatory information. Simple molecules are not good enough. They must also be stable enough to resist destruction prior to reaching target cells. However, they must not persist in blood for too long. Amines: These hormones are simple molecules derived from single amino acid molecule. Amines are derived from the amino acid tyrosine and are secreted from Catecholamines: the thyroid and the adrenal medulla. neurotransmitters 1. E.g. Adrenaline (epinephrine) and noradrenaline (norepinephrine) in the central and peripheral nervous are derived from tyrosine. These are both catecholamines. systems as well as 2. Thyroid hormone is also derived from tyrosine. hormones in the endocrine system Peptides: Peptides are short chains of amino acids; most hormones are peptides. They are secreted by the pituitary, parathyroid, heart, stomach, liver, and kidneys. E.g insulin, ADH, oxytocin, glucagon. 14 Homeostasis and Hormonal control Dr M. Ellul Steroids Steroids are lipids derived from cholesterol. Testosterone is the male sex hormone. Oestradiol, similar in structure to testosterone, is responsible for many female sex characteristics. Steroid hormones are secreted by the gonads, adrenal cortex, and placenta. Corticosteroids: cortisol and cortisone secreted by the adrenal cortex. 4. Fatty acids consist of 2 fatty acid carbon chains attached to a five-carbon ring. E.g. Prostaglandins (As these have a localised effect, some biologists do not consider them as hormones) 5. Glycoproteins E.g. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and Thyroid stimulating hormone. Mechanisms controlling Hormone release The mechanisms controlling the release of hormones by glands are as follows: 1. The presence of a specific metabolite in the blood e.g. excess glucose in the blood causes the release of insulin from the pancreas, which lowers the blood glucose level. 2. The presence of another hormone in the blood. For example, many of the hormones released from the anterior pituitary are ‘stimulating’ hormones. (E.g. TSH from the anterior pituitary stimulates release of T3 and T4. 3. Stimulation by neurones from the autonomic nervous system. E.g. adrenaline is released from the adrenal medulla by the arrival of nerve impulses. In the first two cases, the timing of hormone release and the amount of hormone released is regulated by feedback mechanisms. There are two types of feedback mechanisms: positive feedback and negative feedback 15 Homeostasis and Hormonal control Dr M. Ellul For example, the release of luteinising hormone under the stimulus of oestrogen is an example of positive feedback but its continued release is prevented by the later release of progesterone. Generally, the release of hormones falls under the control of the hypothalamus and pituitary gland, and the final response involves the secretion of three separate hormones. The hypothalamus controls the posterior pituitary gland which controls the endocrine glands. However, some endocrine glands are not under the control of the brain, for example, insulin secretion by the pancreas or aldosterone secretion by the adrenal glands. Hormones are carried in small concentrations. Small concentrations of hormones produce a large effect. This mechanism is called the cascade effect. Hormones do not create new biochemical processes or properties. E.g. insulin increases the permeability of the muscle cells to glucose. In the liver, glycogen is converted to glucose. Glucagon accelerates this reaction. Hormones may be categorized as Non-polar Lipophilic or lipid soluble Steroid hormones, thyroid hormones and prostaglandins Polar Hydrophilic or water soluble amino acid and peptide hormones Hormones have a high degree of target specificity. This specificity is determined by receptors on target cells. If a cell lacks a specific receptor for a hormone, the hormone will not affect the cell. 16  Homeostasis and Hormonal control Dr M. Ellul Receptors for hormones are found in two general locations on target cells: On the cell membrane hydrophilic hormones Inside the cell (usually nucleus) lipophilic hormones Hydrophilic hormones are freely soluble in blood. They however cannot pass through the membrane of target cells. They must therefore ac vate their receptors which are present on the cell membrane of the target cell from outside the cell membrane. On the other hand, lipophilic hormones travel in the blood a ached to transport proteins (to make them soluble in the blood). Their lipid solubility enables them to cross cell membranes and bind to intracellular receptors found inside the target cell. M receptor on cell memb 35B [ for hormones hydrophillic phospholipids diffuse · libid Soluble substances through the phospholipid bilayer. receptor Water · Soluble substances Do NOT either in nucleus diffuse through the phospholipid -r cytoplasm bilayer. inside the Cell 17  Homeostasis and Hormonal control Dr M. Ellul (Source: Raven et al) Lipophilic hormones Steroid hormones are lipid soluble and therefore are able to diffuse into the cell membrane and bind to receptors inside the cell. Steroid hormones alter the activity of the genes. It may take minutes to days for these hormones to exert their full effects. These hormones bind to protein receptors inside the cytoplasm/nucleus. The receptor hormone complex binds to DNA and initiates the transcription of messenger RNA from specific genes. The mRNA then moves into the cytoplasm and directs the synthesis of new proteins. I. Bind to steroid receptors in eithe cytoplasm or nucleus 18 Homeostasis and Hormonal control Dr M. Ellul In the blood, lipophilic hormones circulate bound to transport proteins. Once the hormones arrive at their target cells, they dissociate from their transport proteins Hormones diffuse through the plasma membrane. Binds to a receptor protein present only in the target cells* Hormone receptor complex enters the nucleus Binds to specific regulatory sites on the genome. These sequences are known as hormone response elements. Stimulates the transcription of specific genes to mRNA. The hormone- receptor complex may also suppress the expression of other genes. mRNA is translated to specific proteins. which do the effect. *Some steroid hormones bind to their receptors in the cytoplasm and move as a hormone- receptor complex into the nucleus. Other steroid hormones and thyroid hormones bind to the receptor in the nucleus. The proteins that result often have a regulatory function in pathway of hormone release. For example, when thyroid hormone binds to a receptor in the anterior pituitary gland, it inhibits the expression of the gene for thyrotropin. This is a negative feedback mechanism. 19 Homeostasis and Hormonal control Dr M. Ellul (Source: Raven et al) Hydrophilic hormones Peptide, protein, glycoprotein and catecholamine hormones are large and polar and therefore cannot diffuse through the plasma membrane of their target cells. These hormones react with receptors on the cell membrane. In general, hormones that bind to surface receptors trigger rapid, short-term responses. E.g. adrenaline binds to receptors on the heart muscle cells – this causes calcium channels to open and more calcium flows into the muscle cells and this increases the strength of contraction of the heart. Hydrophilic hormones bind to cell membrane receptors that are located, at least in part, on the extracellular surface of the cell membrane. Therefore, they do not directly affect the transcription of target genes, but instead initiate a signalling cascade that is carried out by a molecule called a second messenger. The hormone is the first messenger. This system is known as signal transduction. 20  Signal transduction S hormone Signalling < First messenger Cascade Another molecule · second messenger HYDROPHILLIC HORMONES ① Hormone binds to GPCR (receptor 2 G-protein activated t moves to adenylyI cyclase Second messenger Enzyme - ATP - CAMP Protein Kinase Cytoplasm Activated ATP-ADP + P Added to other # proteins * proteins got. Enzymes eg phosphorylated Homeostasis and Hormonal control Dr M. Ellul A class of hormone membrane receptors is called the G protein-coupled receptors (GPCR). The second messenger used by most hormones is cyclic adenosine monophosphate (cAMP). In the cAMP second messenger system, a water-soluble hormone binds to its receptor in the cell membrane. Step 1: This receptor is associated with an intracellular component called a G protein, and binding of the hormone activates the G-protein component. [When a hormone binds to a GPCR, the G protein is activated by Step 2: exchanging GDP (guanosine diphosphate) for GTP (guanosine triphosphate]. The activated G protein shuttles from the receptor to an enzyme called adenylyl cyclase (also known as adenylate cyclase). Step 3: adenosine triphosphate (ATP) converts to cAMP. Step 4: The cAMP which forms at the inner surface of the plasma membrane diffuses within the cytoplasm and binds to an enzyme called protein Step 5: kinase. As the second messenger, cAMP activates the protein kinase. Activated protein kinases initiate a phosphorylation cascade, in which multiple protein kinases phosphorylate (add a phosphate group to) Step 6: numerous and various cellular proteins, including other enzymes. (Source: Life: the Science of Biology) 21 Homeostasis and Hormonal control Dr M. Ellul The types of proteins phosphorylated by protein kinases vary depending on the cell type and include enzymes, membrane transport proteins, and transcription factors. This variety leads to hormones exerting unique effects in various tissues. For example, in liver cells, cAMP- dependent protein kinases trigger the activation of enzymes that facilitate the conversion of glycogen into glucose. Conversely, in cardiac muscle cells, cAMP stimulates an augmentation in both the rate and intensity of cardiac muscle contractions. E.g. Adrenaline acts via cyclic AMP to activate enzymes that break down glycogen. Summary: In the second messenger systems, when the hormone, the first messenger, binds to the receptor, the shape of the receptor is altered, triggering a series of biochemical reactions that alter the activity of the cell. In many cases, the binding of the hormone to the receptor activates an enzyme. When activated the enzyme catalyses the conversion of ATP to cyclic AMP, a nucleotide that regulates many cellular activities. Cyclic AMP is often called a second messenger, because it transfers the signal from the first messenger, the hormone, to molecules within the cell. The formation of cyclic AMP initiates a series of reactions inside the cell. Another group of hydrophilic hormone receptor is receptor tyrosine kinases (RTK). When a hormone binds to an RTK, the receptor becomes activated and phosphorylates itself. This starts off signal transduction pathways through cellular proteins that bind to phosphotyrosine. (Source: Raven et al) 22 Homeostasis and Hormonal control Dr M. Ellul Action of Hormones on Target Organs Hormones can influence: Cell membrane e.g. insulin increases the permeability of cells to glucose Enzymes of the cell When secondary messengers are used membrane e.g. Thyroxine affects the mitochondria where it influences the Organelles electron carrier system involved in the formation of ATP. e.g. steroid hormones stimulate transcription and translation Genes of particular genes. Control of Hormones The effect of hormones is controlled in two ways: 1. Negative feedback opposes their release. Example: When blood glucose level rises, the pancreas produces insulin, which causes the liver to store glucose. The stimulus for the production of insulin has thus been dampened, and insulin production stops. 2. Antagonism i.e. contrary hormones oppose each other’s actions. 23 Homeostasis and Hormonal control Dr M. Ellul E.g. Thyroid gland releases calcitonin to lower the blood calcium level, whilst the parathyroid glands release parathyroid hormone (PTH) to raise the blood calcium level. Insulin and glucagon are also antagonistic hormones. 24 Homeostasis and Hormonal control Dr M. Ellul 5.2 Hormonal control 5.2.1. The Hypothalamus Syllabus: Neurosecretory cells. Histological details not required. Release and release-inhibiting neurohormones and their action 25  Homeostasis and Hormonal control Dr M. Ellul The hypothalamus plays a dominant role in collecting information from other regions of the brain and from blood vessels passing through it. This information passes to the pituitary gland which, by its secretions directly or indirectly influences the activity of all other glands. The hypothalamus and the pituitary are responsible for the co-ordination and integration of nervous and hormonal control mechanisms. The hypothalamus is situated at the base of the forebrain below the thalamus and above the pituitary gland. It contains specialised nerve cells called neurosecretory cells. The hypothalamus receives information through nerve impulses from various brain regions. The hypothalamus also monitors levels of metabolites and hormones in the blood. Information passes to the pituitary gland either by the release of hormones or via impulses. This information passes through the neurosecretory cells. These neurosecretory cells secrete hormones that are carried by portal blood vessels directly to the pituitary gland, where they either stimulate or inhibit the secretion of hormones from the pituitary gland. Two types of hormones are released: releasing hormones and inhibiting hormones. These diffuse into blood capillaries at the base of the hypothalamus. These capillaries drain into small veins that run within the stalk of the pituitary to a second bed of capillaries in the pituitary. This system of vessels is known as the hypothalamo-hypophyseal portal system. Many hormones released from the hypothalamus stimulate the pituitary gland to produce a second set of hormones: e.g. Thyrotrophin releasing hormone stimulates release of thyroid stimulating hormone. info o hypothalamus metabolites T info from other Dituitary gland - parts of the brain ~ D integration = and coordination of nervous and T ⑪Tle& hormonal conheal info on & / / I hormones - mechanisms START3 ~ 26 Homeostasis and Hormonal control Dr M. Ellul 5.2 Hormonal control 5.2.3. The pituitary gland Syllabus: Anterior hormone-producing lobe; prolactin and tropic hormones. Posterior non-producing lobe; ADH and oxytocin. Effects of these hormones only are required; detail of structure is not required. 27 Homeostasis and Hormonal control Dr M. Ellul The pituitary gland (hypophysis) is divided into two lobes: anterior pituitary posterior pituitary The Anterior Lobe - Adenohypophysis The anterior lobe has a glandular origin and is functionally connected to the brain by the hypothalamo-hypophyseal portal system. It consists of endocrine cells that synthesize and secrete several hormones directly into blood. Neurosecretory cells in the hypothalamus control the anterior pituitary by secreting 2 kinds of hormones into the blood: Releasing induce the anterior pituitary to secrete its hormones: hormones. Inhibiting prevent the anterior pituitary from secreting its hormones: hormones. hypothalamus neurosecretory cells - produce releasing hormones or inhibiting hormone + release them into the hypothalamo- The anterior pituitary produces hydrophysi and stores 6 hormones: FSH, Part al System LH, prolactin, thyroid + reach stimulating hormone, the antier adrenocorticotrophic hormone i or and growth hormone. pituitary lobe. + stimulates it to produce its own hormones. 28 Homeostasis and Hormonal control Dr M. Ellul Hypothalamic hormone Anterior pituitary hormone and Site of action response Growth hormone releasing factor (GHRF) Growth hormone release- Growth hormone Most tissues inhibiting hormone (GHRIH) (somatostatin) Prolactin releasing factor Prolactin (luteotrophin)(LTH) (PRF) Ovary and Prolactin inhibiting factor Inhibition of prolactin secretion mammary gland (PIF) Luteinising hormone Follicle stimulating hormone Ovary and testis releasing hormone (LHRH) Luteinising hormone (LH) Thyrotrophin releasing Thyroid stimulating hormone Thyroid gland hormone (TRH) (TSH) Adrenocorticotrophin Adrenocorticotrophin hormone Adrenal cortex releasing factor (CRF) (ACTH) Many anterior pituitary hormones are termed tropic hormones because they stimulate the secretion of hormones by other endocrine glands elsewhere in the body, thus exerting a regulatory effect on those glands. [Tropic hormones are released by an endocrine gland and act upon another endocrine gland. Trophic hormones stimulate growth in target tissues.] 29  Homeostasis and Hormonal control Dr M. Ellul The posterior lobe - Neurohypophysis As the posterior lobe receives ends of neurosecretory cells from the hypothalamus, it is considered as an extension of the hypothalamus itself. The posterior pituitary (neurohypophysis) does not synthesise any hormones but stores and releases 2 hormones: I released in response to a fall in the water Antidiuretic content of plasma and leads to an increase in the permeability to water of hormone - the distal and collecting tubules of the nephron causes contraction of the uterus during birth and facilitates the release of milk - Oxytocin from the mammary glands during breastfeeding produced by but · hypothalamus Stored + released by the posterior pituitary. 30 Homeostasis and Hormonal control Dr M. Ellul 31 Homeostasis and Hormonal control Dr M. Ellul 5.2 Hormonal control 5.2.4. Pancreas and adrenals - Fif Syllabus: Regulation of blood glucose levels. Insulin and glucagon; site of secretion (beta and alpha cells). Regulatory processes in lowering or raising blood glucose. Diabetes – Type II (insulin-independent or maturity onset diabetes) and its control. Role of adrenalin in blood glucose regulation. (Recall Type I [Juvenile or insulin-dependent] diabetes in Section 5.6.3] Role of Adrenalin and Cortisol in blood glucose regulation. 32 Homeostasis and Hormonal control Dr M. Ellul Control of blood glucose levels What hormones are involved in the homeostasis of blood sugar? Why? All living things use glucose as a source of energy. In vertebrates it is cri cal that the levels of glucose in the blood are consistent. Small fluctua ons are fine, but if the glucose concentra on in the blood gets too high, a coma could result. If the glucose concentra on in the blood gets too low, the person could experience seizures, go into a coma or die. In humans, hormone levels help regulate the glucose concentra on in the blood and keep us in homeostasis. 1. The rela ve blood concentra ons of which three molecules are recorded in the graph? Glucose insulin and - glucagon 2. Which molecule is found in the blood at the highest concentra ons? Glucose 3. Why do cells need glucose? To respire. (production of ATP( 4. According to the graph, what happens to blood glucose levels a er a meal has been eaten? Increase 5. a. As blood glucose levels increase above baseline, the level of which hormone also increases? Insulin b. As blood glucose levels begin to drop below baseline, the concentra on of which hormone increases? Glucagon c. As blood glucose returns to its baseline level, what happens to the levels of insulin and glucagon in the blood? They stabilise (Adapted from: POGIL™ Activities for AP* Biology 33  Homeostasis and Hormonal control Dr M. Ellul The normal human blood glucose concentration is about 90 mg per 100 cm3 of blood. This set point is genetically determined. The pancreas The pancreas is the organ, which mostly regulates the blood glucose level. The pancreas has both exocrine and endocrine functions and is associated with the alimentary canal. The bulk of the gland is composed of acinar cells (exocrine). Interspersed amongst groups of acinar cells are the islets of Langerhans containing a small number of α cells and numerous β cells and blood capillaries. α cells secrete glucagon while β cells secrete insulin. These 2 have antagonistic effects on the blood glucose level. ISLETS OF Endocrine LUNGER- = · B cellS HANS > insulin B - -- Po < ↳ cells · > O glucagon - D & I a cinar cells exocrine have a pancreatic duct Digestion Insulin: compensates for high levels of glucose. Glucagon: compensates for low levels of glucose. Insulin Insulin is a small protein composed of 51 amino acids. Insulin consists of two chains: the 21- residue A chain and the 30-residue B chain. It is released when there is a rise in blood glucose level to above 100 mg/ 100 cm3 blood and a rise in glucagon level. It is carried in the plasma bound to β -globulin. Secreted by Beta cells in the Islets of Langerhans in the pancreas. Mode of action Insulin binds to a glycoprotein receptor (Receptor Tyrosine Kinase (RTK)) on the cell surface. It exposes a cytoplasmic protein kinase active site and the insulin receptor self- phosphorylates. This is a protein kinase signal which targets insulin response substrates and many cellular responses are initiated. Beneath the plasma membrane there are intracellular vesicles containing the Glucose Transporter Proteins (GLUT proteins). On attachment of insulin to the receptor, there is exocytosis of the vesicles, and the GLUT proteins are released and attach to the plasma membrane. This leads to changes in the cell membrane permeability. The rate of facilitated diffusion of glucose into the target cells increases as a result of the increase in GLUT proteins. When insulin is removed, there is endocytosis of the GLUT proteins. 34 Homeostasis and Hormonal control Dr M. Ellul Insulin causes activation of an enzyme known as glucokinase which phosphorylates glucose, trapping it inside cells. Insulin also causes the activation of another enzyme, glycogen synthase which converts glucose into glycogen in a process known as glycogenesis. It reduces in the amount of glucose in blood due to: 1. An increase in the uptake of glucose into cells especially skeletal muscles. 2. An increase in the rate of cellular respiration and the use of glucose as a respiratory substrate. 3. An increase in the conversion of glucose to fat in adipose cells. 4. An increase in the rate of uptake of amino acids into cells and the rate of protein synthesis. 5. An increase in the rate of conversion of glucose to glycogen in liver and muscle cells (glycogenesis). Glucose to glycogen 6. Decrease in the formation of glucose (gluconeogenesis). Insulin appears to affect all cells, but muscle, fat and liver cells are its main targets. Regulation of Insulin production Insulin production is regulated by a negative feedback mechanism. When the blood glucose concentration increases to above the normal range it is detected by the β cells in the pancreas. When the concentration of glucose is high glucose molecules enter the β cells by facilitated diffusion. The cells respire this glucose and produce ATP. High concentrations of ATP cause the potassium channels in the β cells to close, producing a change in the membrane potential. This change in the membrane potential causes the voltage-gated calcium channels to open. In response to the influx of calcium ions, the β cells secrete the hormone insulin. Insulin-containing vesicles move towards the cell-surface 35 Homeostasis and Hormonal control Dr M. Ellul membrane where they release insulin into the capillaries. Once in the bloodstream, insulin circulates around the body. As insulin levels rise, glucose is removed from the blood. As blood glucose level decreases, the β cells reduce output of insulin. 3 negativeven Effects of insulin deficiency and excess Deficiency Excess Blood glucose level above set point. Blood glucose level below set (Hyperglycaemia) point. (Hypoglycaemia) Breakdown of muscle tissue. Hunger. Loss of weight. Sweating. Tiredness. Irritability. Damage to blood vessels, kidney and nerve Palpitations. supply to lower limbs. Glucagon Glucagon is a peptide composed of 29 amino acids and is released in response to a fall in blood glucose level. It is released by the Alpha cells in the Islets of Langerhans. Mode of action When glucagon binds to receptors in liver cells:  It activates adenyl cyclase to form cyclic AMP. This activates phosphorylase enzymes that catalyse the breakdown of glycogen to glucose (glycogenolysis).  It increases the conversion of amino acids and glycerol into glucose - 6 - phosphate.  It increases gluconeogenesis i.e. the synthesis of glucose from non-carbohydrate sources. (Note: Glucagon has no effect on muscle glycogen.) 36 Homeostasis and Hormonal control Dr M. Ellul primary - messenger. transduction Signal (2 messenger ( cyclicamp sis Glycogedly - Negative feedback control 37 Homeostasis and Hormonal control Dr M. Ellul What are three of the organs/ ssues of the body that interact to regulate blood glucose levels? liver - pancreas : other cells According to the model shown, where in the body do the insulin and glucagon originate? Pancreas Refer to diagram: a. What shape represents glucose? nexagon b. Describe how glycogen is related to glucose. glycogen is a polymer of glucose. c. Which form of sugar, glucose or glycogen is stored in the liver for future use? Glycogen. Read This! Most cells in the body have insulin receptors. When insulin is present, the transfer of glucose into cells increases. This takes the glucose out of the bloodstream and puts it where it can be used, or in some cases stores it as glycogen. The glycogen can be converted back into glucose when it is needed. But glycogen cannot be used by cells directly as an energy source. Excess glucose that remains in the blood gets excreted out in urine. Refer to the diagram above: a. In which cycle is glucose removed from the blood by storing it or moving it into cells to use for fuel? Cycle A b. Which hormone, insulin or glucagon, helps glucose move into cells of the body? Insulin c. In which cycle is glucose added to the blood from storage areas? cycle B d. Which hormone, insulin or glucagon, helps turn glycogen into glucose? Glucagon e. Explain the role of insulin in maintaining glucose levels after a large meal. After a large meal glucose in blood increases : insulin is released Glucose- (liver) be used up for respiration > Glycogen f. Explain the role of glucagon in maintaining glucose levels when the organism is hungry. Hunger : blood glucose glucagon released + changes glycogen > - glucose : Blood glucose g. For each of the cycles in the diagram identify the stimulus and response for the feedback loops and indicate whether the feedback loop is positive or negative feedback. Stimulus Response Positive or Negative? Cycle Ahigh blood glucose feedback level insulin released negative Cycle B low blood glucose level glucagon released negative feedback Predict the levels of glucose, glucagon, and insulin in a person who has: a. Skipped a meal. low glucose-high glucagon-low insulin low b. Just run 5 miles. glucose-high glucagon-low insulin insulin c. Just ate a large dinner. high glucose-lowglucagon-high (Adapted from: POGIL™ Ac vi es for AP* Biology) 38 Homeostasis and Hormonal control Dr M. Ellul Other glucose control mechanisms Besides glucagon, other hormones increase blood glucose concentrations: Adrenaline is secreted from the adrenal gland in response & to low blood glucose concentration, exercise and stress. Adrenaline binds to receptors on the liver cell membrane. Adrenaline induces two reactions in the liver cells:  Activation of glycogenolysis (glycogen → glucose).  Inhibition of glycogenesis (glucose → glycogen). Adrenaline also promotes secretion of glucagon from the pancreas and inhibits secretion of insulin. Cortisol secreted by adrenal glands, promotes liver cells to convert amino acids and glycerol to glucose when glycogen stores in the liver are exhausted. Diabetes mellitus Diabetes mellitus is a metabolic disorder caused by a lack of insulin or a loss of responsiveness to insulin. May result from incomplete development of, damage to, or disease of the Islets of Langerhans. Diagnosis Excretion of large amounts of sugary urine as blood glucose concentration becomes too high. This occurs since the kidney is unable to reabsorb all the glucose filtered into its tubules back into the blood. Other symptoms include intense thirst, hunger and extreme tiredness. 39 Homeostasis and Hormonal control Dr M. Ellul Types of Diabetes mellitus Type I (insulin dependent) The pancreas does not produce insulin. This is possibly due to an autoimmune disorder that destroys the Islets of Langerhans. Generally, appears before the age of 40, often diagnosed in childhood (juvenile diabetes). If condition is untreated it may result in a lethal diabetic coma. Generally type I diabetes is treated through a combination of planned diet, exercise, glucose monitoring and a daily insulin injection. Type II (non-insulin dependent) This condition arises when the:  Pancreas produces a low amount of insulin.  Body cells do not respond to insulin. The symptoms often show above the age of 40 (adult onset diabetes). It is best controlled through a low fat diet and regular exercise. If this fails, oral drugs may be used to make cells more sensitive to the effects of insulin or stimulate pancreas to secrete more insulin. 40 Homeostasis and Hormonal control Dr M. Ellul In the past, diabetes mellitus was diagnosed by tasting the urine of the patient. What evidence for diabetes were the doctors looking for? In Type I diabetes, the Beta cells of the pancreas produce little to no insulin. What effect does this have on an organism’s ability to regulate blood glucose levels? Type I diabetics must eat frequent small meals. Explain why this is necessary using what you have learned about blood glucose regulation. Other symptoms of Type I diabetes are increased thirst and frequent urination. Explain these symptoms using what your knowledge on diabetes mellitus together with knowledge of osmosis and diffusion. Source: POGIL™ Ac vi es for AP* Biology 41 Homeostasis and Hormonal control Dr M. Ellul Principal Hormones of Humans Hormone Stimulus for Secretion Location of endocrine Target organ/cells Effect/s gland Gastrin Presence of protein in G cells in the mucosa of Parietal cells in the Secretion of gastric acid HCl; increases gastric the stomach the stomach and first stomach; stomach motility part of duodenum muscle CCK Contact with content of The duodenum Gall bladder; Gall bladder contract and eject bile; pancreas (cholecystokinin) stomach pancreas secretes digestive enzymes Secretin Presence of HCl from The duodenum and Liver and pancreas Pancreas secrete alkaline pancreatic juice and the stomach in jejenum stimulates bile production in the liver. duodenum and Jejenum Adrenaline Stressful situation Medulla of the adrenal Heart, skeletal Increase heart activity; improves power and (epinephrine) requiring flight or fight gland muscle, respiratory prolongs the action of muscle; increase rate system and depth of breathing; reduce blood supply to Gastro Intestinal tract Noradrenaline Stressful situation Medulla of the adrenal Heart; liver; Increase heart rate; stimulate release of (norepinephrine) requiring flight or fight gland glucose from energy reserves ADH/vasopressin Reduction in blood Posterior pituitary Collecting ducts of Reabsorption of water by the kidneys; plasma volume; kidney nephron; constriction of blood vessels increased plasma blood vessels osmolarity Oxytocin Pressure in cervix of Posterior pituitary Smooth muscle of Contraction of smooth muscle of uterus during uterus; suckling uterus; mammary birth; expulsion of milk during suckling glands Insulin High blood glucose Beta cells of the islets Muscle fibres Uptake of glucose by muscle, fat and liver cells concentration of Langerhans in the Adipose cells and pancreas liver cells 42 Homeostasis and Hormonal control Dr M. Ellul Glucagon Low blood glucose alpha cells of the islets Liver Hydrolysis to glycogen to glucose in the liver - concentration of Langerhans in the glycogenolysis pancreas Cortisol Fasting state; ACTH Adrenal cortex Liver; immune Synthesis and storage of glucose; prevents system inflammation; regulates deposition of fat in body. Thyroid stimulating Thyrotrophin-releasing Anterior pituitary Thyroid gland Controls synthesis and secretion of thyroxine hormone hormone from and triiodothyronine hypothalamus Adrenocorticotropic Increase corticotrophin Anterior pituitary Cortex of Adrenal Controls secretion of corticosteroids hormone ACTH –releasing hormone glands Growth hormone Growth hormone Anterior pituitary Long bones, fat cells Growth in length of long bones; stimulate releasing hormone protein synthesis and metabolism of fat; from hypothalamus; falling blood glucose concentration FSH Gonadotropin-releasing Anterior pituitary Graafian follicle; Ripening of Graafian follicle and release of ova; hormone (GnRH) from Testis Formation of sperm; hypothalamus Development in puberty; LH (also known as Gonadotropin-releasing Anterior pituitary Testes; ovaries Production of sex hormones in males; ICSH) hormone (GnRH) from ovulation, progesterone synthesis and corpus hypothalamus luteum formation in females; prolactin Suckling Anterior pituitary Mammary glands; Secretion of milk by mammary glands; corpus corpus luteum; luteum secrete progesterone; MSH Dark environment Anterior pituitary Skin; immune Skin colour; anti-inflammatory; appetite system; suppression; stimulate sexual activity; heart rate and blood pressure testosterone LH Testes (ovaries; Testes Development of testes; secondary sexual adrenals) characteristics in males 43 Homeostasis and Hormonal control Dr M. Ellul Oestrogen FSH Ovaries; placenta Mammary glands; Female secondary sexual characteristics; (adrenals and testes) uterus thickening on endometrium; oestrous/menstrual cycle; Progesterone LH and prolactin Corpus luteum; Uterus Prepares uterus for implantation; prevents placenta ovulation in pregnancy; Human chorionic Pregnancy Placenta Corpus luteum Maintains it gonadotrophin Prostaglandins Cell membranes Smooth muscle Contraction including uterine muscle to induce labour Aldosterone ACTH /reduced blood Adrenal cortex Distal tubule and Controls excretion of sodium in the kidney to pressure collecting ducts of maintain balance of salt and water in the body kidney fluids Thyroxine/thyroid TSH from anterior Thyroid gland Every cell of body Regulates metabolism, increase protein hormone pituitary synthesis, regulates protein, fat and carbohydrate metabolism 44 Homeostasis and Hormonal control Dr M. Ellul Self-assessment 1. How are the endocrine and nervous systems similar? How are they different? 2. What are hormones? 3. How does a lipophilic hormone stimulate action in a cell? 4. How does a hydrophilic hormone stimulate action in a cell? 5. What is the role of the hypothalamus in regulating hormone secretion? 6. Why are most of the hormones secreted by the pituitary gland tropic hormones? 7. Explain the role of the pancreatic hormones in controlling blood glucose levels. 45