Introduction to Endocrinology (PHYS) PDF

PHR1001M Introduction to Endocrinology (PHYS) Professor Terence P. Herbert email: [email protected] Intended Learning Outcomes  Define what endocrinology is and what a hormone is.  Describe the properties of hormones  State the similarities and differ...

PHR1001M Introduction to Endocrinology (PHYS) Professor Terence P. Herbert email: [email protected] Intended Learning Outcomes  Define what endocrinology is and what a hormone is.  Describe the properties of hormones  State the similarities and differences between the endocrine and nervous systems  Name the major endocrine organs/tissues, name the hormones they release and the function of these hormones.  Name examples of diseases caused by hypo- and hyper- function of an endocrine organ or gland  Give examples of water and lipid soluble hormones, describe how they are synthesised and what receptor types they activate.  Understand the concept of negative feedback and its role in homeostasis Reference materials Human Physiology Silverthorn Human Physiology Sherwood Principles of Physiology Berne and Levy Biological communication  In multicellular organisms, like ourselves, it is essential that cells are able communicate with each other to mount co-ordinated responses (e.g. growth, development, metabolism, movement etc) and to maintain homeostasis (e.g. glucose, calcium, pH)  Homeostasis - keeping the internal environment of the body in balance (homeo = 'body' and stasis = ' the same‘) Comparison between the nervous and endocrine systems There are two major communication systems in the body: The endocrine system The nervous system Nervous system Endocrine system Communicates over short and long Communicates over short and long distances distances ‘Wired’ (network of neurones) ‘wireless’ (network of blood vessels) Chemical signal at target cell Chemical signal in blood Rapid Slow Brief duration of signal Long duration of signal Signal are Neurotransmitters Signal are Hormones Endocrinology  Endocrinology is the study of hormones  The endocrine system communicates between cells and organs using hormones (hormones are the messengers!)  Classically hormones are secreted from endocrine organs into the blood and exert their effect on a distal target.  Hormones regulate many diverse functions and often are essential in maintaining homeostasis  Function in controlling growth, development, metabolism, temperature, H2O balance, reproduction……  Hormones exert their effects at low concentrations i.e. in the nanomolar (10-9M) to picomolar (10-12M) range Endocrine signalling 1. Hormone secreted from an endocrine cell/organ into the extracellular fluid; 2. Hormone diffuses into the vasculature where it can circulate throughout the body; 3. The hormone diffuses out of the vascular compartment into the extracellular space 4. The hormone binds to its specific receptor within/on cells of a target organ. 5. Binding of hormone to receptor triggers a response 2. 3. 4. 1. 5. Mechanisms for cell-to cell signalling via hormones Chemical messenger Chemical messenger Chemical messenger released from cell and released from cell and released from cell and travels via the blood to acts acts on the same cell acts on target cell a on a distant target cell short distance away Classification of hormones Hormones can be:  Proteins/peptides  Steroids  Amines See additional slides at the end of this lecture Hormones  Hormones exert their effect by binding to receptors and regulating…. 1. The rate of enzymatic reactions 2. The transport of ions and molecules across cell membranes 3. Gene expression and the synthesis of proteins 4. Electrical signalling pathways Homeostatic systems- Production and release of hormones are regulated by feedback mechanisms  Negative feedback mechanisms are essential to maintain homeostasis.  There are two basic configurations of negative-feedback loops within the endocrine system:  Physiological response-driven feedback loop (referred to simply as "response-driven feedback")  Endocrine axis-driven feedback loop –this is where the hormone is regulated by the concentration of the hormone in the blood not the response to the hormone Production and release is regulated by a negative feedback mechanisms The response-driven feedback loop -regulating for example blood glucose levels (pancreatic islets), blood Ca++ and Pi levels (parathyroid glands, kidney), blood osmolarity and volume (hypothalamus/posterior pituitary), and blood Na+, K+, and H+ (zona glomerulosa of the adrenal cortex and atrial cells) High glucose Release of insulin and uptake of glucose Lower glucose Endocrine axis-driven feedback loop  This is where the hormone is regulated by the concentration of the hormone in the blood and not the response to the hormone The hypothalamus plays an important role in the synthesis and secretion of pituitary hormones.  Some hormones released from the hypothalamus act on the pituitary gland to stimulate the release of pituitary hormones  These pituitary hormones act on endocrine glands to stimulate hormone release  Concentration of hormone in blood regulated by feedback mechanism controlled by the level of hormone in the blood (i.e. the endocrine axis feedback loop) Hormones Hormones are secreted from…..  Endocrine glands/tissues…..Specialised structures or groups of cells which secrete hormones  Endocrine cells - specialised cells which secrete hormones  Neuroendocrine cells - (neurohormones - released from neurones into the blood) The Major Endocrine Glands/tissues Hypothalamus The hypothalamus synthesises 9 hormones  7 are secreted and control the release of hormones from the anterior pituitary.  Examples include:  Thyrotropin-releasing hormone (TRH)- act on anterior pituitary and stimulates the release of thyroid stimulating hormone  Growth hormone-releasing hormone (GHRH) acts on anterior pituitary and stimulates the release of thyroid stimulating hormone  2 hormones are made in the hypothalamus but secreted from the posterior pituitary  Vasopressin (o.n.a. antidiuretic hormone (ADH))  Oxytocin Pineal Gland  Pea-sized conical mass of tissue behind the third ventricle of the brain.  Its shape resembles a small pine cone (hence its name)  Releases the hormone melatonin an amine released during ‘dark cycles’.  Melatonin helps maintain sleep patterns (the biological clock/circadian rhythms/day-night cycles)  The pineal gland is not isolated from the body by the blood–brain barrier system Pineal Gland Pituitary Gland  A pea-sized body attached to the base of the brain  Major endocrine gland often referred to as the "master gland.“  Pituitary is divided into two distinct tissues the ANTERIOR and POSTERIOR pituitary gland  The ANTERIOR pituitary gland produces several hormones important in controlling metabolism, reproduction, growth, and development e.g. DROWTH HORMONE.  The POSTERIOR pituitary secretes hormones made by the hypothalamus e.g. vasopressin The thyroid gland  It is located at the front of the neck.  The thyroid secretes the thyroid hormones thyroxine (T4) and tri-iodothyronine (T3)  Thyroid hormones control metabolism, blood pressure, heart rate, digestion, and reproduction. The thyroid gland also releases the hormone calcitonin –this inhibits release of calcium from the bones. The importance of this hormone in humans is unclear The Parathyroid Gland  The parathyroid gland is a group of four small glands located behind the thyroid gland.  Releases the hormone parathyroid hormone.  Parathyroid hormone is vital for calcium homeostasis through its effects on bone, kidney, and intestine. The Thymus Gland  The thymus gland is located behind the sternum and between the lungs.  It is only active until puberty.  This gland secretes the hormone Thymosin  Thymosin is important in the development of T-cells. Adrenal Glands  This gland are found on the top of the kidneys.  Organ consist of a two different tissues: ADRENAL CORTEX and ADRENAL MEDULLA Hormones made by the adrenal cortex.  Glucocorticoids (e.g. CORTISOL)- Part of stress response, increase blood glucose levels and decrease immune response.  Aldosterone - Regulates sodium content in the blood. Hormones made by the adrenal medulla  Adrenaline - Stimulates “fight or flight” response. Pancreas  The pancreas is a large gland located behind the stomach.  Hormones are produced by the endocrine pancreas.  Beta cells within the endocrine pancreas synthesises the hormone INSULIN  Alpha cells within the endocrine pancreas synthesises the hormone GLUCAGON  Insulin and glucagon are important in controlling blood glucose ( i.e. glucose homeostasis  Insulin deficiency results in diabetes mellitus Ovaries and testes Ovaries  Produce two hormones: oestrogen and progesterone  These hormones promote the development of sexual characteristics and are essential for the menstrual cycle and reproduction. Testes  Produces the hormone testosterone  Testosterone promotes male sexual characteristics and is essential for reproductive function Summary of hormones and their functions Gland Hormones Functions Thyroid Thyroxine Regulates metabolism Calcitonin Inhibits release of calcium from the bones Parathyroids Parathyroid hormone Stimulates the release of calcium from the bones. Islet cells (in Insulin Decreases blood sugar by promoting uptake of glucose by cells. the pancreas) Glucagon Increases blood sugar by stimulating breakdown of glycogen in the liver. Testes Testosterone Regulates sperm cell production and secondary sex characteristics. Ovaries Estrogen Stimulates egg maturation, controls secondary sex characteristics. Progesterone Prepares the uterus to receive a fertilized egg. Adrenal Adrenaline Stimulates “fight or flight” response. Medulla Adrenal Glucocorticoids Part of stress response, increase blood glucose levels and decrease Cortex (CORTISOL) immune response. Aldosterone Regulates sodium content in the blood. Testosterone (in both Adult body form (greater muscle mass), libido. sexes) Pineal gland Melatonin Sleep cycles, reproductive cycles in many mammals. Hormones Hormones are secreted from…..  Endocrine glands/tissues…..Specialised structures or groups of cells which secrete hormones  Endocrine cells - specialised cells which secrete hormones  Neuroendocrine cells - (neurohormones - released from neurones into the blood) Endocrine disorders  Types of Endocrine Disorders: Endocrine disease results from an elevation or a drop in an endocrine hormone (hormone imbalance). Endocrine diseases are often caused by: Autoimmune attack Lesion or tumour Genetic mutation Classification of endocrine disorders  Endocrine disorders can be classified according to the intensity of hormonal activity:  Hyperfunction: characterised by an increase in the concentration of a hormone (or hormones) in the blood.  Hypofunction: characterized by decreased concentration of a hormone in the circulating blood. Hyperfunction….too much  Acromegaly or Gigantism  High amounts of growth hormone leads to fast and abnormal bone growth.  Hyperthyroidism.  Excessive production of thyroid hormone  Symptoms include irritability, muscle, weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhoea, enlargement of the thyroid (goitre) and weight loss, bulging eyeballs. Hypofunction.....too little Addison's Disease lack of the steroid hormones, cortisol and aldosterone. Symptoms: Extreme fatigue, Weight loss and decreased appetite, Darkening of your skin (hyperpigmentation), Low blood pressure, Low blood sugar (hypoglycaemia), Nausea, diarrhoea or vomiting, abdominal pain, Muscle or joint pains Diabetes Mellitus lack of insulin Symptoms: Weight loss, fatigue, thirst, hunger For reference only: http://www2.highlands.edu/academics/divisions/scipe/biology/faculty/harnden/2122/notes/endo.htm The next few slides contains information that you need to learn. Supplement this with notes through summarising the appropriate text on this subject that can be found any of the following text books: Human Physiology (Silverthorn) Human Physiology (Sherwood) Principles of Physiology (Berne and Levy) Classification of hormones Hormones can be:  Proteins or peptides  Steroids  Amines Protein/Peptide hormones  Peptides – These are small proteins ranging from 3 to approximately 50 amino acid. Thyrotropin Releasing Hormone 3AA and insulin are examples of peptide hormones  Proteins – Examples include growth hormone and prolactin each have nearly 200 amino acid residues  Glycoproteins - These are protein hormoes which are glycosylated. This a post-translational medication where sugar moieties attached in the ER. Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) are examples. Protein/peptide hormones Facts about protein/peptide hormones:  Processing of a prohormone into  They are water soluble an active hormone through the action of proteases  Bind extracellular receptors  Made at Endoplasmic Reticulum (ER) as an inactive hormone (prohormone)  Processed to active hormone by enzymes (proteases)  Active hormone is stored in secretory vesicles  The hormone is released from cell in response to an appropriate stimuli. This process of regulated secretion is called exocytosis  The Half life is short – often minutes Packaged into vesicles Steroid hormones Facts about steroid hormones:  They are Lipid soluble (examples include testosterone and cortisol)  Synthesised from cholesterol  These are made in the smooth endoplasmic reticulum (ER) Steroids are lipophilic and can pass through membranes. Therefore, they cannot be stored and must be synthesised when needed They are in insoluble, so are carried through the blood bound to proteins (carrier molecules) They often bind to intracellular or nuclear receptors They often regulate gene expression Amine hormones Derived from the amino acid Tyrosine  Catecholamines- Adrenaline (epinephrine) – one tyrosine Made in the adrenal gland (medulla) Water Soluble and binds to cell surface receptors (GPCR).  Thyroid hormones - two tyrosine molecules and iodine. Water insoluble - bind to intracellular nuclear receptors. T3 and T4 bind to the thyroid hormone receptor Derived from the amino acid tryptophan  Melatonin binds a cell surface receptor (GPCR) Amine hormones Noradrenaline Adrenaline Adrenal Medulla/neurones Thyroid Gland Task 1 : Fill in the blanks… (5 min) Gland Hormones Functions Thyroxine Regulates metabolism Calcitonin Parathyroids Parathyroid hormone Islet cells (in Decreases blood sugar by promoting uptake of glucose by cells. the pancreas) Glucagon Testes Regulates sperm cell production and secondary sex characteristics. Estrogen Progesterone Prepares the uterus to receive a fertilized egg. Adrenal cortex Stimulates “fight or flight” response. Adrenal Part of stress response, increase blood glucose levels and decrease medulla immune response. Aldosterone Testosterone (in both Adult body form (greater muscle mass), libido. sexes) Pineal gland Sleep cycles, reproductive cycles in many mammals.