Introduction to Endocrinology - Student Copy(2).pptx

Introduction to Endocrinology BSMS203: Theme 1, Lecture 1 Oliver Steele [email protected] Join at slido.com #5314177 Lecture in Context Introductio n to Endocrinolo gy You are here! • Understand the normal physiology of the endocrine system Series of Endocrine Physiology Lectures • Physiology...

Introduction to Endocrinology BSMS203: Theme 1, Lecture 1 Oliver Steele [email protected] Join at slido.com #5314177 Lecture in Context Introductio n to Endocrinolo gy You are here! • Understand the normal physiology of the endocrine system Series of Endocrine Physiology Lectures • Physiology integral to understanding disease progression and treatment • Complimented by both anatomical and clinical teaching given by others 2 Intended Learning Outcomes To gain a basic understanding of the endocrine system, including an introduction to the terminology and the physiology of normal endocrine function 3 Outline 1. Gross anatomy • Overview of endocrine glands and their hormones 2. • • 3. • • 4. • Hormone characteristics Comparison of peptide and steroid hormones Hormone transport Mechanisms of action Hormone receptors and second messengers Mechanisms of hormone action Endocrine self-regulation Regulation of hormone secretion (feedback control, neuroendocrine interactions, primary vs secondary endocrine dysfunction) 4 Gross Anatomy of the Endocrine System Section 1 of 4 ‘Top-down’ Gross Anatomy Pituitar y Gland Thyroi d Gland Adren al Gland Pancreas Reproduct ive Organs 6 Anterior and Posterior Pituitary Gland Pituitary Gland = Hypophysis Functionally and anatomically distinct lobes Nervous Innervatio n Hypothala mus Pituitary (Hypophy sis) Anterior Lobe Hypophyse al Veinous Blood Drainage Hypophys eal Arterial Blood Supply Posterior Lobe 7 Hypophyseal portal system connects the hypothalamus to the pituitary gland The pituitary gland sits at the ventral surface of the brain, encased in an enclosure of sphenoid bone Sometimes referred to simply as the ‘master gland’ Pituitary pathophysiology • Sultan Kösen, age 39 • Aged 27, Sultan was 8ft 3” • Roughly 250cm • Benign tumour on their pituitary gland causing the gland to release excessive levels of growth hormone • Acromegaly & Gigantism Sultan Kösen • Gamma knife surgery in 2010, preventing further growth 8 Thyroid Gland Anterior Production of the main thyroid hormones T3 and T4, as well as Calcitonin Posterior Larynx Thyroid Thyroid Hormones are important for; • Trachea • Parathyr oid Cellular Metabolic Rate Regulation Calcium Homeostasis Iodine metabolism • • • 9 150 μg for adults 200 μg during pregnancy 90 μg for children Thyroid pathophysiology Hyperthyroidism (too much) • Weight loss • Difficulty sleeping • Protruding eyes (exophthalmos) • Driven by too much thyroid hormone, leading to a hyper-active metabolism Hyperthyroid ism Hypothyroidism (too little) • Weight gain • Tiredness • ‘Puffy’ swollen face • Driven by too little thyroid hormone, leading to a hypo-active metabolism T3 T3T3 T3T3 Hyperthyroi dism Hypothyroi 10 dism Hypothyroid ism Adrenal Gland Located just above the kidneys • In US English adrenal = suprarenal Divided into two clear regions, the cortex and the medulla Medulla • Medul la Corte • x Inner most region of the adrenal gland Production of adrenaline and other hormones involved in the fight-orflight response Cortex • • 11 Outer layer of the adrenal gland Stress hormone (cortisol) and sex hormones (estrogen and androgens) Adrenal pathophysiology Context & Interest • Jordy Cernik, age 47 • Cushing Syndrome • Excessive production of cortisol from the adrenal gland • High blood pressure • Excessive weight gain • Bone density loss Peter (Jordy) Cernik, Youtube 12 Pancreas Exocrine Role • Secretion of digestive enzymes into the gastrointestinal tract Islets of Langerhans Stoma ch Endocrine Role • Secretion of hormones into the blood Hormones are produced by specialised cells, clustered in Islets of Langerhans • • • • • Pancreas Duodenu m Pancreatic Duct α cell – glucagon β cell – Insulin δ cell – Somatostatin ε cell – grehlin PP cell – Pancreatic polypeptide Function of these hormones are largely around the processing of ingested food • Cellular nutrition • Nutrient metabolism, storage and uptake 13 Pancreatic pathophysiology • Patient JL, age ~3-4 • Type 1 Diabetes Mellitus (T1DM) • Insufficient insulin production • Diabetes mellitus – latin for ‘honeyed siphon’ (or ‘to pass through’), or honeyed urine • Cells assume starvation state due to low glucose uptake and seek alternate sources of energy 14 Reproductive Organs Gonads are the site of gametogenesis • Source of biological replication material (ie, eggs and sperm) Hormones produced by the gonads • Progesterone • Estrogen • Testosterone Ovaries Androgens & Estrogens Roles include Testes • • • • • 15 Menstrual cycle Fertility Puberty Aggression Body composition Manipulated androgenic physiology Anabolic androgenic steroids (AAS) • Relating to the synthesis of protein that aids muscle growth, metabolic enhancement and performance • Designed to mimic the action of testosterone • Misused in competitive sports performance • Enhanced performance • Risks of steroid misuse relate to disrupted sex-specific hormonal signalling In • • • men … Reduced sperm count Infertility Erectile dysfunction In • • • women … Facial hair growth Hair loss Deepened voice 16 Lance Armstrong Which endocrine gland is responsible for the secretion of growth hormone? 1. 2. 3. 4. Pancreas Pituitary Thyroid Ovaries Correct Answer: Pituitary Move to reveal answer 17 Sometimes referred to simply as the ‘master gland’ • Adrenocorticotropic hormone • Growth hormone • Luteinising hormone • Thyroid stimulating hormone • Prolactin 18 Sultan Kösen Hormone Characteristics Section 2 of 4 Hormone Transport Receptor • Endocrine – Transported in the blood to the target • Autocrine – Acting on the same cell the hormone was released from • Paracrine – Acting on neighboring cells • Target specificity is driven by target 20 hormonal receptors, which are specific Peptide and Steroid Hormones: Delivery Peptide Hormones • • • • • Steroid Hormones Water soluble Rapid onset of action Short plasma half-life Short duration of action Not orally active Epinephrin pen for treatment of anaphylaxis: • Induces peripheral vasoconstriction • Fast, Injectable • • • • • Poorly water soluble Slow onset of action Long plasma half-life Long duration of action Orally active Thyroxine (T4) tablets: • Oral administration • Treatment of hypothyroidism 21 Peptide and Steroid Hormones: Differences Peptide Hormone Steroid Hormone Highly water soluble Solubility Highly lipid soluble Poorly water soluble Free in the blood Transport Bound to plasma proteins Highly susceptible Protease Degradation Highly resistant Impermeable Membrane Permeability Permeable Extracellular Receptor Site Intracellular* 22 * Exceptions to this rule do exist, and will be discussed as they app When prescribing hormone based drugs it is important to think about routes of administration. Which format is therefore suitable for insulin, a non-steroidal hormone? 1. Food supplement 2. Tablet 3. Injection 4. Capsule Correct Answer: Injection Move to reveal answer 23 Peptide Hormones • • • • • Steroid Hormones Water soluble Rapid onset of action Short plasma half-life Short duration of action Not orally active • • • • • Poorly water soluble Slow onset of action Long plasma half-life Long duration of action Orally active Context & Interest 24 Exemplary Hormonal Mechanisms of Action Section 3 of 4 Key Mechanisms of Action G-Protein Coupled Receptors Receptor Tyrosine Kinases Steroid HormoneReceptor Complexes Hormo neRecept or Comple x 26 G-Protein Coupled Receptors • Transmembrane receptor • G-coupled protein • Intracellular enzyme • Second messenger systems • Intracellular signalling pathways • Immediate cellular effects 27 • Altered gene expression Receptor Tyrosine Kinases • Transmembrane receptor • Autophosphorylation • Adaptor protein • Intracellular signalling pathways • Immediate cellular effects • Altered gene expression 28 Steroid Hormones • Transmembrane receptor • Membrane permeability • Intracellular receptor • Interaction with transcription factors • Altered gene expression 29 Which hormonal mechanism of action classically involves receptor autophosphorylation? 1. 2. 3. 4. Receptor Tyrosine Kinases G-Protein Coupled Receptors Steroid Hormone-Receptor Complexes All of the above Correct Answer: Receptor Tyrosine Kinases Move to reveal answer 30 Receptor Tyrosine Kinases • Transmembrane receptor • Autophosphorylation • Adaptor protein • Intracellular signalling pathways • Immediate cellular effects • Altered gene expression 31 Regulatory feedback loops of the Endocrine System Section 4 of 4 Releasing & Stimulating Hormones Releasing Hormones • Produced by the hypothalamus to induce the release of another hormone Stimulating Hormones (trophic) • Produced by the pituitary, in response to a releasing hormone, to produce a nontrophic hormone • Malfunction at the pituitary is termed secondary endocrine dysfunction Non-trophic Hormone • Considered your effectors, the hormones that drive the action you end up seeing. • Malfunction at the gland itself is33termed Thyrotropin Releasing Hormone (TRH) Thyroid Stimulating Hormone (TSH) T3 + T4 Negative Feedback Loops Circulating Hormone Level • Levels of circulating hormones remain consistent (homeostasis) • High levels inhibit further production • Low levels promote further Hormone production Thyrotrophin Releasing Hormone (TRH) level too high Thyroid Stimulating Hormone (TSH) - Hormone level too Time low 34 T3 + Positive Feedback Loops • Rapid amplification of signal • Driven by changes in the hormonal background • Far less common biologically + Circulating Hormone Level Gonadotropin releasing hormone (GnRH) Luteinising Hormone (LH) 17-β Oestradiol 35 Hormonal Background Changes Hormonal Background Event Time Clinical Relevance of Feedback Loops Understanding the feedback loops allows you to locate the source of the issue Thyrotrophin Releasing Hormone (TRH) Thyroid Stimulating Hormone (TSH) - T3 + 36 Clinical Relevance of Feedback Loops Understanding the feedback loops allows you to locate the source of the issue Thyrotrophin Releasing Hormone (TRH) Very high levels of T3 and T4, but low levels of TRH and TSH - Likely primary endocrine dysfunction - Possible adenoma secreting T3 + T4 Thyroid Stimulating Hormone (TSH) T3 + 37 Clinical Relevance of Feedback Loops Understanding the feedback loops allows you to locate the source of the issue Thyrotrophin Releasing Hormone (TRH) TSH T3 + 38 Very high levels of T3 and T4, but low levels of TRH and TSH - Likely primary endocrine dysfunction -Very Possible T3 high adenoma levels of secreting T3, T4 and + T4 TSH, but low levels of TRH - Likely secondary endocrine dysfunction - Possible adenoma secreting TSH We discussed three different groups of hormones; releasing, stimulating and nontrophic. In which order do these hormones signal? 1. Release -> Stimulating -> Non-trophic 2. Non-trophic -> Stimulating -> Release 3. Release -> Non-trophic -> Stimulating 4. Stimulating -> Release -> Non-trophic Correct Answer: Release -> Stimulating -> Nontrophic Move to reveal answer 39 Releasing Hormone Thyrotropin Releasing Hormone (TRH) Stimulating Hormone Non-trophic Thyroid Stimulating Hormone (TSH) 40 T3 + T4 What you need to know • Understanding of the top-down organisation of the endocrine system • Overview of endocrine organs and their hormones • Major differences between peptide and steroid hormones • The different routes of hormonal transport • Appreciation of the most common hormone-receptor mechanisms • Regulatory feedback loops of the hormone secretion 41 Suggested Additional Reading Greenspan’s Basic and Clinical Endocrinology. “Chapter 1 here provides a good overview of much covered in this lecture, see the other chapters for deeper reading on the different glands discussed.” Tenth Edition. Gardner & Shoback. McGraw-Hill Medical; 2018. ISBN: 978-0071622431. “Similar to above, Chapter 1 provides a slightly different approach if the above is not your style.” Integrated Endocrinology First Edition. Laycock & Meeran. Wiley-Blackwell; 2013. ISBN: 978-0470688120. 42 Feedback Opportunity If you have any feedback for me on this lecture, please either scan the QR code or follow the link below Questionnaire is short (~2 mins) and anonymous All feedback helps me to improve, and as a result improve the quality of your teaching. https://universityofsussex.eu.qualtrics.com/jfe/form/SV_3wVeRAhOFt bXjee 43 Glossary Endocrine – movement of hormones in via the circulatory system to a target receptor in another part of the body Exocrine – secretion of digestive enzymes into the gastrointestinal tract Paracrine – action of hormones onto neighbouring endocrine cells Autocrine - action of hormones onto the cell of origin Homeostasis – the maintenance of physiological equilibrium Primary endocrine disorder – disruption caused by malfunction of the endocrine gland itself Secondary endocrine disorder - disruption caused by malfunction at the pituitary level related to secreting or releasing hormones 44