Physiology of the Endocrine System Lecture PDF

Physiology of the Endocrine System: Introduction Block 3 Prof Joji Mercier Room 2-1.6, Department of Physiology NS-1 Building, Hatfield Campus Tel: 012 319 2141 The endocrine system Communication between cells, tissues and organs Control mechanisms for optimal functioning In conj...

Physiology of the Endocrine System: Introduction Block 3 Prof Joji Mercier Room 2-1.6, Department of Physiology NS-1 Building, Hatfield Campus Tel: 012 319 2141 The endocrine system Communication between cells, tissues and organs Control mechanisms for optimal functioning In conjunction with the nervous system Responsible for the regulation of a wide range of functions: ▪ Growth ▪ Development ▪ Reproduction ▪ Homeostasis ▪ response to external stimuli and stress Failures in these communication channels are common ▪ diseases of the endocrine system Prof Mercier Block 3: Introduction to the endocrine system  Important endocrine glands and their locations in the body The endocrine system includes several ductless glands or groups of cells which produce and secrete hormones Endocrine glands Also by: Isolated endocrine cells: ▪ Diffuse endocrine system Neurons ▪ Neurohormones Cells of the immune system ▪ Cytokines Ectohormones ▪ Pheromones neuroepithelial bodies in the bronchopulmonary tree Prof Mercier Block 3: Introduction to the endocrine system Hormones Many organs in the body secrete hormones ▪ Biologically active compounds ▪ Exert a biological effect ▪ Released by endocrine cells into the extracellular fluid then which controls/helps control functions of cells ▪ Hormones may be classified on where they act: ▪ Paracrine hormones: made and act locally affect the tissue that synthesizes the hormone ▪ Autocrine hormones: act on the cell that synthesized them or on neighbouring cells of the same type ▪ General endocrine hormones: transported via the bloodstream to other tissues or organs All hormones act by binding to specific receptors ▪ on the cell surface OR within the target cell hormone-receptor interaction triggers and coordinates a wide range of biological effects. Prof Mercier Block 3: Introduction to the endocrine system Hormones cont… Negative feedback regulation is important for homeostatic control ▪ the final output of hormone action involves a complex feedback loop that regulates either further hormone synthesis or secretion, or hormone sensitivity Several hormones may control one process, or one hormone may control several processes ▪ The endocrine system is not compartmentalized ▪ eg at least four different hormones are involved in the regulation of [p-glucose] ▪ Conversely, single hormones such as testosterone influence a range of metabolic processes Synthesised & stored vs synth on demand Different actions when secreted at different locations ▪ Eg CCK Candidate hormones: Cytokines, Growth factors, Releasing and inhibiting factors Prof Mercier Block 3: Introduction to the endocrine system Basic endocrine concepts Neural/chemical/external stimulus Endocrine organ Hormone synthesis and secretion feedback Negative Hormone Peripheral circulation Target organ Receptor binding and hormone action Biochemical/ physiological effect Prof Mercier Block 3: Introduction to the endocrine system Hormonal effects Hormones interact with their target cells to cause: ▪ Synergism ▪ Permissiveness ▪ Antagonism Synergism ▪ The effect of interacting hormones is more than additive ▪ The combined effect is greater than the sum of individual Potentiation ▪ e.g. glucagon, cortisol, adrenalin in ↑ HGT Permissiveness ▪ One hormone cannot excerpt full effect without a second present e.g. gonadotropins, steroid hormones and thyroxin Antagonism ▪ 2 molecules oppose each other Competitive inhibition – same receptor (chemo) Functional antagonism – different metabolic pathways/receptor production Glucagon & GH antagonise insulin Prof Mercier Block 3: Introduction to the endocrine system Types of hormones May be simple or complex Different chemical structures Many different types of molecules function as hormones ▪ modified amino acids Adrenaline ▪ Polypeptides synthesized on the ribosome vary in size from a tripeptide ( TRH) up to complex glycoproteins (LH) smaller peptide hormones are synthesized as larger polypeptides or protein pre- or pro- hormones cleaved by specific proteolytic enzymes to release the active ▪ modification of simple lipids such as cholesterol or fatty acids Some require further metabolism within their target cell before they can exert their full biological effect testosterone dihydrotestosterone T4 T3 Prof Mercier Block 3: Introduction to the endocrine system Hormones Prof Mercier Block 3: Introduction to the endocrine system Chemical derivation of hormones Prof Mercier Block 3: Introduction to the endocrine system Steroid hormones Prof Mercier Block 3: Introduction to the endocrine system Peptide hormones Prof Mercier Block 3: Introduction to the endocrine system Comparison of hormone types Prof Mercier Block 3: Introduction to the endocrine system Circulation, action, and inactivation of hormones Small or hydrophobic hormones are transported bound to carrier proteins ▪ albumin ▪ specific plasma binding globulins thyroxine and cortisol are transported on thyroid-binding globulin (TBG) and cortisol-binding globulins (CBG) ▪ transport proteins extend the half-life May be inactivate until reached target: ▪ bound portion inactive, free portion active. Also allows dynamic regulation of active portion Increase the plasma concentration of the smaller hormones ▪ Eliminated rapidly in the liver or kidney The clearance rate of different hormones varies enormously ▪ a few minutes (insulin) ▪ hours (steroids) ▪ days (thyroxine) At the cellular level, hormones exert their actions through a wide range of signal transduction mechanisms Hormone inactivation occurs by further metabolism ▪ proteolysis, hydroxylation, and conjugation ▪ followed by excretion of the metabolites Prof Mercier Block 3: Introduction to the endocrine system  HORMONE RECEPTORS Hormones are biochemical messengers that act to orchestrate the responses of different cells within a multi-cellular organism They are generally synthesized by specific tissues and secreted directly into the blood, which transports them to their target-responsive organs Hormones can broadly be subdivided into two major classes ▪ steroid hormones ▪ polypeptide hormones achieve their biological effects by interacting with specific receptors to induce intracellular signalling cascades Receptors can be up-regulated or down0regulated to control hormone activity Prof Mercier Block 3: Introduction to the endocrine system Intracellular receptors: steroid hormone receptors Steroid hormones traverse cell membranes ▪ cholesterol-based structure ▪ Cortisol, sex hormones, vitamin D Initiate their responses via cytoplasmic-located steroid hormone receptors ▪ Genomic effect Some also have rapid non-genomic effect Belong intracellular receptor superfamily, which also transduces signals from other small hydrophobic signalling molecules ▪ thyroxine and vitamin A-derived retinoids Prof Mercier Block 3: Introduction to the endocrine system Intracellular R are transcription factors Intracellular hormones/receptor complexes: ▪ bind to regulatory regions of DNA of genes that are responsive to the particular hormone ▪ ‘Ligand binding' (ligation) induces a conformational change in the transcription factor that allows it to activate, or repress, gene induction Target cells have specific receptors for the individual hormones But have distinct combinations of cell-type-specific regulatory proteins that work with the intracellular hormone R Precise repertoire of genes that are induced Hormones induce distinct sets of responses in different target cells Prof Mercier Block 3: Introduction to the endocrine system Steroid hormone mode of action Prof Mercier Block 3: Introduction to the endocrine system Cell-surface receptors: polypeptide hormone receptors Polypeptide hormones act through membrane receptors ▪ cannot cross cell membranes ▪ Initiate their effects on their target cells via specific cell surface receptors ▪ transmembrane signal transduction initiates an intracellular signal cascade that directs a specific cell function Hormones = 'first messengers' (they do not enter the target cell ) intracellular effects mediated by low-molecular-weight signaling molecules ‘Second messengers’ then activate specific enzymes (often a protein kinase) ▪ cyclic adenosine monophosphate (cAMP) or cGMP (inactivated by phosphodiesterase) ▪ Calcium Many families of hormones, growth factors, and cytokines  Cellular mechanisms of peptide hormone action Signal cascade induces amplification of hormone signal Prof Mercier Block 3: Introduction to the endocrine system Synthesis of hormones Basic units from the bloodstream Usually, only small amounts of hormones are made in advance ▪ Steroid hormones are mostly only produced when needed Peptide hormones can be stored in secretory vesicles in the endocrine cells ▪ Released by exocytosis Post-translational modification ▪ Preprohormone → prohormones → active hormone Prof Mercier Block 3: Introduction to the endocrine system Post-translational modification of hormones Prof Mercier Block 3: Introduction to the endocrine system Post translational processing of TRH Prof Mercier Block 3: Introduction to the endocrine system POMC Prof Mercier Block 3: Introduction to the endocrine system Post-translational modification of insulin Prof Mercier Block 3: Introduction to the endocrine system Control of the production and secretion of hormones The hypothalamus together with the pituitary gland plays a major role in controlling the production and secretion of hormones by endocrine glands Control of a hormone can occur in 3 different ways: 1. Negative feedback: a high concentration of the hormone or the substance it induces release of in the blood suppresses the production of the same hormone. Eg T4, ACTH, E 2. Specific components: the level of a specific substance in the plasma controls the secretion of hormones which is involved in its metabolism (glucose for insulin, calcium for PTH, sodium for aldosterone etc) ▪ Reflex pathways 3. Sympathetic nervous system e.g. adrenalin Prof Mercier Block 3: Introduction to the endocrine system Reflex/short feedback loop Regulatory Eg: calcitonin hormone 1 Insulin Endocrine Eg: Ca2+ parameter Glucose Eg: PTH Regulatory Glucagon, (GH, cortisol, hormone 2 catecholamines) Prof Mercier Block 3: Introduction to the endocrine system Reflex control: Glucose Prof Mercier Block 3: Introduction to the endocrine system Reflex control: Ca Prof Mercier Block 3: Introduction to the endocrine system Negative feedback loops in the HP pathway Prof Mercier Block 3: Introduction to the endocrine system Endocrine integration with the nervous system Emotional aspects Overlap eg insulin and ANS Stimuli integrated by CNS ▪ Effects via efferent neurons Neurohormones ▪ Specialized groups of neurons ▪ 3 groups Catecholamine secreted by modified neurons in the adrenal medulla Hypothalamic neurohormones secreted by post-pituitary Hypothalamic neurohormones controlling ant-pituitary Endocrine structures in the brain ▪ Pineal gland ▪ Pituitary gland Prof Mercier Block 3: Introduction to the endocrine system HORMONE MEASUREMENT A MATTER OF TIMING involved with homeostatic mechanisms secretion is not constant most hormones are released in bursts in response to a specific stimulus single spikes (e.g. growth hormone, GH) sustained release (e.g. insulin) Strict biological rhythms, which may be at intervals of ▪ 1-2 hours (LH) ▪ 24 hours (cortisol) ▪ 28 days (progesterone) Always standardize the time and status of the patient before sampling Free vs total Often necessary to perform multiple sampling or dynamic testing Prof Mercier Block 3: Introduction to the endocrine system  Considerations of hormone measurement Prof Mercier Block 3: Introduction to the endocrine system Study tips NB: understand each word and concept – look it up to understand There can be many words for the same thing: Eg: adrenalin = epinephrin pituitary = hypophysis etc Know the rules…and then the exceptions Eg: Thyroxin is a peptide hormone that acts like a steroid hormone GH is a tropic hormone (causes the release of somatomedin IGF) as well as a direct-acting endocrine hormone Be careful of abbreviations ▪ Eg: TSH is not the same as TRH ▪ Define all abbreviations you use in assessments for full marks Read the textbook and make your own spider diagram summaries Please note – these slides are lecture aids and NOT primary study material Prof Mercier Block 3: Introduction to the endocrine system References 1. L Sherwood. Human Physiology: From cells to systems. 2016 2. Baynes & Dominikzac. Medical Biochemistry 2nd ed. Please note: distribution of this presentation is in contravention of the copyright act, as well as the agreements between the University of Pretoria and the resources used. Prof Mercier Block 3: Introduction to the endocrine system