Endocrinology - Intro 2024 PDF

Endocrinology - INTRO VP 2024 Clara Camargo, DVM 1. Understand the physiological relevance of hormonal regulation in homeostasis 2. Define classical and non-classical endocrine glands and list some examples 3. Differentiate the types of chemical messengers 4. Differentiate the chemical structure of...

Endocrinology - INTRO VP 2024 Clara Camargo, DVM 1. Understand the physiological relevance of hormonal regulation in homeostasis 2. Define classical and non-classical endocrine glands and list some examples 3. Differentiate the types of chemical messengers 4. Differentiate the chemical structure of hormones and describe their characteristics 5. Understand hormone-receptor interactions THE ENDOCRINE SYSTEM Definition: Integrated network of multiple glands and organs derived from different embryologic origins that release hormones (small peptides, glycoproteins, lipid derived). Coordinate and integrate cellular activity within the whole body:  Digestion  Reproduction  Electrolyte and fluid balance  Energy balance  Fuel mobilization  Growth, development & senescence  Response to injury  Mood  Stress Hormones will signal neighboring or distant target cells THE ENDOCRINE SYSTEM – general concepts The endocrine system has evolved to allow physiological processes to be coordinated and regulated.  The system uses chemical messengers called hormones One of the important characteristics of the endocrine system is the amplification of the signal  One hormone molecule can activate the formation of many messenger molecules, and each of these can induce the formation of many enzyme molecules (response) THE ENDOCRINE SYSTEM – general concepts Works closely with CNS/PNS & Immune System  Neuroendocrine Integrated nervous & endocrine systems 3 core components of the endocrine system  Endocrine glands  Hormones  Target organ HYPOTHALAMUS GHRH, CRH, TRH, GnRH, PRH Somatostatin Dopamine Pituitary gland ADENOHYPOPHYSIS GH THYROID ACTH T3 MSH T4 TSH Calcitonin FSH LH Prolactin NEUROHYPOPHYSIS Vasopressin/ADH Oxytocin PINEAL Melatonin PARATHYROID PTH ADRENAL GLANDS Aldosterone Cortisol Androgens Catecholamines OVARIES Estrogens Progesterone TESTICLES Testosterone PANCREAS Insulin Glucagon Somatostatin NON-CLASSICAL ENDOCRINE GLANDS HEART Atrial Natriuretic Peptide INTESTINES KIDNEY 1,25Dihydroxicholecalciferol Erythropoietin Cholecystokinin Gastrin Secretin Vasoactive Intestinal peptide Somatostatin Motilin Gastric Inhibitor peptide Neurotensin PLACENTA Gonadotropin Estrogens Androgens Inhibin Relaxin ADIPOSE TISSUE Leptin Adiponectin Resistin CLASSICAL HORMONE DEFINITION  Chemical substances produced and secreted by specialized endocrine glands/cells in minute quantities (very low concentrations), transported by the vascular system or interstitial fluid affecting target cells/tissues.  Hormones can be synthesized and released from: classical endocrine tissue/gland non-classical endocrine tissue/glands and other organs  Can act: Locally Distant target cell Some signaling molecules can also act as hormones  i.e., some neurotransmitters such as dopamine can be considered hormones when secreted by the hypothalamus GENERAL PROPERTIES OF HORMONES  Bind to specific receptors  Slow onset of action (few hours to days) → action on the genetic machinery to initiate transcription of genes  Absence of enzymatic activity → cannot catalyze any intracellular enzymatic reaction directly  Signal transduction → activation of a cascade of intracellular signaling (first messenger)  Feedback mechanism regulation (negative and positive)  Metabolic clearance rate → after eliciting desired biological effects, they are rendered inactive by the target tissue and/or eliminated from the circulation by liver and kidneys Textbook of Veterinary Physiology 1Ed Pradip Kumar Das, Dipak Banerjee CHEMICAL MESSENGER CLASSIFICATION Textbook of Veterinary Physiology 1Ed Pradip Kumar Das, Dipak Banerjee CHEMICAL MESSENGER CLASSIFICATION Neuroendocrine hormones (neurohormone) Are secreted by neuroendocrine tissue due to neuronal stimulation into the bloodstream Target cells in different organs or tissues (at another location in the body)  I.e., ADH (vasopressin) and oxytocin produced by the hypothalamus and secreted by the posterior pituitary) Endocrine hormones Synthesized and released by glands or specialized cells into the bloodstream Target cells at another location in the body  I.e., Insulin - Beta cell of the Pancreas,  I.e., Cortisol - Adrenal Cortex of the Adrenal Gland CHEMICAL MESSENGER CLASSIFICATIONS Paracrine hormones Are secreted by cells into the ECF and affect neighboring target cells of a different type  Fibroblast growth factor Autocrine hormones autocrine paracrine endocrine Are secreted by cells into the ECF and affect the function of the same cells that produce them  Ex: IL-6 in cancer cells; IL-1 in monocytes CHEMICAL MESSENGER CLASSIFICATION Neurotransmitters Released by axon terminals, act on nearby cells → communication between neurons, or between neurons and target cells (i.e., skeletal muscle fibre) Signals are limited in the distance traveled and the area of the cell influenced (synaptic cleft, neuromuscular junction…)  I.e., Acetylcholine, epinephrine Cytokines Secreted by immune cells into the extracellular fluid (interstitial fluid or blood) and can function as autocrine, paracrine or endocrine signal molecules Act as immunomodulators  Ex: Interleukins are released from T helper cells and act on other immune cells  Leptin is a cytokine produced by adipocytes (participate in inflammatory responses), it can also act as hormone supressing hunger autocrine paracrine endocrine CHEMICAL STRUCTURE OF HORMONES PROTEIN and PEPTIDE HORMONES INSULIN SYNTHESIS Comprises the majority of hormones  Insulin, ACTH, PTH, CCK  LH, FSH and TSH (glycoproteins) Usually synthesized as:  inactive molecule in the ER (pre-prohormone)  cleaved in the Golgi apparatus (prohormone → hormone)  packaged into secretory granules awaiting for secretion PRE-PROHORMONE → PROHORMONE → HORMONE CHEMICAL STRUCURE OF HORMONES PROTEIN AND PEPTIDE HORMONES  Circulate unbound in the blood FIG. 33.3 Subcellular components of peptide hormone synthesis and secretion. RER, Rough endoplasmic reticulum. (From Hedge GA, Colby HD, Goodman RL. Clinical Endocrine Physiology. Philadelphia: Saunders; 1987.)  HYDROPHILIC  Mostly short half-life (at most 30 minutes)  Bind to receptors in the cell membrane  Hormone-receptor complex activate signal transduction (i.e., GPCRs, RTK) CHEMICAL STRUCTURE OF HORMONES AMINES (hormones derived from the modification of amino acids)  Hydrophilic (except thyroid hormones = hydrophobic)  I.e., derived from the amino acid tyrosine  T3, T4 (thyroid hormones)  Catecholamines (dopamine, NE, Epinephrine)  Half-life depends on the hormone Epinephrine = 1 minute Thyroxine = 7-10 days  Circulate unbound in the blood  Except T3 and T4 → require carrier proteins  Can bind to (Thyroxine-binding globulin (TBG) and Albumin both  cell membrane receptors carrier proteins produced by the liver)  nuclear receptors CHEMICAL STRUCURE OF HORMONES STEROID HORMONES Hormones derived from CHOLESTEROL  Adrenocortical hormones (glucocorticoids and mineralocorticoids)  Sex hormones (estrogens, progesterone, androgens) Cells producing steroid hormones have abundance of:  Lipid droplets containing cholesterol esters (CE)  Mitochondria & Smooth endoplasmic reticulum (SER) SER MIT CHEMICAL STRUCURE OF HORMONES STEROID HORMONES The type of steroid hormone that is synthesized depends on the presence of specific enzymes within the cell.  Sex steroid–forming cells (testicles, ovaries) do not have enzymes that allow the formation of adrenocortical hormones  The adrenal cortex contains the enzyme systems necessary for the formation of both adrenocortical hormones and sex hormones FYI CHEMICAL STRUCURE OF HORMONES STEROID HORMONES There is no storage of steroid hormones within the cell They are secreted immediately after synthesis by simple diffusion across the cell membrane because of their lipophilic structure Synthesis and secretion of steroid hormones occur in a tightly coupled manner, whereby the rate of hormone secretion is controlled by the rate of synthesis The only storage form of steroids within these cells → the precursor molecule cholesterol ester Steroids metabolic clearance rates are usually constant  Concentration of steroids in plasma is usually a good reflection of the secretion rate HORMONE - RECEPTOR INTERACTION  Protein Hormones have specific receptors on target tissue plasma membranes (i.e., GPCRs, RTK)  Steroids have specific intracellular receptors (cytoplasm or nucleus) Specificity and affinity of receptor and hormone allow hormones to be in low concentration in the blood but effective in producing significant tissue response Termination of the action of a hormone:  Metabolization (tissue-specific degradation, liver, kidneys)  Dissociation of the hormone from the receptor → ↓ in plasma concentrations of the hormone  Internalization of the receptor-hormone complex through the process of endocytosis (desensitization) HORMONE - RECEPTOR INTERACTION Down regulation Down-regulation is a mechanism in which a hormone decreases the number or affinity of its receptors in a target tissue May occur by: decreasing the synthesis of new receptors increasing the degradation of existing receptors inactivating receptors  The purpose of down-regulation is to reduce the sensitivity of the target tissue when hormone levels are high for an extended period Up regulation Down-regulation is a mechanism in which a hormone increases the number or affinity of its receptors in a target tissue. May occur by: increasing the synthesis of new receptors decreasing the degradation of existing receptors activating receptors  A hormone also can up-regulate the receptors for other hormones. I.e., estrogen can up-regulate its receptors in the uterus and up-regulate the receptors for LH in the ovaries