Endocrine Reg Notes - VETM 5194 - Jan 23 2026 PDF

Welcome to VETM 5194 i Endocrine and Reproductive Systems I: The Healthy Animal Jan. 23 – Feb. 21 General Course Information Maria M. Viveiros Instructor & Course Coordinator [email protected] Contact me with any questions, concerns regarding the course Plea...

Welcome to VETM 5194 i Endocrine and Reproductive Systems I: The Healthy Animal Jan. 23 – Feb. 21 General Course Information Maria M. Viveiros Instructor & Course Coordinator [email protected] Contact me with any questions, concerns regarding the course Please review the syllabus for the class schedule VETM 5194 Class Schedule (posted on eLC) Updated Endocrine System Schedule Reproductive System Schedule | NO changes Assessments | Key Dates NO changes Endocrine System: *Course Activities: 10% of the final grade Quiz #1: 15% (Jan. 29 at 1pm) Exam #1: 25% (Feb. 3 at 10am) Reproductive System *Course Activities: 10% Quiz #2: 15% (Feb. 12 at 1pm) Exam #2: 25% (Feb. 23 at 10am – written: 15%) 1pm – anatomy:10%) *Course activities include all in-class, laboratory, integrative session, online, or take-home activities/assignments Our Team Endocrine System Dr. Viveiros Dr. Fick Dr. Hart Dr. Coleman *Coordinator Reproductive System Dr. Ferrer Dr. De La Fuente Dr. Ellerbrock Micro and Gross Anatomy Dr. Jarrett Dr. Krunkosky Dr. Mohankumar Dr. Norwood Course Learning Objectives By the end of this course, students should be able to …. (1) Identify the major components (gross and microscopic) of the endocrine and reproductive systems. (2) Understand and describe the major physiological functions of the endocrine and reproductive systems in the healthy animal (3) Recognize and discuss how different organ systems interact leading to integrated physiological responses that maintain homeostasis. (4) Apply basic knowledge of normal endocrine and reproductive function to identify examples of basic disruptions that can lead to disease. The Endocrine System (Kidney) Pituitary Ovary Adrenal (Female) Parathyroid Testes (Male) Thyroid Pancreas Viveiros | 2025 Learning Objectives (Endocrine System) To develop a basic understanding of the: Regulation of hormone secretion from endocrine glands & tissues Hormone action on target cells/organs Function of specific endocrine glands Physiopathology upon endocrine disruption ~inappropriate hormone levels ~disrupted response by target cells We’ll begin by reviewing general concepts of endocrine regulation and function … The Endocrine System Essential communication system for Endocrine glands produce and the integration of signals between secrete specific hormones into different organ systems, and critical the circulation and act on key for normal body function. target cells/tissues Consists of specialized key glands (Kidney) Pituitary Ovary Adrenal (Female) Parathyroid Testes (Male) Thyroid Pancreas Endocrine Function Hormone action on target cells/tissues regulates many essential physiological processes 1. Growth and development 2. Cellular metabolism and energy balance 3. Response to stress 4. Maintenance of electrolyte, water and nutrient balance 5. Reproduction Endocrine disruption leads to disorders & disease Insulin dorough Diabetes (Type-I and Type-II) potpond Hyper- and Hypothyroidism tothermore Cushing’s Syndrome cortisol Addison’s Disease cortisol Growth Disorders (Acromegaly, Dwarfism) Reproductive problems: infertility …. Major Endocrine Glands  Pituitary gland  Thyroid gland Pituitary gland  Parathyroid glands Parathyroid gland  Adrenal glands Thyroid gland  Pancreas  Gonads (Ovaries and Testes) (Thymus gland) *Organs also contain endocrine cells Adrenal gland  Adipose Tissue (fat cells) Pancreas  Stomach & small intestines  Heart Ovary (Female)  Kidneys Testis  Liver (Male)  Placenta* Types of Glands Endocrine: Ductless secretion Exocrine: Secretion through of hormones that reach a target a duct to reach target gland or tissue by the blood stream Ex. sweat, mammary and tear glands (…. glands are well vascularized) Hormones Derived from Greek: “Hormao” meaning“Excite/stir up” Chemical messenger Produced by specialized‘effector’cells in endocrine glands or tissue Transported in the circulation Affects a change in the activity of target cells Target Effector Cell Cell Capillary Pancreatic Insulin Many organs Cells (Uptake of Glucose) Three major classes of hormones (1) Protein and Peptide (2) Steroids (3) Tyrosine Derivatives Hormones Hormones (amino acid derivatives) Prohormone Cholesterol Tyrosine Endothelin Steroid Nucleus Epinephrine Thyroxine Insulin Other ‘hormones’ include those derived from: 1. Tryptophan (serotonin and melatonin) 2. Fatty acids (eicosanoids …prostaglandins) 1. Most hormones are amino acid based: Proteins and peptides Water soluble (hydrophilic) Act via membrane-bound receptors Examples: All releasing & inhibiting hormones from the hypothalamus Anterior pituitary hormones (Growth hormone, ACTH, Prolactin, LH, FSH, TSH) Posterior pituitary hormones: (Oxytocin, ADH) Pancreatic hormones: (Insulin, Glucagon) 2. Some hormones are steroids Derived from cholesterol Lipid soluble (Lipophilic) Water insoluble (Hydrophobic) Act via intracellular nuclear receptors Examples: Gonadal hormones Testosterone Estrogen Progesterone Adrenal Cortex Cortisol, Corticosteroids 3. Amino acid derivatives Derived from…. 1. Tyrosine: Thyroid Gland hormones: Thyroxine Adrenal Medulla: Epinephrine 2. Tryptophan GI Tract: Serotonin Pineal gland: Melatonin Water soluble (hydrophilic), but NOT thyroid hormone Hormone Classification Proteins Peptides Steroids Tyrosine derivatives (> 20aa) (< 20aa) Insulin Oxytocin Estradiol Triiodothyronine (T3) Glucagon Vasopressin Testosterone Thyroxine (T4) ACTH Angiotensin Progesterone Epinephrine TSH MSH Cortisol Norepinephrine FSH Somatostatin Aldosterone Dopamine LH Thyrotrophin-RH* Prolactin Gonadotrophin-RH* Growth Hormone Parathyroid Hormone Calcitonin Corticotrophin releasing hormone Growth Hormone releasing hormone *RH: Releasing Hormone aa: amino acid Basic features of hormones …. 1. Synthesis and secretion 2. Transport in the circulation & plasma concentrations 3. Feedback loop regulation 4. Specificity and Mechanism of action on target cells -Hormone receptor types (Cell surface, Intracellular) 5. Action on target cells (1) Synthesis of protein and peptide hormones 1. Transcription of DNA into RNA 2. Excision of sequences (introns) from the initial DNA transcript and modifications of the 3′ and 5′ terminals 1. Transcription 3. Translation of the mRNA into a specific amino acid sequence (the signal sequence is rapidly cleaved) 2. Post-transcriptional modifications 4. Post-translational modifications: the prohormone is normally cleaved into fragments for secretion 3. Translation 4. Post-translational It takes time for cells to produce modifications hormones, so most are stored and released quickly as needed 5. Proteins are processed in the Golgi apparatus of the cell and and packaged into secretory vesicles 6. Proteins are secreted from the cell by regulated exocytosis  Many soluble proteins are continually secreted from the cell by the constitutive secretory pathway, which operates in all cells. This pathway also continually supplies the plasma membrane with newly synthesized lipids and proteins.  Specialized secretory cells have, in addition, a regulated exocytosis pathway, by which selected proteins in the Golgi network are diverted into secretory vesicles, where the proteins are concentrated and stored until an extracellular signal stimulates their secretion. Hormones are released in pulsatile manner Pulsatile release helps to prevent saturation, down regulation of receptor response and desensitization to the hormone Pulsatile Insulin Release in the Dog 1-min sampling 5-min sampling Ex. Response to extracellular Fasting Arterial signaling (Insulin response Portal to glucose) The timing and frequency of Glucose infusion blood sampling in patients is important for accurate diagnosis Time (min) Time (min) Hormone secretion rhythms Types of rhythms (1) Daily Circadian (day/night) Ex. Cortisol, Growth Hormone (GH), Melatonin (2) Monthly or Seasonal Ex. Gonadotropins during reproductive cycles (3) Developmental Ex. puberty, menopause N=Noon Light M=Midnight Dark Ex: Hormone patterns of secretion that regulate female ovarian and uterine cycles Follicular Phase Luteal Phase Menstruation Ovulation Follicular Development LH Progesterone Estrogen Pituitary and ovarian FSH hormone levels Endometrial cycle Days Days Reviewed in the reproduction section (2) Hormone Transport Hydrophobic hormones Hydrophilic hormones Steroids and thyroid hormone Peptides/proteins Bind to transport proteins in blood plasma Mix easily with blood plasma (dissolved) -Increases solubility -Prolongs half-life Diffuse from capillaries to the interstitial fluid and to target cells -Protects against enzyme degradation and kidney filtration Only unbound hormone can leave capillary to reach target cell Transport proteins in blood plasma: Albumin Prealbumin Specific hormone-binding protein (Ex. Thyroxine-Binding Globulin) (3) Hormone secretion is controlled by feedback mechanisms Negative feedback control: Positive feedback control: limits responses amplifies responses -- Endocrine + Endocrine Cell Cell Biological Response Biological Response Hormone Hormone Target Target Cell + Cell + (Ex. Oxytocin secretion during parturition) duringlabor (A) Feedback control via the HPA The activity of the Hypothalamic-Pituitary Axis thyroid gland, adrenal cortex and Hypothalamus gonads is controlled by Short-loop the feedback effects of feedback Neurohormone their circulating signal hormones on the Pituitary Gland Hypothalamic-Pituitary GH - PRL Long-loop Axis (HPA) feedback Trophic signal hormone GLAND GH: Growth Hormone Adrenal cortex PRL: Prolactin Thyroid, Gonads Thyroid hormones, Steroids Example 1: Regulation of Thyroid Hormone (HPA) (T3 and T4) Secretion Reviewed by Dr. Fick Dopamine, IGF-1, Starvation Hypothalamus Cold exposure Thyrotropin Releasing Hormone (TRH) Negative Feedback Anterior Pituitary Gland Thyroid Stimulating Hormone (TSH) Thyroid gland 1. Increased Metabolism Thyroid Hormone 2. Growth and Development (T4) and T3 Example 2: Regulation of Cortisol Release (HPA) from the Adrenal Cortex Reviewed by Dr. Hart Cortisol Function: response to stress Increased Metabolism (proteins, fats & carbohydrates) -Protein breakdown -Lipolysis -Gluconeogenesis Maintains glucose levels Anti-inflammatory, Suppress immune response Growth & Development Example 3: Gonadotropin (FSH and LH) Function Reviewed in the reproduction section Females Males FSH ….stimulates FSH: Ovarian follicle development Spermatogenesis Inhibin/activin production Inhibin production Steroid hormone production Androgen binding protein production LH: LH: Oocyte ovulation Testosterone production Corpus luteum (CL) development Progesterone production (B) Feedback control: NOT via the HPA The secretory activity of glands not under direct control of the hypothalamic-pituitary axis -Endocrine pancreas -Parathyroid glands Controlled by feedback signals from the variable they regulate: -blood glucose (pancreas) -calcium (parathyroid) Feedback GLAND signal Pancreas, Parathyroid Blood Glucose Calcium Ex.1: Blood glucose regulation of insulin secretion by pancreatic -cells Reviewed by Dr. Fick Ex. 2: Parathyroid Regulation of Plasma Ca2+ Reviewed by Dr. Viveiros How do hormones promote specific cellular responses in different tissues? Topic Outline (1) Hormone interaction with target cells Specific hormone receptor types (2) Cellular response to hormone stimulation (3) Hormone inactivation and clearance (4) Endocrine Disruption (1) Hormone specificity & mechanism of action …is dependent on interaction with specific receptors on target cells A hormone is transported ‘everywhere’ via the circulation Only those cells that express specific hormone receptors can respond (target cells) to hormones Each target cell may express several receptor types Hormone Receptors Hormone receptors are proteins or glycoproteins -Binding domain -Signal transducing domain Recognize and bind specific hormones (ligand). Each hormone binds to a unique receptor Undergo a conformational change when bound to a hormone Transduce a signal (catalyze biochemical reaction or alter the activity of adjacent molecules) that promotes a cellular response Hormone Receptor Types: (1) Membrane bound (2) Intracellular Hydrophilic Hormones Hydrophobic Hormones Water soluble Lipid soluble Proteins and peptides Steroids and thyroid Do not enter the cell hormone Bind to membrane-bound Enter the cell receptors Bind specific cytoplasmic or nuclear receptors Cell membrane Mechanisms of protein hormone action Peptides and proteins interact with membrane receptors Two main classes of protein hormone receptors G-protein linked receptors activate serine/threonine kinases through second messengers such as cAMP, diacylglycerol, calmodulin Receptors with inherent tyrosine kinase activity or associated with intracellular molecules possessing tyrosine kinase activity Hormone receptor binding activates (complex) intracellular signaling pathways that promote cellular responses …just remember A, B, C G-protein linked receptor Tyrosine Kinase Receptor (A) Hormone-receptor binding (B) Activation of intracellular signaling pathways (C) Can lead to activation of: (1) Existing proteins (ex. by phosphorylation with different kinases) OR (2) Transcriptional factors, which leads to gene activation and formation of new proteins to promote a cellular response Example: Insulin Receptor 1 Transmembrane receptor 2 Belongs to the large class of tyrosine kinase receptors Consists of two alpha subunits and two beta subunits Insulin binding promotes receptor 3 dimerization & activation of kinase domain, which in turn phosphorylates intracellular protein kinases Cell response: increased expression of glucose transporter (GLUT4) on cell membrane 4  glucose uptake by the cell Mechanisms of steroid hormone action Steroids interact with cytoplasmic or nuclear receptors Receptor binding to DNA regulatory site promotes gene activation (genomic action) Leads to protein synthesis New proteins promote one or more cellular responses Steroid hormone receptor binding (A) Steroid hormone binding to its receptor leads to ….. (B) Receptor dimerization and binding to specific DNA regulatory elements Éf É ÉI (C) Gene activation and protein synthesis ….to promote a cellular response Nuclear receptor structure Transcription DNA Hormone Regulation Binding Binding Domain Domain Domain Summary: target cell hormone response The same hormone can promote different cellular responses in different target cell types Specificity is controlled by the: (i) receptor and its (ii) second messenger activation within the cell Ex. Cortisol induces different physiological responses in distinct target cell types Reviewed by Dr. Hart Cortisol Function: response to stress Increased Metabolism (proteins, fats & carbohydrates) -Protein breakdown -Lipolysis -Gluconeogenesis Maintains glucose levels Anti-inflammatory, Suppress immune response Growth & Development Different levels of hormone action WHOLE BODY LEVEL Regulation and integration of: Ionic and fluid balance energy balance (metabolism) coping with the environment growth and development reproduction MOLECULAR LEVEL Hormone CELLULAR LEVEL Regulation of: Actions Regulation of: Gene transcription Cell division protein synthesis differentiation and degradation death (apoptosis) enzyme activity motility protein conformation & secretion protein-protein interaction nutrient uptake (2) Receptor response to hormone stimulation Priming effect (upregulation of receptors) Hormone induces more of its own receptors in target cells Results in greater response in target cell Desensitization (downregulation of receptors) Constant exposure to a hormone attenuates the cell response  in receptor numbers on targets (endocytosis) Attenuation of secondary messenger signaling No. Receptors Concentration (M) Reduced by 33% Hormone Pulsatile mode of hormone secretion helps to prevent 0 desensitization 10-11 10-10 10-9 Specific hormone binding (3) Hormone Inactivation Once a hormone exerts its function it must be inactivated Inactivation is the metabolic conversion of a biologically active hormone into an inactive one (enzymatic degradation) 1. Peripheral inactivation Degradation in blood or intracellular spaces The liver or the kidneys 2. Inactivation in target tissues After the hormone has triggered a cellular response Inactivation may involve Complete metabolism of the hormone (..no byproduct in the urine) Hormone modification such as the addition of methyl groups or glucoronic acid (..degradation product in the urine can be measured as a crude index of the rate of production) Hormone clearance and excretion Clearance: The rate of hormone disappearance from plasma Metabolic Clearance Rate (MCR) The volume of plasma cleared of the hormone per unit time Inversely related to hormone half-life (the shorter the half-life, the greater the MCR) Half-life: Time for the hormone concentration in plasma to decrease by half Ranges vary because of differing secretion and excretion rates -Most peptide hormones: minutes ~ hours -Steroid & Thyroid hormones: Days ~ weeks Excretion (Elimination) Excreted by the liver into the bile Steroid hormones & thyroid hormone Long-half life due to binding to plasma proteins Excreted by the kidneys Amino acid-based hormones (short-half life) Knowing the time course of hormone stability in blood, as well as the onset and duration of its action is important … when you administer a hormone therapeutically it’s important to know -the blood plasma concentration -how soon it will act -how sustained the response will be (… half life, inactivation/clearance) (4) Endocrine disruption 1. Hormone Excess (hyper-function) Hyperplasia of a gland Hormone producing tumors in endocrine gland (eg. Pituitary) Excessive stimulation of a gland Graves’ Disease: The thyroid is stimulated by antibodies that mimic the hormone (TSH) 2. Hormone Deficiency (hypo-function) Congenital defects of endocrine gland/tissue Destruction of a endocrine tissue due to ischemia, inflammation, autoimmune responses, etc Inactive hormones -Some glands may produce biologically inactive hormones -Active hormones may be destroyed by circulating antibodies (4) Endocrine disruption 3. Altered Responsiveness of Receptors Decreased or lack of response to a hormone -Reduced or no receptor expression in the cell -Defects in receptor structure that limit hormone recognition or binding Excessive response to a hormone -Lack of receptor down-regulation -Constitutive receptor activation Example of an endocrine disorder in which there is a problem with hormone levels vs. hormone response: Type I diabetes: -“insulin dependent” diabetes - juvenile onset - disruption in hormone synthesis/release - possible autoimmunity Type II diabetes: -“insulin resistance” - adult onset … but increasing rates in children - poor/limited response to insulin (..low sensitivity to insulin) Learning objectives Explain hormone type, secretion and transport Know the major endocrine glands Explain feedback control of hormone secretion Classify hormones according to chemical structure and describe implications of structure Explain how the same hormone can promote different responses in various cells types Understand membrane bound vs. intracellular hormone receptors and signaling. Know the key differences. Know the various mechanisms by which endocrine disruption can occur (..disruption of hormone secretion or response to hormone stimulation