PSC322_Physio_Patho_Lec_16_Endocrine system_Feb-16-2024r (1).pptx

PSC322; Physiology/Pathophysiology Friday, Feb 16th 2024 Introduction to Endocrine System & Endocrine Function: General Principles Insong James Lee, Ph.D. Office: BRB, Room 110 Office hours: Generally, from noon to 5:00 PM during the week or by appointment Office tel: 518-694-7265 E-mail: Insong.Lee...

PSC322; Physiology/Pathophysiology Friday, Feb 16th 2024 Introduction to Endocrine System & Endocrine Function: General Principles Insong James Lee, Ph.D. Office: BRB, Room 110 Office hours: Generally, from noon to 5:00 PM during the week or by appointment Office tel: 518-694-7265 E-mail: [email protected] Department of Pharmaceutical Sciences Albany School of Pharmacy and Health Sciences Bioscience Research Building (BRB), room 110 9 Samaritan Rd Albany, NY 12208 Friday, Feb 16th 2024 Introduction to Endocrine System & Endocrine Function: General Principles Learning objectives: Define the following terms: endocrine, autocrine and paracrine hormones. Compare/Contrast peptide and steroid hormones in terms of synthesis, release, transport in plasma, receptor stimulation, and cellular effects. Explain the principle of negative and positive feedback in hormone release. Corresponding textbook reading (Access Pharmacy): Ganong's Review of Medical Physiology, Section 3, Chapters 16-18 PSC322; Physiology/Pathophysiology Introduction to Endocrine System & Endocrine Function: General Principles Topic I. II. III. IV. V. Overview of the endocrine system. Overview of hormones. Regulation of hormone release. Feedback mechanisms. Mechanism of hormone action. slides 4-6 7-11 12-19 20-27 28-34 Overview of Endocrine System To maintain homeostasis, our body’s various parts and organs must communicate with each other. Two systems help ensure communication: the endocrine system and the nervous system. The endocrine system, which relies on the production and release of hormones from various glands and on the transport of those hormones via the bloodstream, is better suited for situations that require more widespread and longer lasting regulatory actions. Conversely, the nervous system generally allows rapid transmission (i.e., within fractions of seconds) of information between different body regions. Thus, the two communication systems complement each other. In addition, the two systems interact: Stimuli from the nervous system can influence the release of certain hormones and vice versa. Endocrine System: Overview The glands and organs that make hormones and release them directly into the blood so they can travel to tissues and organs throughout the body Acts with the nervous system to coordinate and integrate the activity of body cells Influences metabolic activities by means of hormones transported in the blood Responses occur more slowly but tend to last longer than those of the nervous system Controls and integrates Reproduction Growth and development Maintenance of electrolyte, water, and nutrient balance of blood Regulation of cellular metabolism and energy balance Mobilization of body defenses Key Endocrine System Components Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Ovary (female) Testis (male) Other tissues and organs that produce hormones: adipose cells, cells in walls of the small intestine, stomach, kidneys, heart Chemical Messengers Hormones: any of various internally secreted compounds, as insulin or thyroxine, formed in endocrine glands or tissues, that affect the functions of specifically receptive organs or tissues when transported to them by the blood (for endocrine): Autocrines: chemicals that exert effects on the same cells that secrete them Paracrines: locally acting chemicals that affect cells other than those that secrete them Autocrines and paracrines are local chemical messengers and will not be considered part of the endocrine system Classes of Hormone Three main classes: 1. Amino acid-based hormones, amino acid derivatives 2. Peptides, proteins, multiple amino acids 3. Steroid or lipid based, synthesized from cholesterol or arachidonic acid Tyrosine is hydroxylated and decarboxylated to form norepinephrine Three Major Types of Hormones or Lipid based or arachidonic acid or tryptophan Thyroxin and triiodothyronine are thyroid hormones made up of tyrosine amino acids Three Major Types and Subtypes of Hormones , estrogen Nitric oxide is a vasodilator; it relaxes the smooth muscles of the blood vessels, causing vasodilation. Thus, nitric oxide increases blood flow and lowers blood pressure. Nitric oxide is a free radical: it has an unpaired electron Regulation of Hormone Release slides 13-18 Control of Hormone Release Hormones are synthesized and released in response to: 1. Humoral stimuli-relating to the body fluid 2. Neural stimuli 3. Hormonal stimuli Blood levels of hormones are controlled by mostly by negative feedback systems Vary only within a narrow desirable range Humoral Stimuli Changing blood levels of ions and nutrients directly stimulates secretion of hormones Examples: Humoral Stimuli Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca2+ concentrations to rise and the stimulus is removed CaSR: calciumsensing receptor (a) Humoral Stimulus Binding of Ca++ to CaSR 1 Capillary blood contains low concentration of Ca2+, which stimulates… Gαq/11 Capillary (low Ca2+ in blood) Thyroid gland Parathyroid (posterior view) glands Inhibition parathyroid chief cells In the parathyroid gland, activation of CaSR by binding of Ca ++ induces Gαq/11-mediated activation of phospholipase C (PLC), increases inositol 1,4,5-trisphospate (IP3) and leads to intracellular Ca2+ mobilization, which acts as a secondary messenger. Cytoplasmic Ca2+ inhibits cAMP production both directly by downregulating adenylyl cyclase (AC) and indirectly via prostaglandins, leading to suppression of PTH synthesis from the parathyroid chief cells. In conditions of blood Ca2+ depletion, the CaSR remains inactivated and no suppression of PTH occurs, thus promoting PTH synthesis and secretion. In the kidneys, CaSR activation leads to a decrease in Ca2+ reabsorption PTH Parathyroid glands 2 …secretion of parathyroid hormone (PTH) by parathyroid glands* Neural Stimuli Nerve fibers stimulate hormone release – Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines (b) Neural Stimulus 1 Preganglionic sympathetic fibers stimulate adrenal medulla cells… CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary 2 …to secrete catechola- mines (epinephrine and norepinephrine) Nervous System Modulation of Endocrine System The nervous system modifies the activity of endocrine tissues and their negative feedback mechanisms – Example: The level of glucose regulates the activity of hypothalamic neurons and they signal to the brainstem which innervates the pancreas – Insulin and glucagon secretion is modulated by the nerve signals from the brainstem Hormonal Stimuli Hormones stimulate other endocrine organs to release their hormones – Hypothalamic hormones stimulate the release of most anterior pituitary hormones – Anterior pituitary hormones stimulate targets to secrete still more hormones – Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from the final target organs inhibit the release of the anterior pituitary hormones (c) Hormonal Stimulus 1 The hypothalamus secretes hormones that… Hypothalamus 2 …stimulate the anterior pituitary gland to secrete hormones that… Thyroid gland Adrenal cortex Pituitary gland Gonad (Testis) 3 …stimulate other endocrine glands to secrete hormones Feedback Mechanisms slides 21-27 Feedback Mechanisms A mechanism by which the product(s) of a process can act as regulators of that process. Many biochemical processes are controlled by negative feedback mechanisms. Negative Feedback (more common) Positive Feedback (less common) Understanding Feedback Loops Allows understanding of anatomical location of pathology leading to abnormal function! Types of Pathology: 1) Hormone deficiency 2) Hormone excess 3) Hormone resistance Example of Hormone Negative Feedback Loop ADH aka vasopressin Example Feedback Loop (HPA Axis: HypothalamusPituitary-Adrenal cortex) “releasing hormone” CRH: Corticotrophinreleasing hormone “tropic hormone” ACTH: Adrenocorticotropic hormone Cortisol has many functions in the human body, such as mediating the stress response, regulating metabolism, the inflammatory response, and immune function Image from Vander, Sherman, and Luciano’s Human Physiology, 9th ed. Practice Question #1 1. What happens if hormone 1 is released in EXCESS? And its secretion cannot be inhibited via negative feedback Plasma hormone 1 level:___ Ant pit hormone 2 secretion:___ Endocrine gland hormone 3 secretion:___ Plasma hormone 3 level: ___ Target cell response to hormone 3: ___ 2. What might cause this? ______________________ Indicate as: High (after stimulus) or Higher (after stimulus and excess) or Basal (level before stimulus) Image from Vander, Sherman, and Luciano’s Human Physiology, 9th ed. Practice Question #2 1. What happens if hormone 2 is released in EXCESS? And its secretion cannot be inhibited via negative feedback Plasma hormone 2 level:___ Endocrine gland hormone 3 secretion:___ Target cell response to hormone 3:___ Hypothalamus hormone 1 secretion:___ 2. What might cause this? ______________________ Indicate as: High (after stimulus) or Higher (after stimulus and excess) or Basal (level before stimulus) Image from Vander, Sherman, and Luciano’s Human Physiology, 9 th ed. Practice Question #3 1. What if the anterior pituitary was damaged and unable to response to hormone 1? Plasma hormone 2 level:___ Endocrine gland hormone 3 secretion:___ Target cell response to hormone 3:___ Hypothalamus hormone 1 secretion:___ 2. What might cause this? ______________________ Indicate as: High (after stimulus) or Higher (after stimulus and excess) or Basal (level before stimulus) Image from Vander, Sherman, and Luciano’s Human Physiology, 9th ed. Hormone Actions slides 29-34 Hormones in the Blood Hormones circulate in the blood either free or bound – Steroids and thyroid hormone are attached to plasma proteins – All others circulate without carriers The concentration of a circulating hormone reflects: – Rate of release – Speed of inactivation and removal from the body Hormones are removed from the blood by Degrading enzymes Kidneys Liver Half-life—the time required for a hormone’s blood level to decrease by half Interaction of Hormones at Target Cells Multiple hormones may interact in several ways Permissiveness: one hormone cannot exert its effects without another hormone being present Synergism: the action of two hormones results in activity greater than the sum of the activity of each hormone alone. Antagonism: one or more hormones opposes the action of another hormone Target Cell Activation Target cell activation depends on three factors 1. Blood levels of the hormone 2. Relative number of receptors on or in the target cell 3. Affinity of binding between receptor and hormone Hormones influence the number of their receptors Up-regulation—target cells form more receptors in response to the hormone Down-regulation— target cells lose receptors in response to the hormone Target Cell Specificity Target cells must have specific receptors to which the hormone binds: ACTH receptors are only found on certain cells of the adrenal cortex On the other hand, thyroxin receptors are found in nearly all cells of the body Adrenocorticotropic hormone (ACTH) is a hormone produced in the anterior, or front part of the pituitary gland in the brain. The function of ACTH is to regulate levels of the steroid hormone cortisol, which released from the adrenal gland. Desensitization Refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly. Two types of desensitization, homologous and heterologous, were described. In homologous desensitization, only agonist-activated receptors are desensitized while in heterologous desensitization, both agonist-activated and non-activated receptors sharing the same signaling pathways are inactivated. Mechanisms of desensitization: 1) Down regulation of receptors 2) Receptor modification 3) Receptor endocytosis 4) Inhibition of signal transduction Mechanisms of Hormone Action Hormone action on target cells may be to: – Alter plasma membrane permeability of membrane potential by opening or closing ion channels – Stimulate synthesis of proteins or regulatory molecules – Activate or deactivate enzyme systems – Induce secretory activity – Stimulate mitosis – Alter metabolism