BIOM*3200: The Endocrine System

• The Endocrine System is the focus of BIOM*3200, this lecture takes place on February 11, 2025, taught by Vanessa Zak
• Instructing style combines text, pictures, videos, examples, and question/answer segments, supporting visual, auditory, read/write, and kinesthetic learning styles

Academia Journey

• BSc Honours in Biomedical Science
• 3rd-year research assistantship in Pathobiology
• Direct transfer to PhD during MSc year 2
• Focus on mitoepigenetics and mammalian male fertility

Readings

• Version 12: Focus on specific sections of Chapter 1 and Chapter 11
• Version 13 & 14: Includes same sections as Version 12, but with slightly different page numbers
• Version 15 & 16: Focus on slightly different sections and page ranges in Chapter 1 and Chapter 11

Learning Outcomes

• Understand homeostasis and the endocrine system
• Define hormones
• Explain levels of hormone effect (autocrine, paracrine, endocrine)
• Describe modes of secretion
• Understand receptor binding

Introduction to Homeostasis

• Homeostasis is a conceptual framework for physiology
• Claude Bernard (1813-1878) is the "Father of modern physiology"
• Internal environment remains constant despite external changes
• Provides stable conditions for cells in the body
• Walter Cannon (1871-1945) coined "homeostasis"

Homeostasis Explained

• Homeostasis describes the relative stability of the internal environment
• The body detects shifts using sensors, which communicate with an integration/control center
• The effector then initiates a response to return the body to a normal range

Homeostatic Control

• Relies on sensors that monitor conditions, an integrating center that coordinates responses, and response systems that enact changes
• Negative feedback loops are typically utilized

Home Furnace System

• Thermostats act as sensors
• When the house temperature decreases, heat is produced
• When the house temperature increases the furnace switches off

Blood Pressure Homeostasis

• Blood is evenly distributed throughout the body when lying down
• When standing, blood pools in the legs
• Reduced venous return decreases cardiac output, so blood pressure falls
• Baroreceptors respond by modulating sympathetic and parasympathetic outflow to increase vascular resistance, venous return, and cardiac output
• This limits the drop in blood pressure
• Inadequate or delayed responses can result in postural hypotension

Regulatory Systems

• Nervous and endocrine systems regulate water, electrolytes/pH, nitrogenous compounds, oxygen, carbon dioxide, temperature, and toxicants
• Regulation maintains homeostasis and metabolic processes

Endocrine System & Homeostasis

• Disease can be defined by a loss of homeostasis
• Dysregulation of mediators can lead to endocrine system dysregulation
• Many are affected by endocrine disorders

Importance of Understanding the Endocrine System

• Understanding helps in treating diseases
• Diabetes mellitus is a leading cause of death in Canada
• Thyroid disorders and endocrine ovarian disorders (common cause of infertility) affect many
• Diabetes is globally widespread and predicted to affect increasing numbers

Endocrine Disfunctions

• Hyper-function: too much hormone
• Hypo-function: too little hormone
• Resistance: too little effect

Endocrine System

• The study of hormones and their actions, regulates animal physiology and behavior
• Hormone originates from the Greek term "to excite or arouse"

Endocrine Gland

• Tissue releases a substance (hormone) into the bloodstream, influencing a target cell
• Includes, the pineal gland, hypothalamus, pituitary gland, thyroid gland, parathyroid glands, thymus, adrenal glands, pancreas, ovaries, and testes

Defining Hormones

• Classic Minkowski experiment (1889) indicates surgically removing the pancreas in a dog leads to diabetes; implanting pancreas pieces prevents the symptoms
• Banting & Best (1921) identified insulin to prevent elevated blood glucose levels

Insulin Function

• Insulin is a peptide hormone
• Produced by beta cells of the pancreas
• Promotes glucose absorption from blood to muscle/fat tissue
• Stored as an inactive hexamer with zinc ions and histidine residues
• Active form is a monomer

Hormone Types

• Most hormones are proteins and polypeptides (<100 amino acids)
• Steroids are cholesterol derivatives
• Glycoproteins and Amines (catecholamines or thyroid)

Hormone Action Levels

• Autocrine: Affecting the same cell
• Paracrine: Affecting adjacent cells
• Endocrine: Hormones secreted into the bloodstream affect distant target cells

Hormone Secretion Modes

• Peptide hormones like insulin are synthesized in advance, stored in secretory vesicles, and released via exocytosis
• Steroids diffuse on demand
• Amines are synthesized in advance, stored in secretory vesicles, and released via exocytosis or diffusion
• Transport in blood varies: dissolved in plasma or bound to carrier proteins
• Half-life varies

Receptor Binding Specificity

• Hormones bind to receptors on target cells with high specificity
• There is continuous turnover of the receptor-hormone complex
• Most hormone receptors are on the plasma membrane, except for steroid and thyroid hormones

Transmembrane Receptors

• Hormones bind to extracellular domain & activate cytoplasmic signaling pathway
• Pathways involve phosphorylation and enzyme activation
• Pathways lead to DNA/mRNA/protein responses or have local effect

Adenylate Cyclase Pathway

• Hormone binds to receptor, G-proteins dissociate
• G-alpha subunit activates adenylyl cyclase (AC)
• AC catalyzes cAMP production
• cAMP removes regulatory unit from PKA, which activates other molecules

Epinephrine & Adenylate Cyclase

• Epinephrine binds to β-adrenergic receptors, activating G-proteins
• G-protein subunits activate adenylyl cyclase
• Adenylyl cyclase catalyzes ATP conversion to cAMP
• cAMP activates PKA
• PKA phosphorylase converts glycogen to glucose-6-phosphate, turning into glucose released from the liver

Lefkowitz & Kobilka

• Received the 2012 Nobel Prize in Chemistry for work on G protein-coupled receptors

Phospholipase C-Ca2+ Pathways

• Hormone binds to receptor, causing G-proteins to dissociate and activate PLC
• PLC causes breakdown of membrane phospholipid to IP3
• IP3 binds to the endoplasmic reticulum, releasing stored Ca2+ into the cytoplasm
• Ca2+ activates other molecules

Alpha vs Beta-Adrenergic Receptors

• Alpha-adrenergic receptors activate phospholipase C (via Gq)
• Beta-adrenergic receptors activate adenylate cyclase (via Gs)
• G-alpha subunits are divided into subtypes

Steroid Hormone Receptors

• Steroid hormones are transported via plasma carrier proteins
• Then diffuse across the membrane
• Steroid hormone binds to a cytoplasmic receptor and translocates to the nucleus where it binds to DNA and acts as a transcription factor

Thyroid Receptors

• Thyroxine (T4) binds to carrier protein
• T4 converts to T3, which uses binding proteins to enter the nucleus
• The hormone-receptor complex binds DNA, leading to mRNA and protein production