CSB325 Lecture 3 Review Notes

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University of Toronto St. George
Cell and Systems Biology
David Lovejoy

CSB325 Lecture 3 – Introduction to Endocrinology Philosophical aspects - Claude Bernard in the 1800s  endocrinology was defined as secretions from ductless glands  secretions were to maintain a physiological balance or homeostasis within an organism  led to isolation of hormones such as insulin and secretin in the early 1900s - In the early 20 century  description of the neurosecretory cell and neuroendocrine circuits  led to isolation of active molecules in all tissues  endocrinology redefined as the study of signaling molecules  signaling molecules were produced by one cell type to signal another cell type (e.g., concept of cell-to-cell and tissue-to-tissue communication) - In the last 30 years  advent of information theory was applied to endocrinology  endocrinology and signaling molecules became associated with the transfer of information from one tissue or cell to another tissue or cell - Endocrinology involves homeostasis, cell signaling, communication, and information transfer Definition of hormones - Hormone is one type of signaling molecule that is released by a tissue into the blood stream and interacts with another tissue - However, hormone is frequently considered to be synonymous with signaling molecules Types of signaling mechanisms - Autocrine o A chemical released from a cell binds to a receptor on the same cell or an identical cell to modulate the activity of that cell  Do not utilize a vascular system  Cells must be in close proximity - Paracrine o A chemical released from a cell binds to a receptor on a different type of cell - Juxtacrine o Between two cells or the cell and the extracellular matrix  Direct interaction  Membrane-bound ligand binds to membrane-bound receptor o E.g., delta (ligand) binds to notch (receptor)  Components of the ECM binds to membrane-bound receptor  Stationary - Intracrine o Molecules that transfer information or signal between organelles in a cell - Endocrine o Endocrine component releases hormone into the blood stream and interacts with another tissue o Endocrine gland  secretory cells secretes hormone directly into the bloodstream (endocrine signaling) or by diffusion into surrounding tissue (paracrine signaling) o Endocrine systems  Any cell with paracrine signaling  potential to become an endocrine cell  These cells were present in all the basic tissue types of the earliest metazoans  All tissues  potential to become endocrine organs  All tissues and organs  secrete a variety of substances into the blood stream  Therefore, all organs = endocrine organs - Neuroendocrine o Sensory information  nervous component  neuroendocrine component (e.g., hypothalamus)  endocrine component (e.g., pituitary)  tissues - Exocrine o Release of signaling molecules (called pheromones) from one organism to another  Act as chemical espionage, sex attractants, or reproductive regulators  Part of a larger group of exocrine signals called semiochemicals Types of signaling systems - Growth and differentiation  mostly receptor kinase systems o Feeding o Growth o Maturation o Cell cycle o Differentiation o Cell death - Sensory systems  mostly G-protein coupled receptors o Locomotion (toward food source; away from danger) o Chemical (olfactory input) o Visual (input) o Geotaxis o Mechanical Types of signaling molecules - Amino acids o Among first amino acids synthesized o Acid/based ability o Form elongated chains o Modified amino acids  Amino acids can be modified into additional signaling molecules  The genes encode the enzymes that regulate the biosynthetic pathway  The expression of the genes is cell and tissue dependent  The enzymes will differ depending on the cell and tissue type  Glycine, glutamate, GABA  →  Catecholamine  → → → → →  Monoamine  → → → →  Thyroid hormone  o One iodine on the first ring and two iodines on the second ring o Two iodines on the first ring and one iodine on the second ring  reverse T3  → o Two iodines on both rings o Acetylcholine  Not technically a modified amino acid  → - Peptides and proteins o Structural and signaling ability o Several types of structural organization o Can carry and transmit information o Peptide bond formation between two amino acids via condensation reaction o Possess information at all levels of organization (e.g., primary, secondary, tertiary, quaternary) - Lipids o Pass through lipid membrane o Early prebiotic synthesis o Fatty acid based hormones  Eicosanoids  Synthesized from arachidonic acid o Steroid hormones  Synthesized from cholesterol in the ER or mitochondria  Progestins (C21)  Corticosteroids (C21)  Aldosterone (C21)  Androgens (C19)  Estrogens (C18)  Vitamin D3 (C27)  Cholesterol (C27) - Gases and ions o Present in prebiotic Earth - Nucleic acids o Common as (intracrine, but also exocrine) signaling molecules o Evolutionary origins are not clear o Cyclic nucleotides
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