Endocrine System AMIR SAMADIAN M.D. DEPARTMENT OF PHYSIOLOGY Forms of cell to cell communication! https://lh5.googleusercontent.com/VKgatcTlzji5uzb0zhog_Vw0FzIihsaQuRt6znuqSrPEJkh7uqHoE8dYIATqPsZmP vTqu-LwhyKSEctzUWqbJ4Py1IET5Lkc0DWMdtVKzWyKp-1AZOR0JkHukoB8BCp8pYa--tM Endocrine system ▪ Works with Nervous system to maintain homeostasis ▪ Glands 🡪 produce specific signaling molecules (Hormones) ▪ Hormones will be released into the blood ▪ Bind to their specific receptor on target tissue 🡪 Physiological response ! https://lh4.googleusercontent.com/VZ3yIQ5snQuK7ihh3S4bSDIIgmolU9SMtggskB-ulxMp-5VEgIjbSioav7uyMSUn8 jb5131HR9FydU_Ywcz5hGepqK6OnU8_XSruJqJ9TOB_97ellWLObPKBrsVA1Ml_IdJ0Pyg https://lh6.googleusercontent.com/RQ1ge9Tknzf_lIFryclMMxN5wbXW2SmfoX5kwjLJ8SWTllDXCiVb4GF-wqsaDJQ0X _RXVPlKNNFlu7KEmLwnhBQv_tJQoslswdRKf-U9T2noK5Mhy8mU9w9I2rbdf2RGKScV_lo Hormones overview Endocrine System Hormones can be Hydrophilic or lipophilic •Water soluble hormones (Peptides and protein) can not pass membrane 🡪 bind to peripheral receptors on the surface of the cell , eg : G-protein-coupled receptors or Tyrosin kinases •Lipid soluble hormones ( Steroids, Thyroid-hormones ) can pass cell membrane 🡪 act on cytoplasmic or nuclear receptor to alter gene expression https://lh3.googleusercontent.com/PWYJySACkAoyE7_Xg7ebiknYHFRyfeGzp2Tl7qLzBSp_hi7uW-lAkOoopSSjjK3cw IegGBKVQWifIhYFXDJw0_IveDvZ-uwzrtTK5sq18vLwk0OMQHx3wKUK9bJV9sUJNHAJenk Protein bound and free circulating hormone Factors determining the magnitude of response in target cell ▪ Concentration of circulation hormone ▪( Dose – response relation ) : higher the dose 🡪 higher the response ▪ Number of receptors and their affinity for the hormone Regulation of hormone secretion Negative vs positive feedback Regulation of reception Cell response : receptors up/down regulation mage result for down and up regulation of receptors Gs/i 🡪 cAMP 🡪 Protein kinase A Engineering therapeutic antibodies targeting G-protein–coupled receptors | Experimental & Molecular Medicine Gq 🡪 PL C 🡪 DAG & IP3🡪 PK C Steroid hormone cell response mechanism Mechanism of signal transduction (summary) Hypothalamo-Hypophysial Axis Pituitary gland, adenohypophysis (anterior lobe) - Neuroanatomy Flashcards | Draw it to Know it Hypothalamo pitutary hormons Pitutary in a nutshell Vascular endothelial cell function Major functions of endothelial cells: regulation of vascular tone, control of VSMC proliferation, inflammation, permeability, angiogenesis, metabolism and hemostasis. Ang II, angiotensin II; CAMs, cell adhesion molecules; CCL; chemokine (C-C motif) ligand; EC, endothelial cell; EDHF, endothelium derived hyperbolizing factor; EGF, epidermal growth factor; ET1, endothelin-1; FGF, fibroblast growth factor; H 2 S; hydrogen sulfide; HSPG, heparan sulfate proteoglycans; ICAM, intercellular adhesion molecule; NO, nitric oxide; PAF, platelet-activating factor; PAI-1, Plasminogen activator inhibitor-1; PDGF, platelet-derived growth factor; PGH 2 , prostaglandin H 2 ; PGI 2 , prostacyclin; ROS, reactive oxygen species; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TGF-β, transforming growth factor-β; t-PA, tissue plasminogen activator; TXA 2 ; thromboxane A 2 ; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor; VSMC, vascular smooth muscle cells; vWF, von Willebrand factor. RAAS and AG II •Is activated to preserve Volume and maintain the Blood pressure This is done by : 1.Vasoconstictrion 🡪 increase TPR 2.Increasing Na+ resorbtion 🡪 increase Preload 🡪 increase in CO 3.Both of which increase MAP Natriuretic peptides (opposing RAAS) Natriuretic peptides Cardiovascular and Renal Actions of Natriuretic Peptides ▪Natriuresis ▪Diuresis ▪Improve glomerular filtration rate & filtration fraction ▪Inhibit renin release ↓ circulating angiotensin II ↓ circulating aldosterone ▪Systemic vasodilation ▪Arterial hypotension ▪Reduced venous pressure ▪Reduced pulmonary capillary wedge pressure https://upload.wikimedia.org/wikipedia/commons/f/f7/Energy_Balance.png https://qph.fs.quoracdn.net/main-qimg-c8f81e0a9ecef2935183f4dc1e0b48d3 Increase in white adipose tissue and changes in related hormones Adipose tissue as an endocrine organ: many functions and products. IL-6, interleukin-6; NEFA, non-esterified fatty acid; PAI-1, plasminogen-activator-inhibitor-1; TNF-α and-β, tumor necrosis factor-α and-β Pathophysiology of Obesity (Increase in WAT mass ) ▪ Increase in AGE → increase in BP (HTN) ▪ Increase in PAI-1 → inhibiting fibrinolytic system 🡪 Clotting 🡪 Risk of CVD ▪ TNF-a & IL-1 → disruption of insulin signaling 🡪 insulin resistance ▪ Excess leptin → leptin resistance 🡪 obesity and insulin resistance 🡪 type 2 DM ▪ Decrease in adiponectin → decrease Gluc uptake & Pro-inflammatory condition in endothelial cells → risk of type 2 diabetes & CVD respectively. ▪ excess resistin → decrease insulin mediated Glu uptake 🡪 type 2 DM Leptin as a marker of long-term energy storage and acute changes in energy intake (keeps you thin) IVD Antibody Development Services for Leptin Marker - Creative Biolabs Factors promoting leptin secretion Excess energy stored as fat (obesity) Overfeeding Glucose Insulin Glucocorticoids Estrogens Inflammatory cytokines, including Tumor Necrosis Factor-α and Interleukin-6 (acute effect) Factors inhibiting leptin secretion Low energy states with decreased fat stores (leanness) Fasting Catecholamines and adrenergic agonists Thyroid hormones Androgens Peroxisome Proliferator-activated Receptor-γ (PPARγ) agonistsc Inflammatory cytokines, including Tumor Necrosis Factor-α (prolonged effect) Proposed salutary effects of adiponectin. Adiponectin Plasma adiponectin concentration has inverse correlation with body fat mass ie, the less WAT you have 🡪 higher is your adiponectin plasma level High levels of Adiponectin is beneficial and protective against Type 2 DM and CVD Summary overview of physiological and cellular changes in response to either recombinant adiponectin protein or endogenously overproduced adiponectin. POMC: The Physiological Power of Hormone Processing | Physiological Reviews