Dr. M. Zaharna (2014) Endocrinology Introduction

Dr. M. Zaharna (2014) Communication of Cells The continued function of multicellular organism requires that the internal environment be maintained constant within narrow limits—no matter what conditions prevail in the external environment Effective communication between different parts of the body is absolutely essential for the functioning of any multicellular organism 2

Dr. M. Zaharna (2014) Communication of Cells This is achieved through different communication modes 3

Dr. M. Zaharna (2014) The Endocrine System An integrated network of multiple organs derived from different embryologic origins that release hormones ranging from small peptides to glycoproteins, which exert their effects either in neighboring or distant target cells This endocrine network of organs and mediators does not work in isolation, and is closely integrated with: – the central and peripheral nervous systems – as well as with the immune systems 4

Dr. M. Zaharna (2014) Function The function of the endocrine system is to coordinate and integrate cellular activity within the whole body by regulating cellular and organ function throughout life and maintaining homeostasis. Homeostasis, or the maintenance of a constant internal environment, is critical to ensuring appropriate cellular function. 5

Dr. M. Zaharna (2014) Components of the Endocrine system 1.Endocrine glands 2.Hormones 3.Target organ 6

Dr. M. Zaharna (2014) Components of the Endocrine system 1.Endocrine glands – The classic endocrine glands are ductless – Secret their chemical products (hormones) into the interstitial space from where they reach the circulation – Unlike the cardiovascular, renal, and digestive systems, the endocrine glands are not anatomically connected and are scattered throughout the body 7

Dr. M. Zaharna (2014) Endocrine glands are located throughout the body 8

Dr. M. Zaharna (2014) Components of the Endocrine system 2.Hormones – chemical products, – released in very small amounts – elicits a typical physiological response in other cells – can be released from the endocrine glands (ie, insulin, cortisol), the brain (ie, corticotropin-releasing hormone, oxytocin, and antidiuretic hormone), and other organs such as: – the heart (atrial natriuretic peptide), – liver (insulin-like growth factor-I), – and adipose tissue (leptin) 9

Dr. M. Zaharna (2014) Components of the Endocrine system 3.Target organ – The target organ contains cells that express hormone-specific receptors – and that respond to hormone binding by a demonstrable biologic response 10

Dr. M. Zaharna (2014) Hormones Hormones are a class of signaling molecules Hormones communicate this effect by: – their unique chemical structures recognized by specific receptors on their target cells, – and their concentrations in the general or localized circulation. 11

Dr. M. Zaharna (2014) Functions of hormones Their functions can be broadly grouped into several categories: Reproduction, sexual differentiation Growth and development Mobilization of body defenses Maintenance of the internal environment Regulation of metabolism 12

Dr. M. Zaharna (2014) Functions of hormones A single hormone may affect more than one of these functions – For example, thyroid hormone is essential in development as well as many aspects of homeostasis and metabolism and each function may be controlled by several hormones – For example, the control of blood glucose which involves insulin and its counter regulatory hormone, glucagon, as well as cortisol, growth hormone and epinephrine 13

Dr. M. Zaharna (2014) Hormone Effects 14

Dr. M. Zaharna (2014) Hormone Effects a)Endocrine when a hormone is released into the circulation and then travels in the blood to produce a biologic effect on distant target cells b)Paracrine when a hormone released from one cell produces a biologic effect on a neighboring cell, which is frequently a cell in the same organ or tissue c)Autocrine when a hormone produces a biologic effect on the same cell that released it d)Intracrine when a hormone is synthesized and acts intracellularly in the same cell 15

Dr. M. Zaharna (2014) Levels at which hormone actions are considered 16

Dr. M. Zaharna (2014) Hormone synthesis Hormone synthesis occurs in response to specific biochemical signals induced by a wide range of regulatory systems 17

Dr. M. Zaharna (2014) Stimulation of Hormone Synthesis Humoral: in response to changing levels of ions or nutrients in the blood Neural: stimulation by nerves Hormonal: stimulation received from other hormones 18

Dr. M. Zaharna (2014) Synthesis of Hormones The classical hormones fall into four categories: – Peptides/proteins, which comprise the largest and most diverse class of hormones (vasopressin, insulin) – Steroids, which are derivatives of cholesterol ( Estrogen and testosterone) – Derivatives of the amino acids tyrosine or tryptophan (adrenaline, noradrenaline) – Derivatives of phospholipids 19

Dr. M. Zaharna (2014) Synthesis of Protein Hormones 1.Transcription of the DNA sequence into RNA 2.Excision of sequences (introns) from the initial DNA transcript and modifications of the 3′ and 5′ terminals 3.Translation of the mRNA into a protein (the signal sequence is rapidly cleaved) 4.The prohormone is cleaved into fragments, a process that normally occurs prior to secretion 20

Dr. M. Zaharna (2014) Synthesis of Protein Hormones Since protein and peptide hormones are stored in, and secreted from, secretory granules it is necessary for their synthesis and packaging to take place within membrane-bound structures of the cell Postsynthetic processing begins in the endoplasmic reticulum as the hormone precursors are translocated to the Golgi apparatus for final processing and packaging for export 21

Dr. M. Zaharna (2014) Synthesis of Protein Hormones The signal peptide, of proteins destined for secretion enters the cisternae of the endoplasmic reticulum even as peptide elongation continues In the endoplasmic reticulum – the signal peptide is removed; – the protein is folded with the assistance of protein chaperones, – sulfhydryl bridges may form, – and carbohydrate may be added (glycosylation) – The partially processed protein is then entrapped in vesicles that bud off the endoplasmic reticulum – fuse with the Golgi apparatus, where glycosylation is completed, and – the protein is packaged for export in secretory vesicles in which the final stages of processing take place 22

Dr. M. Zaharna (2014) Steroids Hormones The synthesis of steroid hormones that occurs in the mitochondria and rough endoplasmic reticulum does not require immediate gene expression It requires the presence of specific enzymes that convert cholesterol into the appropriate steroid the same basic ring structure and despite superficial 2D structural similarity, the side chains and spatial orientation generate specificity 23

Dr. M. Zaharna (2014) Amino acids derived Hormones The amine hormones are formed by side- chain modifications of either a single tyrosine or tryptophan molecule 24

Dr. M. Zaharna (2014) Phospholipids Derived Hormones The eicosanoid family of hormones are formed from lipids Finally, hormones derived from lipids and phospholipids include the major classes of eicosanoids including prostaglandins, prostacyclins, thromboxanes and leukotrienes 25