Endocrine Physiology PDF

Endocrine Physiology 1  Homeostasis & Controls Successful compensation – Homeostasis reestablished Failure to compensate Pathophysiology Illness Death 2...

Endocrine Physiology 1  Homeostasis & Controls Successful compensation – Homeostasis reestablished Failure to compensate Pathophysiology Illness Death 2 Death  Regulation of homeostasis 1. The nervous system: Regulates homeostasis through generation of action potentials and by releasing chemical messengers called neurotransmitters 2. The endocrine system: Regulates homeostasis by releasing chemical messengers called hormones (First messengers) Difference between hormones and neurotransmitters Speed of action Duration of action Distribution Common aspects: – Released in small quantities – regulate other cells & tissues (effectors) – act through receptors – Need mediators – functional overlap between some hormones & NTs 3 – Both work towards common goal  The endocrine system Nervous system broadcasts its hormonal messages to essentially all cells by secretion into blood and extra cellular H fluid. Like a radio broadcast, it requires a Nerve Impulse receiver to get the message –For this purpose cells must bear a receptor for the hormone being broadcast in R order to respond. NTs R Effector cell Effector cell 4 A cell is said to be a target cell if it has a specific receptor for the hormone Hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bears receptors for the hormone. 5 INTERCELLULAR SIGNALLING Cells need to be able to communicate with other cells and respond to environmental changes  For multi-cellular organisms, cell-cell communication is important  For unicellular organisms, they need to be able to respond to physical and chemical changes in their environment 6 Effects of Cellular Signalling 7 Four forms of intercellular signalling (for cell-cell communication) 8 Same signal can cause different reactions depending on the target cell 9  10 Cell-surface receptor versus intracellular receptor Functions of hormones 1. Regulation of reproduction: gametogenesis, sexual desire, coitus, fertilization. 2. Regulation of body growth and development. 3. Production, utilization and storage of energy 4. Homeostasis: maintenance of the internal environment in the body (maintaining the optimum biochemical environment). -Water-electrolyte balance (stability of body fluid composition) -Regulation of ABP -Control of BT, emotion -Change in mass of bone, muscle and fat 11 Chemical nature of hormones 1. Amines (derived from tyrosine) Hydroxylation - catecholamines Iodination - thyroid hormones 2. Peptides/polypeptides or proteins 3. Steroids (derived from cholesterol) Adrenocorticoids Sex hormones Active metabolites of vitamin D3 4. Eicosanoids (derived from fatty acids) - Prostaglandins - Leukotrienes and - Thromboxanes 12 Amine Hormones: Structure 13 Steroidal Hormones: Structure Figure 7-6: Steroid hormones are derived from cholesterol 14 Steroid Hormones  All steroidal hormones are derived from cholesterol and differ only in the ring structure and side chains attached to it.  All steroid hormones are lipid soluble 15 Fatty Acid Derivatives - Eicosanoids Fatty Acid Derivatives - Eicosanoids Eicosanoids are a large group of molecules derived from polyunsaturated fatty acids. The principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes and thromboxanes. 16  Classes of Hormones (Solubility) The hormones fall into two general classes based on their solubility in water. The water soluble (Hydrophilic hormones) hormones are the catecholamines (epinephrine and norepinephrine) and peptide/protein hormones. The lipid soluble (Lipophilic hormones) hormones include thyroid hormone, steroid hormones and Vitamin D3 17 Types of Receptors 1. Receptors for the water soluble hormones are found on the surface of the target cell, on the plasma membrane (surface receptors). These types of receptors are coupled to various second messenger systems which mediate the action of the hormone in the target cell. 2. Receptors for the lipid soluble hormones reside in the nucleus (and sometimes in the cytoplasm) of the target cell (intracellular receptors). Because these hormones can diffuse through the lipid bilayer of the plasma membrane, their receptors are located on the interior of the target cell 18 Hormone: Synthesis, Storage, Release and Transport Site of synthesis: Protein/peptide hormones: in the rER Steroid hormones: in the sER Storage: Protein/peptide hormones: preprohormones in vesicles Steroid hormones: Cholesterol Release: Exocytosis Transport: hormones are transported in blood in two forms: 1. In the free form 2. In combination with plasma proteins (albumin & globulin). It has 2 advantages a. Prolong the biological half life of hormones b. Serve as a reservoir of hormones Metabolism: metabolized in the liver or by target cells Excretion: urine, feces, sweat 19 Protein and Polypeptide Hormones: Synthesis and Release 20 Mechanism of Action of Hormone Hormones perform their action via three mechanisms. Direct membrane effect Via activation of the second messengers Direct activation of the gene 21  Hormone Receptors Location Cytosolic or Nuclear – Lipophilic ligand enters cell – Often activates gene – Slower response Cell membrane – Lipophobic ligand can't enter cell – Outer surface receptor Hydrophilic – Fast response 22 Direct Membrane Effect of Hormones Hormone H Receptor Cell membrane Hormone-receptor interaction alters membrane permeability by either Opening or closing of pores (channels) Conformational change of carriers, Activation/inactivation of pump mechanisms 23 Second Messengers Involved in Cell Signalling  cAMP  cGMP  Phospholipase-C/IP3  Ca/calmodulin  tyro kinases  DAG One hormone can use several systems (in various cells or for different functions) 24  Protein and Polypeptide Hormone Receptors Binds to surface receptor Transduction System activation – Open ion channel – Enzyme activation Second messenger systems Protein synthesis 25 Steroid Hormones: Action 26  Regulation of Hormonal Secretion Hormonal secretion is regulated by at least 3 Mechanisms. 1. Feedback regulatory mechanisms Negative feedback mechanism (most hormones) Positive feedback mechanism (LH- surge) 2. Nervous control of hormonal secretion Secretion of OT, ADH, AD, NA 3. Circadian rhythm (periodic variations) Cortisol, sex hormones 27 Feedback Control of Hormone Production Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion 28 Regulation of Hormone Release Negative feedback mechanism  hormone Target tissue Gland Endocrine gland inhibition product 29 Regulation of Hormone Release Positive feedback  hormone Target tissue Gland Endocrine gland enhances product 30 LH Surge: the positive feedback mechanism GnRH HT Pituitary inactivates LH Ovary Estrogen >200 µg/ml 31 Feedback control of insulin by glucose concentrations 32 BGL Negative feedback effects of cortisol 33 Episodic Secretion of Hormones The most prominent episodes of release occur with a frequency of about one hour—referred to as circhoral An episode of release longer than an hour, but less than 24 hours, the rhythm is referred to as ultradian If the periodicity is approximately 24 hours, the rhythm is referred to as circadian – usually referred to as diurnal because the increase in secretory activity happens at a defined period of the day. 34 Circadian (chronotropic) Control 35 Major Endocrine Glands 36 Other Organs Having Endocrine Function The pineal gland: Hormone: Melatonin Function: Inhibits gonadal function and delays the onset of puberty. The thymus gland: Hormone: Thymopoietin Function: Stimulates lymphocyte proliferation Endocrine function of the heart: Hormone: ANP (atrial natriuretic peptide) Function: Nartiuresis Renin secretion GFR Aldosterone secretion Vasodilator 37  Other organs having endocrine function (cont´d) Endocrine function of the kidneys Hormones: Renin, erythropietin Calcitriol (1, 25 (OH)2 D3) Function: RAS Ang-II Ang-II - A potent vasoconstrictor - Aldosterone secretion - ADH secretion - Stimulates the thrist center - Salt and water reabsorption Ang-II receptors: AT1A-R: on BVs, renal tubules AT1B-R: on adrenal cortex AT2-R: on neurons Endocrine function of the liver Hormones: Erythropietin Somatomedin-C (1, 25 (OH)2 D3) GIT hormones: Gastrin, Secretin, CCK, VIP, Sub-P ect. 38 Ectopic hormones: Summary of the Endocrine System 39