Download presentation
Presentation is loading. Please wait.
Published byMuriel Porter Modified over 9 years ago
1
Mechanisms of hormone actions Endocrine 412
2
Objectives hormones classifications. Defining hormones and their classifications. general characteristics of hormones. Listing the general characteristics of hormones. factors determining the response of target cells to hormones. Identifying factors determining the response of target cells to hormones. different mechanisms of action of hormones. Describing the different mechanisms of action of hormones. bind to cell surface receptors. Listing hormones that bind to cell surface receptors. bind to intracellular receptors. Listing hormones that bind to intracellular receptors.
3
General characteristics of hormones Hormones Hormones : special cells not are molecules that are produced by special cells (not by all cells of the body) directly to blood are secreted directly to blood (with no ducts) in very low concentrations in blood are available in very low concentrations in blood work in distant sites are transported in blood to work in distant sites systemic actions have systemic actions specificreceptors have specific receptors (either intra- or extra-cellular ) in target tissues specialmechanisms of actions have different special mechanisms of actions
4
Receptors of hormones Hormones are present in very low concentrations in extracellular fluids (e.g. blood) In order to initiate their biologic effects, target cells must recognize hormones by binding to specific receptors target cell is defined by its ability to bind selectively a given hormone via a receptor A target cell is defined by its ability to bind selectively a given hormone via a receptor Receptors have at least 2 DOMAINS Receptors have at least 2 DOMAINS: Recognition domain 1- Recognition domain: binds to the hormone Couplingdomain 2- Coupling domain: couples hormone recognition to some intracellular function by generating a signal Generally, COUPLING occurs by two ways: 1- Polypeptide hormones, protein hormones & catecholamines binding of hormones to extracellular receptors plasma membrane receptors (extracellular receptors). intracellularreceptors 2- Steroid & thyroid hormones interact with intracellular receptors, form complexes that generates a signal.
5
1-Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits The concentration of hormone as seen by target cells is determined by three factors:
6
2-Rate of delivery: An example of this effect is blood flow to a target organ or group of target cells – high blood flow delivers more hormone than low blood flow. 3-Rate of degradation and elimination: Hormones, like all biomolecules, have characteristic rates of decay, and are metabolized and excreted from the body through several routes. Hormones are cleared by Hormones are cleared by: 1- Metabolic destruction by tissues 2- Binding with tissues 3- Excretion by the liver into bile 4- Excretion by the kidney into urine 5- Clearance of protein bound hormones is slower than clearance of peptide hormones The concentration of hormone as seen by target cells is determined by three factors: The concentration of hormone as seen by target cells is determined by three factors: (cont.)
7
Classifications of hormones according Hormones are classified according to: 1- Chemical composition (protein or others) 2- Solubility (hydrophilic or lipophilic) 3- Location of receptors (intra- or extra-cellular) 4- Nature of signal used to mediate hormone action within cells According to their classifications, hormones are classified into Group IGroup II according to mechanism of action Group I & Group II (according to mechanism of action)
8
Classification of hormones according to mechanism of action: Group I intracellular receptors (cytosolic or nucleus) Hormones that bind to intracellular receptors (cytosolic or nucleus): Solubility 1- Solubility: lipophilic (to pass cell membrane which is mainly lipid) Chemical composition 2- Chemical composition: Derived from cholesterol (except: thyroid hormones & retinoic acid) Transport in blood 3- Transport in blood: Associate with transport proteins (to tackle solubility problem) Long plasma half-life 4-Mechanism of action 4-Mechanism of action: traversesreceptor 1- Free hormone traverses plasma membrane of cells & binds to receptor in cytosol or nucleus of target cells. HRE 2- Hormone-receptor complex binds to specific region in DNA of gene (hormone-response element, HRE) transcription 3- Binding causes activation or inactivation of specific gene(s) transcription (production of mRNA) protein synthesis 4- Accordingly, amount of protein synthesis (production) is changed (protein may be enzymes of metabolic react.) 5- Accordingly, certain metabolic processes are affected.
9
Example of Group I hormones: Steroid hormones via cytoplasmic receptors
10
Example of Group I hormones: Retinoic acid (active product of vitamin A) via nuclear receptors
11
List of Group I hormones Thyroid hormones Thyroid hormones Steroid hormones: Steroid hormones: Glucocorticoids (e.g. cortisol hormone) Glucocorticoids (e.g. cortisol hormone) Mineralocorticoids (e.g. aldesterone) Mineralocorticoids (e.g. aldesterone) Androgens (e.g. testosterone hormone) Androgens (e.g. testosterone hormone) Estrogens Estrogens Progestins (e.g. progesterone hormone) Progestins (e.g. progesterone hormone) Retinoic acid (active metabolite of vitamin A) Retinoic acid (active metabolite of vitamin A) Calcitriol (1, 25 DHCC, active metabolite of vitamin D) Calcitriol (1, 25 DHCC, active metabolite of vitamin D)
12
plasma membrane (extra-cellular) receptors Hormones that bind to plasma membrane (extra-cellular) receptors: Solubility 1- Solubility: hydrophilic Chemical composition 2- Chemical composition: Polypeptides, proteins, glycoproteins & catecholamines Transport in blood 3- Transport in blood: No transport protein- short plasma half-life Mechanismof action 4-Mechanism of action: Hormone binds to plasma membrane receptor second messenger Hormone -receptor interaction leads to generation of second messenger intracellularly that communicates (couples) hormones binding with intracellular metabolic processes Second messengers: 1- cyclic AMP (cAMP) 2- cyclic GMP (cGMP) 3- Calcium or phosphaitdyl inosiltol (or both) 4- Kinase cascade Classification of hormones according to mechanism of action: Group II
13
Second Messenger: cAMP
14
1- Second messenger is cAMP: 2 adrenergic Catecholamines Adrenocorticotropic Hormone (ACTH) Angiotensin II Antidiuretic Hormone (ADH) Calcitonin Human Chorionic Gonadotropins (hCG) Corticotropin-releasing hormone (CRH) Follicle Stimulating Hormone (FSH) Leutinizing Hormone (LH) Glucagon Ipotropin (LPH) MSH (Melanocyte Stimulating Hormone) Parathyroid Hormone (PTH) Somatostatin Thyroid Stimulating Hormone (TSH) List of Group II hormones
15
1- Second messenger is cGMP Atrial natriuretic peptide (ANP) Nitric Oxide (NO) There are two isoforms of guanylate cyclase involved in production of cGMP: membrane-bound A membrane-bound guanylate cyclase ( for ANP & bacterial endotoxin) cytosolic A cytosolic guanylate cyclase (for NO) List of Group II hormones
16
Second messenger cGMP: Atrial Natriuretic Peptide
17
Nitric Oxide Synthase NO Binds to heme moiety of guanylate cyclase Conformational change of the enzyme Increased activity (production of cGMP) Modulation of activity of other proteins (protein kinases, phospho- diesterases, ion channels) Physiological response (relaxation of smooth muscles, inhibition of platelet aggregation, etc.) NO signaling in physiology O2-O2- ONOO-
18
Second Messenger: Phosphatidyl inositol & calcium
19
Second messenger is phosphatidyl inositol or calcium (or both together) Acetylcholine 1 adrenergic catecholamines Angiotensin II Antideuretic Hormone (ADH) Cholecystokinin Gastrin Gonadotropin –Releasing Hormone (GnRH) Oxytocin Platelet Derived Growth Factor (PDGF) Substance P Thyrotropin Releasing Hormone (TRH) List of Group II hormones
20
Binding of insulin on -subunits Of insulin receptors Phosphorylation of -subunits Of insulin receptors Phosphorylation of insulin response substrates (IRS) CHANGE IN Gene Metabolism Growth Expression Second Messenger: Kinase cascade (for insulin hormone)
21
Second messenger is kinase cascade: Chorionic somatomammotropin (CS) Epidermal Growth factor (EGF) Erythropoeitin (EPO) Antideuretic Hormone (ADH) Fibroblast Growth Factors (FGF) Growth Hormone (GH) Insulin Insulin-like Growth factors (IGF-I & IGF-II) Nerve Growth Factor (NGF) Platelet Derived Growth Factor (PDGF) Prolactin (PRL) List of Group II hormones
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.