PHCL 2600 - Week 11 Notes
PHCL 2600 - Week 11 Notes PHCL2600
Popular in Funct Anat and Pathophysiol I
Popular in Pharmaceutical Sciences
This 11 page Class Notes was uploaded by Emily Notetaker on Saturday November 7, 2015. The Class Notes belongs to PHCL2600 at University of Toledo taught by Williams,F in Fall 2015. Since its upload, it has received 22 views. For similar materials see Funct Anat and Pathophysiol I in Pharmaceutical Sciences at University of Toledo.
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Date Created: 11/07/15
Lecture 2 0 Carrier Proteins for Lipid Soluble Hormones 0 General carrier proteins I Albumin 0 Steroids 0 Some thyroid hormones I Transthyretin o Thyroid hormones 0 Some steroids 0 Specific carrier proteins I Cortisol binding globulin CBG 0 Cortisol and aldosterone I Thyroxine binding globulin TBG o Thyroid hormones I Sex steroid binding globulin TEBG 0 Testosterone and estradiol 0 They require carrier proteins to make them soluble 0 Control of Hormone Secretion o I Signals from nervous system I Chemical changes of molecules in the blood I Other hormones o I Negative feedback 9 most common I Positive feedback 0 Control of Hormone Secretion o 0 Most endocrine glands under 0 Cells can sense the magnitude of the biological effect produced by the hormone and decrease response 0 Based on magnitude of the effect produced by the hormone cell can decrease response 0 hypothalamuspituitaryorgan axis 0 Control of Hormone Secretion o I Less common 0 I Increases production and release of oxytocin to o Enhance milk production and release 0 Enhance contractions during childbirth Hormone Activity 0 Hormones affect only specific target tissues 0 Only target tissues or cells With a receptor for a specific hormone respond to the hormone Response depends on both hormone and target cell 0 Target cells respond differently to the same hormone I Hormonal effects vary Hormone Activity Receptor 0 o Hormone locks onto a specific receptor 0 Binding of hormone to the receptor unlock the cell s response producing an effect Regulation of Hormone Effects 0 Downstream effect determined by I Number of receptors present I Amount of hormone secreted o Receptors are constantly synthesized and broken down I Downregulation I Upregulation I Increase in hormone leads to decrease in number of receptors I Target cell is less sensitive to hormone O I Increase in hormone leads to increase in number of receptors I Target cell is sensitive to low concentrations of hormone o Hormone binds to a receptor on a target cell 0 Watersoluble hormones bind to receptors on the plasma membrane 0 Lipidsoluble hormones bind to receptors inside target cells I Cytoplasmic or nuclear 0 Surface Receptors for I Single transmembrane protein I Membrane bound protein I 7transmembrane protein G proteincoupled receptor 0 Hormone binds to receptor 0 Leads to I Molecular Response I Cellular Response I Tissue Response o Membranebound receptors I Receptors alter the activity of G proteins 0 Open or close ion channels and activate existing enzymes 0 Cell Response I Receptors alter the activity of intracellular enzymes 0 Activate existing enzymes 0 Cell Response 0 Intracellular receptors I Activate genes 0 Synthesize new proteins or enzymes 0 Cell Response 0 produce responses through the action of I o protein is activated by G proteins 0 Effector produces a Family of membrane bound proteins found adjacent to GPCR Can be stimulatory S or inhibitory i They contain GTPase activity that hydrolyzes GTP Guanosine triphosphate G proteins consist of three subunits heterotrimeric I Alpha 0t Beta B and Gamma y Family of membrane bound proteins found adjacent to GPCR o o consist of heterotrimeric I Alpha 0t Beta B and Gamma y subunits 0 Alpha 0t can be stimulatory Gs inhibitory G1 Gq and G 0 They contain GTPase activity that hydrolyzes GTP guanosine triphosphate O O O O G proteins are present in two states I Active and inactive o In the inactive state I ocBy subunits form a I is bound to the OL subunit I Trimeric complex 0 Ligand binding stimulates the exchange of GDP for GTP 0t subunit dissociates from By subunits Dissociated subunits activate effect GTPase activity hydrolyses GTP G protein goes back to inactive site 0000 0 Three effector systems Effector Second Messenger Adenylate cyclase CAMP Phospholipase C Inositol phosphate Ion channels Ions cAMP cyclic adenosine monophosphate o binds to the receptor and activates a Gs o low concentration of hormone can produce large effect downstream 0 One molecule of hormone interacts With receptor activating one adenylate or adenylyl cyclase Which creates 100 cAMPs o cAMP activates 100 protein kinases o Kinases can phosphorylate 1000s of proteins 0 Inactivation occurs by the action of the enzyme I cAMP is inactivated to AMP I Phosphodiesterase clips the phosphodiester bond Interaction With a stimulatory G protein Gs activates AC Interaction With an inhibitory G protein Gi inhibits AC Inhibition occurs mainly by blocking AC activation adrenergic receptors OOOO Lecture 3 O o A hormone may bind to various types of receptors 0 Epinephrine I Binds to B2 receptors in smooth muscle cells 9 dilation of blood vessels I Binds to on receptors and causes Ca2 movement into cells 9 muscle constriction 9 blood vessel contraction 0 Not a big problem due to receptor distribution I B receptors predominate in skeletal muscle and liver I OL receptors predominate in the viscera and smooth muscles The effector is I Three messenger molecules are produced 0 Diacylglycerol DAG 0 Inositol triphosphate 1P3 0 Ca2 ion o G protein is a Gq type 9 activation of e PLC originates and from the inner membrane 9 uses as second messengers o activates from endoplasmic reticulum o DAG and Ca2 activates PKC resulting in protein phosphorylation I Binding of 0t subunitGTP opens the Ca2 channel I Increase in intracellular Ca2 and release of more Ca2 from ER I Ca2 combines With calmodulin Ca2 binding protein and activates protein kinases calmodulindependent kinases O I Binding of By subunits opens the inward rectifier K channel I K leaves the cell I Hyperpolarization of cells 9 effect of acetylcholine o G proteins I ocsubunit family 0 Gs Gi Gq I By subunits 0 Different B and y subunits o Receptors I Types I Location 0 Effector Systems I Adenylate cyclase I Phospholipase C I Ion channels o Ligand is a molecule that binds to a receptor no only GPCR I Hormones Insulin I Neurotransmitters acetylcholine I Drugs can be more selective e I Agonist positive effect I Antagonist negative effect I Partial Antagonist 12 effect 0 I Relative numbers of receptors I Types of receptors 0 Receptors With positive or negative effects 0 Tissue type 0 These pathways are not only for GPCR o receptor protein goes into the cell I receptor protein is metabolized broken down in the cell I receptor protein is placed back into the membrane 0 o Ligandreceptor complex goes inside the cell by 0 Receptor and ligand are internalized in vesicles called o In recycling the receptor goes back to the plasma membrane to O o Ligandreceptor 0 Receptor and ligand are delivered to for degradation into smaller units 0 Degradation decrease of the number of receptors on the plasma membrane o Kinase domain is in the cytoplasmic region of the receptor 0 undergoes a forming dimers 0 Activation of the 9 autophosphorylation on tyrosine o The kinase activity in the activated receptor phosphorylates intracellular targets enzymes 9 activation or inactivation of target o Lipidsoluble hormones e g steroids bind to cytoplasmic intracellular or nuclear receptors 0 Cytoplasmic glucocorticoid and nuclear estrogen T3 T4 Lecture 4 0 Also called 0 Located at the base of the brain I In a pocket of the sphenoid bone sella turcica just below the hypothalamus 0 Attached to the hypothalamus through the infundibulum or pituitary stalk o It is composed of two regions I or adenohypophysis I or neurohypophysis 0 These regions are anatomically and functionally different o It has three lobes 39 9 Upper lobe 0 It surrounds the infundibulum 9 Intermediate lobe 0 Minimal function in adult humans 0 Releases melanocyte stimulating hormone MSH in some species I 9 Anterior lobe 0 Larger portion 0 Collection of axons from the hypothalamus 0 Part of the hypothalamus 39 0 Contains nerve tracts 39 0 Also called the neural lobe or posterior lobe o Neuronal and vascular connection I Hypophyseal HypothalamoHypophyseal tract 0 Hypothalamus and posterior pituitary connection I Hypophyseal HypothalamoHypophyseal portal system 0 Hypothalamus and anterior pituitary connection o 0 Vascular connections between the hypothalamus and the anterior pituitary o Plexus is a capillary network 0 Anterior hypophyseal veins drain the blood containing hormones into the circulation Hypothalamic hormones Anterior Pituitary hormones CRH T corticotropin releasing hormone ACTH adrenocorticotropic hormone MSH melanocyte stimulating hormone GRH T growth releasing hormone GIH 14 growth inhibiting hormone GH growth hormone TRH T thyrotropin releasing hormone TSH thyroid stimulating hormone GnRH T gonadotropin releasing hormone LH 1uteinizing hormone FSH follicle stimulating hormone PRH T prolactin releasing hormone PIH Jr prolactin inhibiting hormone Pr prolactin Stimulatory T Inhibitory T Cell Type Hormone Somatotropes Growth hormone Corticotropes ACTH amp MSH Thyrotropes Thyroid stimulating hormone Lactotropes Prolactin Gonadotropes Follicle stimulating hormone Luteinizing hormone o types of anterior pituitary 0 Cell synthesize and secrete o Hormones act on other endocrine tissues or systems I Most hormones released from the anterior pituitary are o Tropic hormones stimulate the release of other hormones in a receptormediated and tissue specific manner 0I I By hypothalamic releasing hormones I Levels of secreted hormones from the pituitary andor target organ 0 Stimulatory or inhibitory 0 Can occur at Target Organs Hypothalamus or the Pituitary o ACTH corticotropin is synthesized and secreted by corticotrophs o ACTH is a polypeptide tropic hormone o Often produced with CRH in response to biological stress 0 ACTH stimulates glucocorticoid mainly cortisol secretion by adrenal gland 0 GH is a of about 190 amino acids 0 Hypothalamus releases GHRH that stimulates somatotrophs to produce and secrete GH liver muscle bone and adipose tissue 0 GH has different effects in these tissues I GH stimulates growth in most tissues and is a regulator of metabolism 0 GH binds to its receptor on targets cells in target tissues o Somatomedins 9 hormones that promote cell growth and diVision in response to stimulation by growth hormone Lecture 5 o Mediated by somatomedins also known as insulinlike growth factors IGFs secreted by the liver step 2 GH activates production of somatomedins in liver 0 IGFs act on target cells in target tissues I Growth promoting effects of GH 0 IGF receptors 0 GH promotes the production of two somatomedins in liver I Insulin like growth factor I o Acts on bone I Insulin like growth factor II o Acts on organs and tissues 0 Somatomedins promote cell growth and division in response to GH 0 GH binding promotes dimerization bringing two receptors together 0 Dimerization is important to recruit tyrosine kinases which phosphorylate the receptor 0 There is phosphorylation and translocation of proteins to the nucleus I Activation of gene transcription in the nucleus
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