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Endocrinology Introduction
Introduction
65
Physiology
Graduate
01/17/2012

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Term
What is the mechanism of action for neurotransmitters?
Definition
released from axons to transmit from neuron to neuron
Term
What is the mechanism of action for endocrine hormones?
Definition
released from a gland to affect distant tissue(s)
Term
What is the mechanism of action for neuroendocrine hormones?
Definition
released from an axon into blood to affect distant tissue(s)
Term
What is the mechanism of action for paracrine hormones?
Definition
released from cells to affect nearby tissue(s)
Term
What is the mechanism of action for autocrine hormones?
Definition
released from cells to affect the same tissues that secreted them
Term
What is the mechanism of action for cytokines?
Definition
released from cells; may act as enocrine, autocrine, or paracrine
Term
List the general classes of hormones and give one example of each
Definition
Gases - nitric oxide
Steroids - cortisol (glucocorticoids), aldosterone (mineralocorticoids), sex hormones
Amino acid derivatives - thyroxine, epinephrine, norepinephrine, T3, histamine, serotonin
Peptides - insulin, pituitary hormones, hypothalamus hormones, glucagon, parathyroid hormone
Eicosanoids - celebrex, vioxx
Term
What is the method of synthesis for most peptides?
Definition
synthesis from amino acids in rough ER as preprohormones, converted to prohormones, converted to hormones
Term
What is the method of storage for most peptides?
Definition
vesicles in the cell
Term
What is the method of secretion for most peptides?
Definition
exocytosis
Term
How long does peptide hormone activity usually last?
Definition
usually only a few minutes
Term
What is the method of synthesis for steroids?
Definition
synthesized from cholesterol from LDL (in the mitochondria)
Term
What is the method of storage for steroids?
Definition
not stored
Term
What is the method of secretion for steroids?
Definition
they pass through the membrane
Term
What is the method of transport for steroids?
Definition
usually via carrier proteins, though sometimes dissolved in blood
Term
What is the method of transport for peptides?
Definition
usually dissolved in blood
Term
What is the location of receptors for peptides?
Definition
Cell surface
Term
What is the location of receptors for steroids?
Definition
Intracellular or nuclear
Term
What is the duration for steroids?
Definition
usually long - may vary from 20 minutes (aldosterone) to days
Term
What is the method of synthesis for eicosanoids?
Definition
made from arachadonic acid
Term
What is the method of storage for eicosanoids?
Definition
not stored
Term
What is the location of receptor for eicosanoids?
Definition
cell surface
Term
What is the duration for eicosanoids?
Definition
short
Term
What is the method of synthesis for gas hormones?
Definition
(for nitric oxide) made from arginine and oxygen by Ca2+-dependent synthase
Term
What is the method of storage for gas hormones?
Definition
not stored
Term
What is the method of secretion for gas hormones?
Definition
diffusion
Term
What is the method of transport for gas hormones?
Definition
blood soluble
Term
What is the duration for gas hormones?
Definition
short
Term
What is the location for receptors for gas hormones?
Definition
varies based on tissue: sometimes none
Term
How do you determine the rate of disappearance of a hormone from plasma?
Definition
infusion of radioactive hormone until infusion rate is steady; at this point, infusion rate = rate of disappearance
Term
What are the three possible locations of cells receptors?
Definition
Cell surface, intracellular, nuclear
Term
What is the formula for receptor-hormone affinity?
Definition
Kd = ([R][H])/[RH]
Kd - dissociation constant
R - receptor
H - hormone
RH - receptor-hormone complex
Term
Describe the mechanism of intracellular receptors
Definition
Mention: 1. hormone chaperones, 2. binding to promoter (called hormone response element), 3. transcription
Term
Which 2 ligand receptors don't require their ligands to bind to DNA?
Definition
vitamin D and thyroid hormones
Term
Describe thyroid hormone receptor activity
Definition
Mention: 1. receptor bound to DNA, 2. HDAC, 3. when hormone binds HAT switches with HDAC, 4. transcription
Term
Describe G-protein-linked receptor activity
Definition
Mention: 7 transmembrane segments, 2. heterotrimeric GTP-binding proteins, 3. ligand binding, 4. GDP swapped for GTP, 5. subunts part, 6. alpha-GTP activates enzyme
Term
Describe adenylyl cyclase activity
Definition
Mention: 1. produces cAMP from ATP, 2. guanylyl cyclase has some mechanism, 3. often activated by G-protein-linked receptor
Term
State the metabolic clearance rate formula
Definition
MCR = (rate of disappearance of hormone from plasma)/[hormone]
Term
How are hormones "cleared"?
Definition
Hormones are cleared by: 1. metabolic destruction, 2. binding, 3. excretion into the bile by the liver, 4. excretion into the urine by the kidneys
Term
Describe phospholipase C activity
Definition
Mention: 1. may be a target of G-protein-linked receptor, 2. catalyzes breakdown of PIP2, 3. produces IP3 and DAG
Term
What do the products of phospholipase C do?
Definition
IP3 - mobilizes calcium from mitochondria and ER
DAG - activates PKC; lipid portion of DAG is arachadonic acid
Term
Describe the activity of calcium as a second messenger/signal transducer
Definition
Mention: 1. entry may be from voltage or ligand-gated channels, 2. calcium binds to calmodulin, 3. when 3-4 of the 4 binding sites are filled, calmodulin changes configuration, 4. multiple effects, including activation or inhibition of protein kinases via phosphorylation
Term
What are the two ways to detect [hormone]?
Definition
radioimmunoassay and enzyme-linked immunosorbent assays (ELISA)
Term
Why is it so hard to detect [hormone]?
Definition
[hormone] is very small
Term
Which method of [hormone] detection is preferred and why?
Definition
3. ELISA, because it does not involves radioactive isotopes, it has been proven cost effective, and much of it is automated with 96-well plates
Term
Describe ELISA
Definition
Mention: 1. 96-well plates, 2. AB coating, 3. add hormone, 4. add AB2, 5. add AB3 (an enzyme-attached AB), 6. add substrate, 7. use colorimetric and fluorescent detection methods to detect [subtrate]; [substrate] are proportional to [hormone]
Term
Describe radioimmunoassay
Definition
Mention: 1. AB for hormone, 2. add subject's fluid, 3. add radioactive isotoped synthetic hormone, 4. competition for binding site, 5. quantity bound is proportional to [hormone] or [isotoped hormone], 6. isolate AB and analyze radioactive isotope, 7. [isotope] is proportional to 1/[subject's hormone], 8. for quantitative assay, perform with varying [isotope]'s and get a curve to compare to result with patient's [hormone]
Term
Describe receptor tyrosine kinase
Definition
Mention: 1. dimerization, 2. auto-phosphorylation, 3. signal transduction, 4. phosphorylation increased by kinase activity, 5. "cross-talk"
Term
Describe estrogen activity
Definition
Mention: 1. bind to IC receptor, 2. chaperone Hsp90, 3. dimerization, 4. bind to promoter, 5. HAT or HDAC
Term
Describe the mechanism for leptin receptor.
Definition
Mention: 1. passes through membrane once, 2. dimerization, 3. phosphorylation of JAK2, 4. phosphorylation of tyrosine residues, 5. STAT proteins, 6. transcription of leptin target genes
Term
What kind of receptor is the leptin receptor?
Definition
enzyme-linked cytokine receptor
Term
What phosphoylated tyrosine STAT molecules are activated during leptin receptor activation?
Definition
1. SH2 (src homology 2) - related to src from Rous sarcoma virus
2. PTB domain proteins - phosphorylated tyrosine binding domain proteins
Term
Describe the mechanism of ion-channel-linked receptor
Definition
Mention: 1. opens and closes quickly, 2. not saturable, 2. may be voltage or ligand-gated, 4. mostly activated through second messenger if ligand-gated
Term
Describe ACh mechanism of ion-channel-linked receptor
Definition
Mention: 1. hydrophobic groups, 2. conformational change
Term
What is the method of synthesis for amine-derived hormones?
Definition
formed from an amino acid in cytoplasmic compartments
Term
What is the method of storage for amine-derived hormones?
Definition
stored in follicles (thyroid)
Term
What is the method of secretion for amine-derived hormones?
Definition
released from follicles into blood stream
Term
What is the method of transport for amine-derived hormones?
Definition
often bound to plasma proteins
Term
What is the location of the receptor for amine-derived hormones?
Definition
nuclear
Term
What is the duration for amine-derived hormones?
Definition
days to weeks
Term
List the benefits to tyrosine-receptor dimerization
Definition
1. localizes complexes, 2. promotes phosphorylation, 3. stimulates enzyme activity
Term
Give examples of the use of tyrosine-receptor dimerization
Definition
leptin, epidermal growth factor, platelet-derived growth factor, nerve GF, VEGF, macrophage colony-stimulating factor, and insulin (which has a dimer without the need of a ligand)
Term
What are the methods of down-regulation for a hormone?
Definition
1. inactivation of receptors, 2. inactivation of signaling molecules, 3. sequestration of receptor from site of hormone action to inside the cell (temporary), 4. destruction of internalized receptor, 5. decreased production of receptor
Term
Describe cytokine receptor activity
Definition
Mention: 1. no intrinsic enzyme activity, 2. dimerization, 3. kinase recruitment (NRTKs of JAK or Src family), 4. Phosphorylation, 5. SH2 recruitment, 6. signal transduction
Term
Give examples of cytokine receptors
Definition
erythropoetin, IL-2, IL-6, leptin, hGH
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