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Applied Endocrinology
Midterm Material
79
Biochemistry
Undergraduate 4
02/18/2015

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Term
Define hormone
Definition
Regulatory chemical produced in an endocrine gland or scattered cells, secreted into the blood and carried to its target cell that responds by altering its metabolism
Term
Define endocrine
Definition
acts at a distance from the release site
Term
Define paracrine
Definition
acts on nearby cells
Term
Define autocrine
Definition
acts on its own secreting cell
Term
Define neuroendocrine
Definition
synthesized by nervous tissue and carried in the blood
Term
Define neurocrine
Definition
released by nervous cells in contact with target cells
Term
Why should pheromones count as hormones?
Definition
They are essentially hormones that regulate members of a population
Term
What is an additive/concerted response to hormones?
Definition
Two hormones act to increase an activity, and the effects of each contribute the same together as they did separately
Term
What is a non-additive response to hormones?
Definition
Together they produce a positive response but not the added response of both of them
Term
What is an antagonistic response to hormones?
Definition
The positive response of one hormone is cancelled out by another one.
Term
What is a synergistic response to hormones?
Definition
The combined response to two hormones is greater than the two of them put together
Term
What is a permissive response to hormones?
Definition
The combination of two hormones produces a high response despite a non-response from one alone.
Term
What is the range of amounts hormones can be released in?
Definition
10^-6 -> 10^-9 g/mL
Term
Amount of hormone available to target cells depends on what? (3)
Definition
level of synthesis and release, level of biological activity, level of turnover
Term
Properties used to define hormones?
Definition
Produced by specific cells to act on target tissues, hormone levels higher in blood draining gland, determination of origin,reversal of effects, purification of producing cell extract increases potency
Term
What are the two methods by which hormones can control gene expression?
Definition
Regulate gene transcription-->RNA stability, regulate RNA translation-->protein stability
Term
What are the 3 main actions of hormones on cells?
Definition
Control of gene expression, modulate activity, alter cellular transport and membrane permeability
Term
By what methods can hormones alter cellular transport and membrane permeability?
Definition
-intracellular trafficking; transport process, polarity, water permeability; exocrine secretion
Term
Effects of hormones? (8)
Definition
morphological changes, cell division/differentiation, protein synthesis, enzyme regulation, muscle contraction, control of exocrine/endocrine secretion, permeability of water, effect on behaviour
Term
4 classes of hormones? (4)
Definition
-Polypeptides, proteins and glycoproteins
-Steroid hormones
-Amino-acid derivatives
-Fatty acid derivatives or eicosanoids
Term
How are polypeptide based hormones produced, stored and secreted?
Definition
produced by genes, water-soluble, accumulate in Golgi vesicles, secreted by exocytosis
Term
How are steroid hormones produced?
Definition
Stepwise conversion of cholesterol by multitude of enzymes, lipid-soluble, produced and secreted as needed
Term
From which amino acids are amino-acid derivative hormones generally produced?
Definition
Tyrosine and tryptophan
Term
Production of fatty acid derivative hormones?
Definition
Derived from cell membrane phospholipids (arachidonic acid), produced locally, mainly autocrine and paracrine effects
Term
Two methods of post-translational modification?
Definition
Glycosylation:carb chains attached for long term change. Phosphorylation: phosphate attached for short term change
Term
Signal for importing into the nucleus?
Definition
P-P-K-K-K-R-K-V
Term
What is a pro-hormone?
Definition
Protein synthesized as large precursor molecule
Term
Common and different structure of pituitary hormones?
Definition
LH, FSH, TSH: Common alpha subunit, unique beta subunit
Term
How are protein hormones released and why?
Definition
Exocytosis, they are water-soluble
Term
Main synthesis sites of steroid hormones?
Definition
Testis, ovary, adrenal cortex
Term
Main enzymes involved in synthesis of steroid hormones?
Definition
Cytochrome P450 family
Term
Notable characteristics of cytochrome P450?
Definition
-electron transport chain, uses oxygen, has a heme prosthetic group, can serve as a detox agent
Term
5 major classes of steroid hormones?
Definition
Progestins, estrogens, androgens, glucocorticoids, mineralocorticoids
Term
Steps to convert cholesterol to pregnenolone?
Definition
Hydroxylation of C20 and C22, Cleavage between C20 and C22 (stim by ACTH occurs in mitochondria)
Term
Convert pregnenolone to progesterone?
Definition
Oxidize 3 OH to 3 keto group, isomerize delta 5 to delta 4
Term
Convert progesterone to cortisol
Definition
Hydroxylation at C17, C21, C11
Term
Convert progesterone to aldosterone
Definition
Hydroxylation at C11, C21; oxidize C18 to aldehyde
Term
Convert progesterone to androgens
Definition
Hydroxylation at C17, cleavage of side chain, reduce C17 keto to OH
Term
Convert androgens to estrogens?
Definition
Loss of C19 methyl group, aromatization of A ring
Term
Function of eicosanoids?
Definition
stimulate inflammation, regulate blood flow, blood clot formation, affect ion transport, modulate synaptic transmission
Term
Where are eicosanoids produced and from what?
Definition
Cell membrane from arachidonic acid derived from phospholipids
Term
How do NSAIDs affect eicosanoid production?
Definition
Inhibit synthesis via cyclooxygenase
Term
Types of eicosanoids?
Definition
prostaglandins, prostacyclin, thromboxanes, leukotrienes
Term
Role of prostaglandins?
Definition
Act mainly on vascular smooth muscle
Term
Role of prostacyclin?
Definition
Produced in blood vessels, inhibit platelet aggregation
Term
Role of thromboxane?
Definition
Produced by platelets, help blood clot formation
Term
Role of leukotrienes?
Definition
Produced by leukocytes, potent vasoconstrictor and permeability inducers
Term
How is iodine transported into the thyroid?
Definition
Iodide actively transported through follicular cells (I/Na symport)
Term
Structure of thyroglobulin?
Definition
glycoprotein with over 120 tyrosine residues, released in lumen
Term
How does Tgb get iodinized?
Definition
Tyrosine peroxidase (TPO) binds I2 to tyrosine residues on Tgb
Term
What percentage of thyroid hormones do T3 and T4 account for?
Definition
10% and 90% respectively
Term
How do thyroid hormones exit the thyroid?
Definition
Lipophilic-diffuse across basal membrane, interstitial space, blood capillaries
Term
How are monoamines synthesized?
Definition
Modification of tyrosine to dopamine, norepinephrine and epinephrine (tyrosine from diet or conversion of phenylalanine in liver)
Term
What secretes catecholamines and what is the ratio of the 2?
Definition
Adrenal medulla, epinephrine and norepinephrine are 4:1.
Term
Serotonin: derived from? found in?
Definition
Tryptophan; CNS, GI and platelets
Term
Histamine: released by? derived from?
Definition
Basophils and mast cells; decarboxylation of L-histidine
Term
Acetylcholine: results from?
Definition
acetylation of choline
Term
3 major control pathways?
Definition
trophic hormones, nervous stimuli, metabolite levels
Term
Examples of lipophilic and water-soluble hormones?
Definition
Steroid and thyroid; proteins and catecholamines
Term
Examples of specific and non-specific carriers?
Definition
globulins; albumin and prealbumin
Term
Which water-soluble hormone binds to a carrier?
Definition
IGF-1
Term
Where and how are peptide hormones degraded?
Definition
By peptidases such as cathepsin mainly in lysosomes of target cells
Term
Define endopeptidase
Definition
Degrade at specific internal sites
Term
Define exopeptidase
Definition
Degrade from end, one amino acid at a time
Term
Describe the 2 phase process of degradation of steroid hormones in the kidney and liver.
Definition
Phase 1: Inactivation->intro of extra functional groups by cytochrome P450. Phase 2: Increase water soluble-> conjugation to sulfate or glucuronic acid. More water soluble and excreted in urine or in bile salts
Term
Define: sulfoconjugate
Definition
Storage form of steroid hormones
Term
Experimental evidence of cell surface receptors? (5)
Definition
Antibody against receptor blocks signalling, limited proteolysis of intact cells blocks response, coupling of hormones with large molecule to inhibit entry into cell maintains hormone effect, membrane fragments retain hormone binding capacity, solubilization of membrane with detergent permits receptor purification
Term
Receptor type= G-protein 2nd messenger=?
Definition
Adenylate cyclase; cAMP, Phosphlipase C; Ca2+
Term
Receptor type= tyrosine kinase 2nd messenger=?
Definition
Auto-phosphorylation
Term
Receptor type= interleukin family (cytokine receptors) 2nd messenger=?
Definition
JAK-STAT
Term
Receptor type= TGFBeta family (serine kinase receptors) 2nd messenger=?
Definition
SMADs
Term
G-protein structure?
Definition
7 transmembrane helices that change conformation with ligand binding
Term
Experimental evidence for involvement of cAMP?
Definition
Test hormone action by measuring changes in intracellular cAMP, mimic response with exogenous cAMP or its analogues, activate adenylyl cyclase with forskolin to mimic hormone effect
Term
cAMP analogues?
Definition
Dibutyryl cAMP, 8-bromo cAMP
Term
Phosphodiesterase inhibitors?
Definition
Theophylline, caffeine, 1-methyl-3-isobutylxanthine
Term
Experimental methods of studying PLC/Ca/PKC pathway?
Definition
Inhibit PLC with U73122 to block action of hormone, increase intracellular Ca2+ using Ca2+ selective ionophores or liposomes loaded with Ca2+, blocking movement of Ca 2+ using:-chelating agent like EGTA-Ca channel blockers-Inorganic Ca antagonist, Artificially activate PKC with phorbol esters should mimic the effect of hormone
Term
What is Imatinib and how does it work?
Definition
Used in cancer treatment. Competitively inhibits BCR-ABL tyrosine kinase which is required for growth of tumour cells in chronic myelogenous leukemia
Term
Mechanism of tyrosine kinase receptor action?
Definition
Hormone binding causes activation and dimerization of receptors. Kinase domains in monomers are autophosphorylated.
Term
3 classes of tyrosine kinase receptor?
Definition
Class 1: epidermal growth factor, Class 2:Insulin and IGF type, Class 3:Platelet-derived growth factor or nerve growth factor
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