Endocrinology

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endocrinology

the study of endocrine glands, the hormones they produce and the effects of these hormones

endocrine gland

a ductless gland that releases a hormone directly into the blood

exocrine gland

a duct gland that releases a hormone or hormones

Ernest Starling

1905 coined the term hormone from the greek word to arouse or excite

Hormone

chemical messenger produced by endocrine glands or cells where they affect the activity of these cells

discovery of hormones

chinese discovered goiters due to enlarged thyroid gland, suggested seaweed to help iodine levels

Hippocrates

came up with the idea that humans illness could be caused by an imbalance of the 4 humors

Aristotle

recognized that if you remove the testis from male animals they do not develop the same way as normals

Berthold's experiment

effects of castration and testis replacement found that male roosters did not develop secondary sexual traits

Brown-Sequard

self-administered aqueous extract of dog and guinea pig testies

bayliss and starling

discovered the first hormone, secretin, done with dogs, cutting the nervous system to the stomach to prevent any interaction then placed acid in the stomach and saw hormone projection from the pancreas

Von Mering and Minkowiski

removed pancreas from dogs and noted excess sugar in urine and blood, blood glucose levels rose past absorption rates in kidneys and lead to a high level of sugar in blood

Banting and Best

isolated extract of insulin from dog pancreas and was able to treat diabetes mellitus 1 with pancreantic islet extract

diabeties

run though

mellitus

sweet

earl sutherland

discovery of the second messenger cAMP

Guillemin and Schally

discovered hypothalamic neurohormones that regulate anterior pituitary gland thyrotopin releasing hormone TRH, suggested a link between hormones and light

rosalyn yallow

developed a method of measuring small amounts of hormones radioimmunoassays

bernard

living organizms have an internal state that has to be kept in balance

cannon

coined the term homeostasis

negative vs positive feedback

negative feedback is far more important

calcitonin

helps to regulate calcium if there is to much in the system made by perafolicular cells in pancreaus

parathormone

helps to regulate calcium if there is not enough in a system

neurohormones

chemical messengers produced by neurosecretory neurons that are transported via the blood to garget cells

neurosecreory neurons

specialized neurons that carry action potentials and release neurohormones

neuromodulators

chemical messengers that stimulate or inhibit responses of neurons to neurotransmitters

peptide=growth stimulating factors

peptides that stimulate cell division

neurotransmitters

chemical messengers produced by nerve cells, which are released from the pre-synaptic membrane, diffuse across a synaptic cleft, and bind to receptors of the postsynaptic membrane of a nerve or muscle cell

common neurotransmitters

acetylcholine, dopamine, serotonin

semiochemicals

chemical messengers that carry information to other animals

pheromones

affects conspecifics, intra-specific effects

allelomones

affect other species, inter-specific effects

releaser pheromones

rapid effects

primer pheromones

long term developmental effects

allomone

emiter benefits

kariomone

recipient benefits

chemical messengers

any substance produced by a cell of endogenous or exogeneous origin that affects the physiological activity of another cell

polypeptide hormones

hormones consisting of amino acids that are joined by peptide bonds, may be stored prior to release, released phasicly, transported free in blood

insulin

a two chained polypeptide hormone

thyrotropin releasing hormone

single chain polypeptide hormone with 3 amino acids

human growth hormone

single chain polypeptide hormone with 191 amino acids

oxytocin

single chain with a ring

androgen

steroids with masculinizing effects

estrogens

steroids with feminizing effects

glucocorticoids

steroid that effect carbohydrate metabolism

steroid and thyroid hormones

transported in blood bound to plasma proteins

equilibrium between bounded hormones, free hormones and plasma proteins

k=[HP]/[H][P]

half-life of hormones in blood

time required for half of molecules to be inactivated or cleared from circulation (t1/2)

catecholamine hormones

deactivated by monoamine oxidase (MOA) and/or catecholamine-o-methyl transferase (COMT)

steroid hormones

sulfation and glucornoide formation makes these soluable in water to get out of system

permissive effect

one hormone must be present for another hormone to act (thyroxine required for GH induced brain growth)

synergistic effect

effect of two or more hormones acting together greater than sum of their individual effects

human endocrine glands

most endocrine glands secrete more than one hormone, placenta is a transient endocrine gland in females, thymus gland atrophies prior to puberty in both sexes

hormone receptors

high specificity, hight affinty (low Kd), hormone binding to receptor initiates biological activity

homospecific up regulation

prolactin increases prolactin receptors

homospecific down regulation

insulin decreases insulin receptors

heterospecific up regulation

estradiol increases progesterone receptors

heterospecific down regulation

thyroxine decreases thyrotropin-releasing hormone receptors

G-protein- coupled receptors GPCRs

largest class, bind polypeptide hormones, neurotransmitters, rhodopsins, odorant molecules, single chain of 7 hydrophobic transmembrane domains separated by hydrophilic segments, receptor when bound to hormone couples to G proteins

G proteins

bind guanine nucleotides, guanosine diphosphate (GDP), guanosine triphosphate (GTP), heterotrimers, alpha subunit type determines whether stimulator or inhibitory effects

activation G protein signal transduction pathway

alpha-GTP activates enzymes, opens ion channels, activation of enzymes and opening of ion channels generates second messengers, pertussis toxin inhibits on reaction only for Gi

deactivation of G protein signal transduction pathway

alpha-GTP termed a GTP-switch protein because of its intrinsic GRPase activity, cholera toxin inhibits off reaction

membrane receptors with intrinsic enzymatic activity

receptors with tyrosine kinase activity (RTK), receptors with guanlate cyclase activty, not 7-transmembrane receptors, do not associate with G proteins

receptor tyrosine kinases (RTKs)

tyrosine kinase part of receptor, hormone binding to receptor activates tyrosine kinase, receptor for insulin and epidermal growth factor

receptor with guanylate cyclase activty

guanylate cyclase part of receptor, receptor for atrial natriuretic factor (ANF)

receptor with guanylate cyclase activity

guanylate cyclase part of receptor, receptor for atrial natriuretic factor ANF

tyrosine kinase-associate receptor

tyrosine kinase not part of receptor instead non covalent associated, hormone binding causes formation of dimeric receptor that activates tyrosine kinase in cytoplasm, receptor for GH, prolactin, erythropoietin, cytokines such as interferons

cyclin adenosine monophosphate cAMP second messenger

hormone-receptor binding increases adenylate cyclase activity, adenylate cyclase converts ATP to cAMP second messenger, cAMP activates cAMP-dependent protein kinase PKA, PKA phosphorylates proteins

deactivation of cAMP second messenger

cyclin AMP phosphodiesterase converts cAMP to inactive AMP, phosphodiesterase inhibited by methyl xanthines

cyclic guanosine monophosphate cGMP 2nd messenger

transmembrane form as well as soluble form of gyanylate cyclase, cGMP inactivated by cGMP phosphodiesterase

calmodulin

cellular calcium receptor in all eukaryotic cells, four ca2+ binding sites, structurally similar to troponin c, biologically activated when calcium binds to at least three of the four calcium binding sites, activates Ca2+ calmoduline-dependent kinase, stimulates ATPase that pumps Ca2+ out of cells or into storage depots (mitochondria and smooth ER), activates myosin light chain kinase in smooth muscle

Cyclooxygenase1 inhibitors

basal, nonsteroidal anti-inflammatory drugs (NSAIDS), aspirin, ibuprofin, indomethacin

COX2 inhibitors

induced, selective inhibitors (COXIBS), celebrex, vioxx

COX3

brain, tylenol

5-lipoxygenase inhibitors

singulair, treatment of asthma and allergies

prostaglandins

affect smooth muscle activity, increased PGF2alpha: contractions, increased PGE2: relaxation

prostacyclins

inhibit blood platelet aggregation, syntesized by endothelial cells of blood vessels, travel to platelets and decrease free Ca2+

thromboxanes

stimulate blood platelet aggregation, synthesized by blood platelets, clotting stimuli such as thrombin stimulate synthesis, increase free Ca2+ and change platelet shape

leukotrines

increase smooth-muscle contraction, blood vessel permeability, and mucosus secretion in airways, synthesized and released by leukocytes, components of inflamatory response

labor

increased PGF2 alpha, associated with onset, PG inhibitors help prevent premature labor, increased PGF2 alpha decreased bleeding from umbilical cord

abortion

intrauterin devises increase PGF2 alpha

dysmenorrhea

painful menstrual crams, excess PGF2 alpha synthesis, treat with PG synthesis inhibitors

ductus arteriosus

closes at birth in part because of decreased PG exposure, PG inhibitors used to close duct in premature infants

blood clots

to much thromboxane and or to little prostacyclin increases tendency of blood to clot, asprinin is an effective treatment because thromboxane synthesis inhibited more than prostacyclin synthesis

inflammation of arteries

excess leukotrines synthesis causes inflammatory response in arterial wall, treat with leukotrine synthesis inhibitors

stomach ulcers

PG required for normal mucus production, PG treatment to health stomach ulcers

asthma and allergies

leukotrines case contraction of small airway passages in lungs, singulair to treat asthma and allergies

intracellular receptors class 1

receptors of steroid hormones, located in cytoplasm or nucleus, associated with heat shock proteins HSPs when not bound to ligand, when bound to hormone form homodimers that bind to hormone response elements HRSs

extripation and replacement

classic method removal and replacement

ectopic site

site other than normal site

monoclonal antibodies

antibodies produced from hybridomas

hybridomas

formed by cellular fusion of a beta lymphocyte and a myeloma, large amounts of specific antibodies obtained from hybridomas

chemical ablation

use of chemicals or drugs to destroy endocrine function, alloxan or streptozotocin to destroy beta cells o islets of langerhands

hematoxylin

basic dye, interacts with acidic cellular components

eosin

acidic dye, interacts with basic cellular components

bioassays

study of hormonal action in living systems

pigeon crop assays for prolactin

epithelial cell height positively correlated with PRL levels, determine PRL levels using dose-response curve

friedman test

rabbit test for human chronic gonadotropin (hCG), urine from women suspected for being pregnant injected into female rabbit, if woman is pregnant, hCG stimulates rabbit ovaries to form corpora lutca, antibody test for hCG now used

toad bladder/frog skin response to arginine vasopressin (AVP)

use to study mechanism of action of AVP on movement of water across membranes

agonists

mimic action of hormones, diethylstilbestrol (DES), an estradiol (E) agonist

antagonists

inhibit action of hormones, tamoxifen, and E antagonist in breat tissue

autoradiography

method that uses radioactive labeling to determine anatomical location of hormones

immunocytochemistry

antibody-based procedure for visualizing location of substance, antibody to substance of interest conjugated to a fluorescent dye or enzyme

C-fos gene

expression in hippocampus an immediate early gene

c-fos protein

a transcription factor expression in hippocampus

insulin

lowers concentration of glucose in blood

glucagon

raises the concentration of glucose in the blood

radioimmunoassay

curves are inverse, the higher the viral count the lower the testosterone levels

enzyme immunoassay

quantitative measurement of hormones, hormone labeled with enzyme rather than radioactive isotope

spectrophotomer

used to measure bound labeled hormone as indicated by color change caused by enzyme reacting with added substrate

hybridization

annealing or paring of complementary strands of nucleic acid

blot test

determine whether particular nucleic acid or protein present, tissue homogenized and cells lysed with detergent homogenate placed on introcellulose filter, filter incubated with labeled complementary nucleic acid or protein antibody

in situ hybridization

percise cellular location of RNA or DNA of interest, hybridization of labeled probe occurs within cell

antisense oligonucleotides

a method to inactivate specific mRNAs

morpholino oligos

a synthetic form of antisense oligonucleotides

RNA interference (post transcriptional gene silencing)

injection of double stranded RNA to silence specific genes by interfering with their mRNA, dsRNA digested by enzyme to small interfering RNAs (siRNAs)

vertebrate transgenic animals

gene introduction from one species to another, rat GH gene transferred to mice

knockout gene method

disruption of natural occurring gene

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