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endocrinology: intro, vertebrate endo system, gen mechanism of hormones

Term	Definition
why is endocrinology important?	• understanding development: fertilization -> cell proliferation -> differentiation • integrates developmental events, physiological processes, and specialized secreted chemicals
why is endocrinology important to animal sciences?	• main goal of animal sciences: develop animal that will grow and reproduce at most efficient rate • growth and development is key to this
which body system is integrated with the endocrine system?	• the nervous system • ex. milk letdown: sight of calf, sound of milking machines, or stimulation of udder causes milk to be released into duct system
Berthold's 1849 experiment	• first recorded endocrine experiment: concluded that testes secrete something that 'conditions the blood', influencing a cockerel's body to develop male characteristics • led to discovery of testosterone (isolated/crystallized in 1935)
Von Mering and Minkowski's 1889 experiment	• remove dog's pancreas -> disease we know as diabetes mellitus • eventual recognition of insulin and control of diabetes
Bayliss and Starling's 1902 experiment	• first experiment demonstrating existence of a 'hormone' - Starling coined this term in 1905 • acid ingesta leaves stomach -> secretin released by duodenal mucosa -> secretin travels to pancreas and stimulates discharge of pancreatic juices
two types of gland	• endocrine glands: ductless, secrete directly into the blood (pituitary) • exocrine glands: secretions carried by ducts (sweat gland) • pancreas has both: Islets of Langerhans (endo), acinar cells (exo)
hormones	• secreted by endocrine glands • function in chemical adjustments and regulate activities of other cells thru the body • influence rate of existing rxns which usually involve enzymes
major functions of hormones	• reproduction • growth and development • maintenance of internal environment (homeostasis) • energy production, metabolism, utilization, storage • response to stimuli
homeostasis	• term coined by Claude Bernard after his investigations • organisms maintain a constant internal environment to be more independent of the outside world and preserve the conditions of life
neuroendocrine integration and homeostasis	• extrinsic and intrinsic factors affect physiological processes • sensory cells respond to sensory cues: release hormones/transmit nerve impulse to neuron or cell which secretes chemical messenger
negative feedback systems	• hormone causes production of another hormone to decrease • ex. thyroid hormones slow down production as levels increase
positive feedback systems	• increased concentration of a hormone causes release of a second hormone • ex. oxytocin released in labor causes release of more oxytocin
hormones and behavior	• gonadal hormones -> reproductive behavior; affects success of courtship, mating, maternal behaviors, libido • fetal hormones: presence or absence of testosterone/estrogen, early exposure to stress hormones can program behavior
essential structure of the endocrine system	• network of glands (and some tissues) hat secrete hormones which regulate bodily functions like growth and metabolism • endocrine diseases are common and usually occur when glands produce incorrect amount of hormones
endocrine gland	• composed of prominent mass of secretory cells as well as connective tissue, blood vessels, and nerves • secrete product directly into bloodstream (ductless)
hypothalamus	• region in the middle of the base of the brain, encapsulates the ventral portion of the third ventricle • controls immense number of bodily functions
pituitary gland	• major endocrine organ located immediately below the hypothalamus and brain • produces large number of protein and peptide hormones - often called the 'master gland'
relationship between hypothalamus and pituitary gland	∙ hypothalamus produces releasing and inhibiting hormones that act on the pituitary gland, stimulating the release of pituitary hormones ∙ hypothalamus communicates with anterior pituitary thru hormones and posterior pituitary thru nerve impulses
hormone vs. neurotransmitter vs. neurosecretion	∙ neurotransmitters: chemicals released by neurons -> synapse -> effector cells (short distance), may function as hormones ∙ neurosecretions: hormones produced and released by neurons (ex. oxytocin, vasopressin - long distance action) ∙ overlaps
four structural groups of hormones	∙ peptides and proteins ∙ steroids ∙ amino acid derivatives (catecholamines) ∙ fatty acid derivatives (eicosanoids)
peptide and protein hormones	∙ made of amino acids, chains range from 3 long (TRH) to >180 (HGH) ∙ produced in many glands: pituitary, hypothalamus, pancreas ∙ stored in gland of origin then released into capillaries
steroid hormones	∙ made in the gonads (sex steroids - estrogen) and adrenal gland (adrenal corticosteroids - cortisol) ∙ complex structure using cholesterol as precursor ∙ not stored in significant quantities
amino acid derivative hormones	∙ thyroid hormones: use tyrosine as a precursor ∙ catecholamines: includes epinephrine and norepinephrine, used as both hormones and neurotransmitters
fatty acid derivative hormones - eicosanoids	∙ unique fatty acids with hormone-like properties: prostaglandins ∙ related chemicals that may have physiological roles: thromboxanes, prostacyclins, leukotrienes
endocrine hormone delivery	∙ hormone circulates thru blood to bind to distant target cells
paracrine hormone delivery	∙ diffuses from cell to target cell thru extracellular space
autocrine hormone delivery	∙ feeds back to cell of origin
neurocrine hormone delivery	∙ neuron contacts target cells by axonal extensions and releases hormone into synaptic cleft between the two cells
neuroendocrine hormone delivery	∙ nerve releases hormone into the bloodstream
lumonal hormone delivery	∙ hormone is released into lumen of gut
which types of hormones may circulate bound to carrier/binding proteins?	∙ steroid hormones ∙ thyroid hormones (catecholamines) ∙ some protein hormones
carrier/binding proteins	∙ restrict diffusion through tissues (increase size/change shape), prolong action of hormone by protecting from degradation and elimination ∙ bound hormones can't enter cells: TBG, CBG, albumin, IGFBPs
general hormone action	∙ hormone from gland -> target cell -> receptor -> second messenger systems ∙ signal received -> hormonal response -> reaction
target cells	∙ while most hormones circulate thru the blood and come into contact with all cells, a hormone will only affect a limited number of cells - target cells ∙ a hormone's target cell has receptors for that hormone
receptors	∙ molecular components of cells that provide specificity for hormone-cell interaction ∙ may be component of plasma membrane or cytosolic or nuclear elements; may be bound by agonists or antagonists
agonists vs. antagonists	∙ agonists: bind the receptor and induce all post-receptor events that lead to a biologic effect ∙ antagonists: bind the receptor and block binding of the agonist, NOT inducing intracellular signaling events
cell surface receptors	∙ embedded in the plasma membrane ∙ binds peptide/protein hormones, catecholamines, eicosanoids ∙ generates '2nd messengers' which alter activity of other molecules in the cell - usually enzymes
intracellular receptors	∙ in the cytoplasm or nucleus ∙ binds steroid and thyroid hormones ∙ affects transcriptional activity of responsive genes
types of cell surface receptor	∙ seven helix transmembrane: crosses membrane seven times (GnRH receptor) ∙ tetraheterodimer: made of four parts, two cross membrane (insulin receptor) ∙ single transmembrane: crosses membrane once (EGF)
cell receptor domains	∙ extracellular: resides exposed outside the cell ∙ transmembrane: hydrophobic stretches of amino acids sit in the lipid bilayer ∙ intracellular/cytoplasmic: tails/loops of receptor that are within the cytoplasm
second messengers of hormone action	∙ hormone is the 1st messenger - actions manifest thru production of intracellular 2nd messengers, which affect physiological responses ∙ multiple hormones may use same system, single hormone may use many systems
three major second messenger systems	∙ cyclic nucleotides: cAMP and cGMP ∙ protein kinases may be affected by second messengers or extracellular signals; affects overall signal cascade ∙ phospholipid derivatives and Ca: diacyl glycerol (DG), inositol triphosphate (IP3), arachidonic acid
signal transduction	∙ hormone binds receptor ∙ conformational change occurs in receptor ∙ transduction of signal across membrane to activate 2nd messenger production
cyclic nucleotides and hormone action	∙ hormone binds to receptor in membrane (G proteins) ∙ signal transduction activates adenylate cyclase, which converts ATP to cAMP (second messenger) ∙ cAMP binds and activates protein kinase -> can now function to phosphorylate -> cascade to response
metabolism of cyclic nucleotides	∙ cAMP/cGMP: rapidly metabolized by phosphodiesterases -> 5'AMP or 5'GMP -> dephosphorylate proteins, cell's activity returns to normal ∙ methylxanthines (caffeine, theobromine, etc.) inhibit cAMP/cGMP phosphodiesterases -> promotion of hormone action
G proteins	∙ regulatory proteins in signal transduction of several systems like cyclic nucleotide second messenger systems
G proteins and dual control of adenylate cyclase	∙ hormone binds receptor -> α subunit activates with GTP, βγ subunit may remain associated with membrane ∙ adenylate cyclase (AC) activated by α subunit/GTP to form cAMP ∙ inhibitory G proteins block AC activity -> lower concentration of cAMP
effects of G proteins besides control of adenylate cyclase	∙ activation of ion channels ∙ activation of phospholipases C or A2 ∙ activation of phosphodiesterase
protein kinases and the second messenger system	∙ hormone binds receptor -> conformation change which activates kinase domain in cytoplasmic region of receptor ∙ receptor the phosphorylates itself, then other intracellular targets ∙ ex. insulin and tyrosine kinases
multiple membrane receptors	∙ '3rd messengers' produced from phospholipids: ∙ arachidonic acid (eicosanoid precursor) ∙ inositol triphosphate (IP3) ∙ diacylglycerol (DG/DAG)
G proteins and IP3 and DG formation	∙ hormone binds receptor -> activates G protein -> activates phospholipase c (PLC) ∙ PLC acts on PIP2 -> IP3 and DG, which are messenger molecules
actions of IP3 and DG	∙ IP3 increases intracellular Ca+ ion from endoplasmic reticulum ∙ DG activates protein kinase c, which can increase Ca+ ion into cell from extracellular space ∙ increased Ca+ -> cellular processes like muscle contraction
uses of Ca+ ion	∙ phosphoinositide cascade/Ca+ ion used in: ∙ glycogenolysis in liver ∙ insulin secretion from pancreas ∙ epinephrine and norepinephrine secretion from adrenal gland ∙ smooth muscle contraction ∙ TRH, GnRH
eicosanoids and hormone action	∙ derived from arachidonic acid released by phospholipids within the plasma membrane ∙ hormones/other stimuli may activate phospholipase activity and liberate arachidonic acid for eicosanoid synthesis
arachidonic acid	∙ formed from linoleic acid ∙ multiple membrane messenger molecule
eicosanoids	∙ arachidonic acid may be converted to: PGs, TX, PC, or LTs ∙ cortisone (NSAID) blocks AA release and prevents eicosanoid synthesis ∙ NSAIDS prevent production of prostanoids (PGs, TX, PC) ∙ VitE/C, garlic, ginger, alcohol may modify eicosanoids
prostaglandins	∙ eicosanoids - major role in vascular smooth muscle, inflammation, blood flow to organs, transport across membranes ∙ prostacyclins - inhibitor of blood platelet aggregation, vasodilator, produced by blood pressure wall
thromboxane A2	∙ eicosanoid - product of platelets, causes aggregation, constriction of vascular and bronchiolar smooth muscle
general mechanism of intracellular receptors	∙ lipid-soluble hormone diffuses thru plasma membrane and binds with receptor in cytoplasm ∙ receptor-hormone complex enters nucleus and triggers gene transcription ∙ transcribed mRNA -> proteins -> altered cell activity
structure of intracellular receptors	∙ steroid/thyroid receptors: members of superfamily of transcription factors ∙ receptors composed of single polypeptide chain with three distinct domains
three domains of an intracellular receptor	∙ amino-terminus: interacts with transcription factors ∙ DNA binding domain: amino acids bind to specific sequences of DNA ∙ carboxy-terminus: binds hormone, AKA carboxy-terminus or hormone binding domain
hormone-receptor binding and interactions with DNA	∙ when hormone binds to receptor: receptor activates (changes conformation) and becomes able to bind DNA ∙ activated receptor binds to specific DNA sequence in promotor of hormone-responsive gene ∙ transcription of specified genes affected
permissive action of hormones	∙ some hormones (steroid/thyroid) must be present for other hormones to exert effects - ligands enhance each other's action or action of other hormones working thru membrane receptors
synergism	∙ physiological response to combo of two hormones is greater than the response to either hormone alone (not permissive)
receptor regulation	∙ receptor numbers are not static - constant flux ∙ may change with cell cycle or differentiation ∙ cell may become more or less responsive to certain hormone, or gain or lose the ability to react to specific hormones
hormones regulate receptor numbers	∙ hormone may regulate own receptor (homologous) or other receptors (heterologous) ∙ up-regulation: positive, presence of hormone -> presence of more receptors ∙ down-regulation: negative, presence of hormone -> decreased binding/fewer receptors
termination of hormone action	∙ degraded in blood by enzymes or in organs like liver ∙ steroid/thyroid hormones, RNA, and proteins degraded in cytoplasm ∙ hormone-receptor complexes cluster at sites on membrane -> endocytosis -> degraded by lysosomal or other enzymes
pathophysiology level of hormone levels	∙ syndromes of deficiencies: increased sensitivity to missing hormone, correlated with increased concentrations of receptors ∙ exposing cells to elevated levels: may decrease target tissue receptors, receptor modulation may be important adaptation

Created by: junoreg

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