| 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 |
