Exam 3 Bio 225-- Jill Haenfler

6 classes of chemical messengers - each can be defined as...

- Peptides/proteins - Steroids - Biogenic amines ^^ most important + vertebrate hormones - Lipids - Purines - Gases The messengers chemical nature and properties influences the release, transport, and reception mechanism Each is either hydrophillic (can not diffuse through membrane) or hydrophobic (can diffuse through membrane)

Different amplifier enzymes alter the amount of secondary messengers, these 4 messengers are... (amplifier enzyme= enzymes activated by GPCR's to releases a secondary messenger)

- cGMP: Synthesized from GTP by Guanylate cyclase... cGMP will activate PKG which has downstream effects. - Ca2+: Binds to calmodulin and activates PKC - Phosphatidylinositol (IP3)/ Diacylglycerol (DAG): Made from PI(4,5)P2 being cleaved by PLC (more on next notecards) *Gq pathway* - cAMP: Made by Adenylate cyclase converting ATP to cAMP... Phosphodiesterase (PDE) decyclizes cAMP to AMP *(Gi/Gs pathway)*

Receptor enzyme pathway for Guanylate cyclase... example of this??

1. Ligand binds receptor causing conformational change traveling down transmembrane domain activating the catalytic GUANYLATE CYCLASE domain 2. Converts GTP to cGMP (cGMP acts as a secondary messenger) 3. cGMP binds to protein kinase G which phosphorylates target proteins like serine or threonine Example: ANP ligand which is released from the heart and controls blood volume! - ANP = atrial natriuretic protein

All biological actions of corticosteroids

1. Long term stress response on previous notecard via glucocorticoids Other biological effects: 2. Function in other electrolyte balance: Conservation of salts Mineralocorticoids cause us to store more salts and release K and H 3. Developmental roles! Important for lung maturation and making sure surfactant is being produced!!! - Babies are in amniotic fluid with no lung function so when they are born we NEED them to cry once saying their lungs inflated and the second time means they can inhale and also can exhale meaning their surfactant (provide decreased surface tension to prevent too high which results in collapsed lung) prevent the lungs from sticking together and so they can inhale/exhale properly. ***Sudden death syndrome: Baby inhales, upon inhalation lungs deflate and stick together so they cannot breathe.

Lect 25 (new professor in recordings) - what 2 categories of endocrine systems exist? - properties of neuroendocrine, what are neuroend. cells?

1. Neuroendocrine system: The endocrine system communicating with the brain for us to communicate with our sensory system a response to a stimulus. - Hypothalamus, Pineal Gland, Pituitary Gland a. Most ancient endocrine system b. Some neurons modify and assume secretory function (hypothalamic neurons) c. Links outside environment to neuron system to endocrine regulating factors. Neuroendocrine cells are cells in the endocrine system (such as hypothalamic neurons) that release hormones (neurohormones) into the bloodstream which will cause a response 2. Peripheral endocrine system: Organs in the peripheral body - Thyroid, parathyroid, adrenal, gonads, pancreas

Actions of the thyroid hormones T3/T4

1. Somatic growth and differentiation 2. Brain development and differentiation *Note: if a fetus had low thyroid levels they would come out short stature AND with mental retardation* as the hormone regulates cell differentiation of muscle/bone tissues and the brain! 3. Metabolism: regulates the number of Na/K pumps inserted in the plasma membrane 4. Thermogenesis: heat production/temp regulation 5. Calorigenic: calories used in digestion/metabolism 6. Breathing rate: Regulates oxygen consumption and respiratory metabolism which lead to how fast/slow we breathe 7. reproduction 8. Hair growth in mammals and molting in birds 9. Metamorphosis of amphibians

More in depth peptide pathway END where peptide hormone leaves the cell and finds its target

1. The peptide hormone AVP/vasopressin that exited via exocytosis will travel by diffusion or (since they're hydrophilic) circulatory system/blood stream. 2. The AVP then will bind to the transmembrane receptor proteins and cause conformational change which then causes signaling/initiates signal transduction 3. Rapid effects on the target cell (target cells have short half-life (point at which 50% of product remains) from seconds to hours before broken down) 4. Signal cascade ends when proteolytic enzymes break up the AVP or chemical messenger attached to the receptor cell.

More in depth peptide pathway AND on the next notecard is what happens once it leaves the cell and finds its target

1. hydrophillic protein/peptide transcribed from mRNA on the rough ER into the preprohormone (synonymopus to polypeptide) 2. The rER releases the preprohormone through a vesicle and in that vesicle its first cleavage occurs to the prohormone 3. The prohormone travels to the Golgi apparatus where it is packaged and released and stored in the SECRETORY vesicle 4. Before exocytosis, the second cleavage occurs in the secretory vesicle from prohormone to the active hormone messenger. Ex using vasopressin! Vasopressin is made in advance (hydrophilic) 1. Transcribed from mRNA into polypeptide/preprovasopressin at rough ER which is inactive 2. The signal peptide (responsible for helping the cell to sort the peptide!) is first cleaved in first secretory vesicle at the rough ER from preprovasopressin to provasopressin - still usually inactive molecules! 3. The provasopressin is packaged in the golgi and stored in the cell membrane 4. Before exocytosis, the provasopressin is cleaved again (AVP is cleaved off) and AVP (aka vasopressin) becomes the active hormone which exits via exocytosis.

Iclick question, which saturates at lowest [ligand]? - log plots...

A since it has lowest Kd means takes lower concentration of ligand to saturate receptor and also has high affinity for ligand. - Semilogarithmic plots may be used... they still show Kd (see where ligand bound to receptor is at 50% and then look at the x value... 10^0 (1), 10^1, 10^-1) - 10^-1 is lowest Kd which means highest affinity!

More in depth on Adrenal Medulla and Short term stress response...

Adrenal medulla/short term stress: - The adrenal medulla is regulated by and connected to the central nervous system - any short or long term stress response is referred to as the general adaptation syndrome (three stage response to stress: alarm, resistance, exhaustion) Pathway 1. Produces a fight or flight response through first perception of the threat 2. Hypothalamus stimulates the release of epinephrine and norepinephrine (adrenaline/noradrenaline) 3. Hormones will be transported through the circulatory system binding all over allowing us to better deal with the stressor... 4. Liver will breakdown glycogen to provide glucose for our cells to use... Increased respiration and heart rate means increased oxygenation along with faster heart beats so cells get oxygen faster and more frequently

Pathway of hormones from hypothalamus regulating the pituitary gland (separated by anterior/posterior)...

Anterior Pathway: Hypothalamic hormones in the hypothalamus are stimulated and secrete neurohormones to the *hypothalamus pituitary portal system* which travel then through the hypothalamus pituitary portal system capillaries which are dispersed throughout the anterior pituitary gland stimulating all target cells. The cells then release anterior pituitary hormones that travel to the pituitary vein (stems from both anterior and posterior pituitary structures) and will be delivered to the entire body. - Travels through two capillary beds! Posterior Pathway: Hypothalamic hormones are stimulated and their axons are longer and connected closer to the posterior pituitary cells. These neurohormones which are called posterior pituitary hormone are STORED in neurosecretory vesicles before being secreted into blood stream/picked up by posterior pituitary vein and combining with the anterior pituitary vein and those hormones. - *hormone released by hypothalamus is given new name (post. pituit. hormone) but this hormone from the hypothalamus directly goes into the blood stream to take effects* - Projects allll the way into the posterior pituitary to release hormones!

Posterior Pituitary Hormones... - ADH

Anti-diuretic Hormone: Causes kidney tubules to insert more aquaporins into the epithelial cell wall to increase reabsorption (prevent secretion) of water during dehydration. - Regulated by osmolarity levels - Made in posterior pituitary and travels (endocrine) thru blood stream to kidneys

Hormone-Ligand receptor interactions explaining thyroid issues... Autoimmune disorder... goiter in antagonist?

Autoimmine disorder of the thyroid where the immune system produces antagonists OR agonists to the TSH hormone... antagonists-- hypothyroidism Antagonist will bind to the TSH receptors and block TSH which also means the antagonist will not produce any response! Therefore, the thryoid will never be stimulated and T3/T4 levels will be LOW... This causes feedback to increase TRH and increase TSH but TSH just accumulates and antagonists stay bound to the TSH receptors. Goiter will not occur because TSH receptors are not stimulated and causing any downstream effects on the thyroid gland. - Low T3/T4 - High TSH - NO GOITER Graves disease: hyperthyroidism Agonists made by the body bind to the TSH receptors which induces a respond downstream causing the thyroid gland to be stimulated and produces T3/T4... This in turn will cause negative feedback decreasing TRH and TSH, HOWEVER, the agonist is not effected by negative feedback and stays bound to the TSH receptors causing very high T3/T4 constant synthesis and low TSH. - High T3/T4 - Low TSH - Can have goiter

Second class of messengers begins 2: Biogenic amines - All the different types of aminos and examples thyroid hormone properties...

Biogenic Amines: Contain an amine group (-NH2) - derived from single amino acids... - Mostly hydrophilic and for vertebrates - Some are true endocrine hormones and some are neurotransmitters (synapses) Tryptophan derivatives: Serotonin (neurotr) and melatonin Tyrosine derivatives: - Catecholamines (dopamine (neuro), epinephrine, norepinephrine) - Thyroid hormones T3 and T4 (true endocrine hormones) which are HYDROPHOBIC and diffuse readily across membrane - Octopamine and tyramine (both neurotr) Histidine derivatives: histamine

Thyroid Gland other hormones produced... - Two cases Adults need it: - produced by? - Regulation

Calcitonin!!! - Produced by C-cells in the thyroid gland - Regulate levels of calcium in the blood - *Hypocalcemic*: Lowers Ca levels in the blood - Lowers Ca in blood through 3 mechanisms... - 1. Stimulates excretion of Calcium in the kidneys - 2. Stimulates bone mineralization (Building up of bone through absorbing Ca - 3. Decreases absorption of calcium from our food in our small intestine Two cases Adults need it: - Calcitonin not important in adults unless the adult is starving since it will help reduce amount of bone mass lossage or if a women's pregnant since the mother would have to compete with the baby for Ca Regulation pathway: 1. Blood Ca levels at homeostatic levels (10 mg/ 100mL) rise 2. Rising blood Ca levels stimulates C-Cells in thyroid glands 3. Thyroid glands produce calcitonin which acts to stimulate all three mechanisms (small intestine, bone uptake, excretion) 4. Blood Ca levels lower and homeostatic levels are achieved

Biosynthetic pathways are used for Biogenic Amine formation!

Catecholamines synthesis pathway: catecholamines (Dopamine first, NE, then EPI) are all synthesized in the same pathway (in the order in previous parenthesizes) and they are synthesized within the cytosol of the cells as FREE tyrosine which uses different enzymes Thyroid hormone synthesis: The tyrosine that generates the hormones is a tyrosine attached (BOUND) to a protein thyroglobulin so T3 and T4 get synthesized on the protein and then must be cleaved to be further processed by other enzymes. T3 is made which can be further processed into T4.

Hypothyroidism Thyroid Disorders... - Goiter - CRETINISM - Myxedoma

Cretinism: hypothyroidism disorder where the fetus/baby in the womb has low T3/T4 levels which results in a non-fully developed brain and somatic tissues so there is short stature and mental retardation.

Adrenal Medulla Versus Adrenal Cortex which is immediate stress response? Hormones involved?

Developed by different germ lines in development... 1. Adrenal Medulla: Derived from the ectoderm, function much like postganglionic neurons but are endocrine cells. - Central core that produces catecholamines (Epinephrine and norepinephrine) - controls metabolism, thermogenesis, and cardiovascular activity - *short-term stress response* 2. Adrenal Cortex: Derived from the mesoderm - gonads grow here in fetus - surrounds medulla and produces STEROIDS... (corticosteroids) - Acts through nuclear receptors (I believe this means intracellular receptors so its hydrophobic). - Actions in intermediary metabolism, osmoregulation, development, and stress response - Acts as a *Long-term stress response* system

What can go wrong (insulin)? - Diabetes Mellitus - Type 1 (properties +autoimm.) - Type 2

Diabetes Mellitus: "Sweet urine" Type 1: Insulin-dependent diabetes - Less common, occurs when the body does not produce its own insulin so blood glucose is high... treated with insulin injections - Autoimmune disorder: Can be a autoimmune disorder where antibodies made by the immune system attack Beta-cells of pancreas so no insulin can be produced. Type 2: Insulin-independent diabetes: "life-style disorder" - MOST common, occurs due to inadequate diet, eating all the time (too frequently), an ADULT onset (or in kids, but not born with it) - Due to non-responsive receptors/desensitization - Can be caused by a receptor mutation or more commonly years of unhealthy habits (diet and exercise-- exercise helps spend energy/glucose so levels can normalize) Both have symptoms of being tired with a lack of energy and sweet tasting urine!

Different types of cell signaling Direct or indirect?

Direct signaling: Target cell and transmitting cell are in physical contact... gap junctions - Integral membrane proteins physically interact on adjacent cells is another example Indirect signaling: Chemical messenger travels short or long distances... - Uses circulatory system - Neurotransmitters - Nervous system signal propagation (Box 2 has autocrine and paracrine signaling)

Different types of cell signaling Short to long? - neurohormones - diffusion

Direct/indirect signaling: Direct signaling -> Autocrine -> Paracrine -> Endocrine -> inter-individual Neuronal signaling: Gap junction -> Synaptic cleft (neurotransmitters) -> AP propagate down a cell... there are messages released via neuron signaling that travel through the blood stream called NEUROHORMONES (like vasopressin) Direct signaling: Gap junction or direct contact Indirect signaling... Autocrine: Transmitting cell releases chemical messenger that targets itself via diffusion Paracrine: Signal diffuses from original cell to a nearby target cell via DIFFUSION ENDOCRINE: Signals travel to distant targets through use of the circulatory system inter-individual: signals between different people often through the use of pheromones

Determining the factors influencing receptor/ligand affinity...

Dissociation constant (Kd): The concentration of ligand required for half of the receptors to be bound - High affinity receptors mean less ligand needed to bind receptors so they have lower Kd - Low affinity receptors have higher Kd because it takes more ligand to bind to receptors which attract them less strongly (see graph) Kd is not constant for a ligand/receptor pair but rather is affected by environment so can be altered (ex will be talked about later between oxygen and hemoglobin)

Development of tissues...

Ectoderm: Skin, neurotransmitters Mesoderm: Bones, muscles, blood, gonads (some steroid hormones), amino acids Endotherm: Digestive tract, protein peptides, organs

Start Periphery Endocrine glands!!! - *ENDOCRINE PANCREAS* - Thyroid - C-cells - Parathyroid - Adrenal cortex + Medulla

Endocrine pancreas: Islets of Langerhans cells (made up of alpha and beta cells) make hormones that they relese into the blood stream to travel around the body - ex. Insulin! - NOT exocrine pancreas which involves duct and digestive enzymes!

Pancreas as both exocrine and endocrine... - Islet cells - Enzymes

Exocrine: Releases digestive enzymes into the small intestine via pancreatic ducts to aid in digestion Endocrine: pancreatic Islets release insulin and glucagon which enters surrounding blood vessels

Endocrine vs exocrine signaling

Exocrine: Secrete substances to external surfaces through the use of DUCTS - Examples: digestive enzyme release via pancreatic duct, respiratory tract (interacts w external environment), sweat Endocrine: Long distance cell communication using hormones that travel through the blood stream - Release substance into EXTRACELLULAR FLUID (usually circulatory system) - DUCTLESS - Insulin/glucagon into bloodstream

Labeling the pituitary/hypothalamus... - paths of anterior/posterior pituitary

Functions/general: - Hypothalamus regulates the pituitary gland! - Pituitary gland: Anterior and posterior structure... - Anterior structure acted on by hypothalamic hormones delivered through the pituitary stock/hypothalamus pituitary portal system. - Posterior structure is in direct contact with the hypothalamic neurons which then release posterior pituitary hormones into the pituitary veins Parts: - Pituitary gland connected at the pituitary stock - Pituitary artery from heart connects to stock - Capillary branches starting at the pituitary stock from pituitary artery are called the Hypothalamus pituitary portal system - Anterior pituitary - Posterior pituitary - Pituitary vein

Different amplifier enzymes secondary messengers... MORE on inositol-phospholipid pathway (IP3 and DAG (basic pathway))

G(alpha)q pathway: 1. Ligand binds to receptor and causes conformational change 2. G(alpha-q) subunit separates from the beta/gamma complex and activates Phospholipase C (PLC) which cleaves PIP2 into IP3 and DAG functional subunits. 3. IP3 and DAG go on their sepearte pathways to signal in the cell... on next notecard more details...

Lec 24 cont (next lec) Receptor 3: GPCR properties and pathways - GPCR properties - G-protein properties

G-coupled receptor proteins: releases the "primary messenger" GTP - 7 transmembrane domain proteins - Extracellular face for ligand binding, transmembrane domain to transmit signal and cytoplasmic domain which is connected to the G-protein. G-protein: - HETEROTRIMERIC (3 subunits)... - alpha: nucelotide binding site (ATP/ADP) which hydrolyzes GDP to GTP and vice versa - beta and gamma: tightly bound together, they are released when Alpha is activated.

Different amplifier enzymes secondary messengers... cAMP formation and degradation plus pathway

Gi/Gs pathway uses AC and PKA Uses the Gi/Gs pathways!!! - Adenylate Cyclase converts ATP into cAMP - Phosphodiesterase deactivates cAMP by converting it into AMP Gs-- 1. Ligand binds and activates G(alpha s) g-protein 2. Gs will dissociate from beta gamma complex and activate Adenylate cyclase 3. Adenylate cyclase (amplifier enzyme) converts ATP into secondary messenger cAMP 4. cAMP will activate PKA which will phosphorylate target proteins 5. Serine/threonine *phosPHATASE acts to dephosphorylate these proteins* once the job is done Gi-- 1. Ligand binds and activates G(alpha i) g-protein 2. Gs will dissociate from beta gamma complex and DEactivate/inhibit Adenylate cyclase

Lec. 27 start... Glucagon - made by, released when, anatg eff.? - three routes of influence route... Synergistic actions........

Glucagon: - Made by ALPHA cells - Technically an anabolic hormone but really does more catabolism - *Released in response to Low blood glucose* - glucagon and insulin have antagonistic effects - Is a HYPERGLYCEMIC hormone, breaks down glycogen stores Three methods of action... - Glycogenolysis: Break down of glycogen stores to produce glucose - Lipolysis: Break down of fats into glucose - Gluconeogenesis: Break down of carbon-based molecules like protein in order to produce glucose Decreased blood glucose -> Alpha cells in pancreas triggered to make glucagon -> Glucagon causes its methods above which will increase blood glucose... This results in negative feedback since blood glucose levels will increase. Synergistic actions: Hormones who do not effect each others levels but induce the same response... Cortisol, epinephrine, and glucagon ALL raise blood glucose!

Hypothyroidism Thyroid Disorders... - GOITER - Cretinism - Myxedoma

Goiter: Specifically refers to the enlarged/bulging thyroid gland due to excess TSH - Excess TSH causes constant thyroid stimulation which will cause Thyroid Mitosis and enlargement (goiter) - Hand in hand with hypothyroidism since low levels of T3/T4 usually result in high TSH production and concentrations! Goiter is explained by a malfunctioning thyroid which has low iodine levels... With low iodine levels, T3 and T4 cannot be produced so levels are always low which induces hypothalamus to increase TRH-> pit TSH production and TSH constantly stimulates thyroid with no end since T3/T4 have no negative feedback contribution, only TSH.

Different amplifier enzymes secondary messengers... MORE on inositol-phospholipid pathway (IP3 and DAG (IN DEPTH pathway))

Gq is paired with PLC and PKC! Ligand binding -> Activate G(alpha-q) -> Activate PLC -> Convert PIP2 into IP3 and DAG.... IP3 pathway: 2 different effects 1. IP3 will bind to Ca channels in the endoplasmic reticulum (ER) and causes Ca release into the cytoplasm which will bind Ca2+-calmodulin and ALSO *help DAG activate PKC* 2. IP3 will be phosphorylated into IP4 and have downstream cellular effects DAG: 1. DAG will be made by PLC cleaving and will activate PKC pathway (with Ca2+ from IP# pathway's help) which will phosphorylate and activate many target protein sequences.

Hyperthyroidism Diseases - Graves Disease

Graves disease is an autoimmune, hyperthyroidism disease condition where the thyroid gland is targeted by the immune system. Specifically, antibodies produced will target and attack the TSH receptors on the thyroid gland (acting as agonists) causing stimulation and release of Thyroid hormones. - In extreme cases, eyes bulge out - Treatment includes an antithyroid drug or surgery. Binds to TSH receptors and stimulates

Growth Hormone special cases/malfunctions... ?: which of the following occurs with child born with a GHIH mutation?

Growth hormone surplus... - Gigantism: Increases growth hormone levels EARLY in life... grows in proportion! - Acromegaly: Increased growth hormone LATER in life... most of bones are sealed so can't grow, only the ends grow so features WIDEN and not proportional growth -*Issue!:* Unproportional growth occurs in all muscles... including the heart so a widening heart leads to cardiac conditions Growth hormone Deficiency... - Dwarfism or short stature: Caused by either low levels of growth hormones or decreased receptor sensitivity. ?: answer= gigantism

Begin all ANTERIOR pituitary hormones... - Growth hormone

Growth hormone: Hypothalamus releases GHRH or GHIH... pituitary is stimulated or inhibited to release GH... properties: - Dual regulation (GHIH and GHRH) to maintain homeostatic levels and not overgrow - More important at younger ages - Has direct (causing mitosis and bone growth itself) and indirect (IGF's cause bone growth/mitosis) endocrine effects - Causes growth that is proportional!!! Growth hormone three pathways of action: 1. Growth hormone DIRECTLY acts to metabolize fat cells to use the energy in order to grow.. explains why kids are skinny 2. Growth hormone will directly act on liver target cells to secrete IGFs... IGF's then act as an INDIRECT action from GH to circulate the body via bloodstream and activate all target cells (HIGHWAY). 3. Growth hormone will directly act on somatic tissues (muscles) which produce IGF's that act as an INDIRECT effect of GH LOCALLY (self/neighboring cells) via paracrine and autocrine signaling to induce muscle growth. *IGF's: Insulin-like growth factor* are made in response to GH stimulating organs... nearly every cell in body has an IGF receptor... is present more in kids during growth - adult levels decline

Hydrophobic vs hydrophillic... reminder which type (phobor philic ) each chemical messenger is and what type of receptor do phobic vs philic involve at the target cell?

Hydrophobic: Transmembrane receptor or more commonly and intracellular receptor Hydrophilic: Only transmembrane receptor So far... Hydrophilic messengers include most of the biogenic amines and the peptide hormones Hydrophobic messengers include thyroid hormone T3 and T4 (under biogenic amine categories) and Steroid hormones

Begin all anterior pituitary hormones... - Gonadotropins

Hypothalamus releases gonadotropins which stimulate release of... (Both males and females have) Gonadotropin stimulated hormones... Released by anterior pituitary!... - LH: Luteinizing Hormone - Follicle Stimulating hormone (FSH)

Lec 26 start... - What effect does increasing LH have on testosterone? - What effect does increasing testosterone have on LH?

Increasing LH increases T Increasing T DECREASES LH

Feedback control of endocrine secretion... For all releasing hormones! (ex. using TRH) type of feedback?

Increasing hypothalamus releasing hormone will increase the amount of thyrotropin-releasing hormone, TRH, present (or any RH) which then increases TSH (or any Pituitary hormone) which increases the thyroid gland production of T3/T4 which will have effects on the body but ALSO... the T3/T4 act to inhibit TRH and TSH production which will lower the T3/T4 levels. Now sensing low T3/T4 levels, the TRH and TSH levels rise which increases T3/T4 which inhibit and bring levels back down... this is a continuous loop NEGATIVE feedback cycle.

Overall Anterior Pituitary Hormone venn diagram from book with all hormones present and Overall hormones type and properties (phillic vs phobic)

Insulin: Made through tyrosine kinase... Peptide hormone... hydrophobic Glucagon: Made through cAMP pathway (Gs/Gi)... peptide hormone... hydrophobic Pineal gland: produces hormone from the neurotransmitter serotonin (likely hydrophilic since its a biogenic amine) ACTH: Releases corticosteroids which are hydrophobic Thyroid hormones: T3/T4 are hydrophobic

Endocrine pancreas Insulin control... properties Functions the TWO regulators (on next, next notecard) pathway on NEXT notecard

Insulin: aka hypoglycemic hormone, the "key" to the cell which unlocks it and lets glucose flow in - Hypoglycemic: End effect is lowering blood glucose - Produced by beta cells - Causes cells to insert glucose permeases into cell membrane to allow entry via facilitated diffusion of glucose into cell... Amino acids and fat also up-taken by cell Other functions of Insulin:... 1. Stimulates anabolism: Promotes lipogenesis and glycogenesis (make fat and sugar stores) 2. Inhibits cellular catabolism Ends via negative feedback loop when blood glucose lowers after insulin release. Regulators... 1. The digestive tract stretch receptors trigger brain to produce insulin in pancreas (ANY FOOD, regardless of what it is) 2. Blood glucose levels

Another property of intracellular receptors and responses... (transcriptional cascade)

Intracellular receptors initiate transcription cascades (amplification effect of transcription factors) which means one ligand receptor complex can effect many, many genes and biochemical pathways and cellular functions. - Intracellular receptor activated and binds to DNA which will eventually encode a transcription factor which can regulate many other DNA sequences/activate many other DNA pathways.

Hormone receptors 1: - Intracellular receptor: Properties and pathway - examples of reglatuion

Intracellular receptors: regulate TRANSCRIPTION (in nucleus) of target genes - Are only for HYDROPHOBIC ligands so they diffuse through membrane - Have at LEAST 2 domains: A. The ligand-binding domain B. The DNA-binding domain (C.) often has a regulatory domain: cytosol receptors could have a regulatory domain prventing entering into nucleus... nucleus receptors could have regulating domain preventing attachment to dna 1. Ligand diffuses through membrane 2. Ligand binds to ligand-binding domain on receptor a. receptor is in cytosol so translocation occurs and it will enter nucleus b. receptor is already in the nucleus and will be simply activated 3. Ligand-receptor complex will bind to its designated, specific DNA sequences which is referred to as the RESPONSE ELEMENT (aka enhancers aka regulatory elements) 4. The LR complex has a transactivation domain which recruits other transcription factors (proteins involved in any step of the process of converting DNA to RNA) which will (in)/activate transcription 5. Transcription factors brought by the LR complex to the transactivation domain either increase or decrease the production of mRNA 6. Translation of mRNA into functional proteins OR transcription factors which effect cellular processes and other gene regulation

Ligand-binding sites and the different things that bind there with proper terminology... - Lig - ag -anta

Ligand-binding sites only bind to particular structures! - Ligand: The natural or typical chemical that the receptor is made to bind to and is made/intended for - Agonist: A molecule that mimics the ligand, and can bind to the receptor site causing the same conformational change and signal response! - Antagonist: A molecule that binds to the ligand-binding site and causes NO response... essentially blocks ligand binding and inhibits a response (an example of drug treatment)... May compete with ligand for the site Note which causes responses! (all but antagonist)

Cell communication terminology... - Ligand (what two properties explain the binding?) - Receptor A receptors Specificity/affinity in a receptor/ligand complex...

Ligand: Chemical messenger that interacts with the receptor... - Binding is dictated by specificity and reversibility - Specificity: ligand will bind to specific receptors - Reversibility: Ligands are not permanently bound! Receptor: Protein which detects an incoming signal, the binding site of the ligand - receptors changing shape is what explains the communication... the signal will travel via a biochemical pathway deeper into cell For receptor/ligand complex... - Receptor specificity: Degree to which it can bind various ligands! Does it bind one (highly specific) or can it bind many (not very specific) - Receptor affinity: The strength of a ligand/receptor interaction which determines how fast and likely a ligand is to bind to its receptor

Biological response of CORTICOIDS... -Long term stress response and the adrenal cortex RESISTANCE PHASE (prior to exhausting all rserves) specifically glucocoritcoids! - whats involved and their properties - overall effect on body - mechanism - routes of action - Glucose sparing effect

Long term stress/Adrenal Cortex: - Releases Glucocorticoids (stress) and mineralocorticoids (electrolyte balance) - Glucocorticoids regulate metabolism through cortisol - Mineralocorticoids regulate electrolyte balance and are regulated by blood osmolarity - Long term stress results in loss of fat and muscle - When fat reserves are lowered, muscles are used via gluconeogenesis Refresher on the mechanism: - Stress -> brain -> CRH (hypothalamus) -> POMC cleavage into MSH and ACTH (anterior pituitary) -> stimulates adrenal cortex to release corticoids Physiological changes in long term stress... 1. Increased glucagon levels secreted by alpha cells to increase circulation glucose levels 2. Glucocorticoids works synergistically with Growth hormone!!!!!: results in the *The glucose sparing effect*: growth hormone causes lipolysis or fat breakdown into glucose and glucocorticoids also cause breakdown of glycogen (also lipids and sometimes protein) into glucose to provide energy to cells...!

Next peripheral endocrine gland: - Thyroid gland: hormones (whats special) - Negative feedback loops!

Means "Shield" in greek, in the neck on both sides of the larynx. Under normal conditions you should not be able to see or feel it. Responsible for T3/T4 hormones! T3 and T4 hormones are the ONLY hormones/molecules in the body that require and are derived from *iodine* Act through nuclear receptors to regulate gene transcription Hypothalamus produces TRH -> anterior pituitary produces TSH -> Thyroid gland makes T3/T4 hormones AND also *TSH causes thyroid gland to make more thyroid cells via mitosis* two feedback loops: 1. Normal hormone negative feedback.. T3/T4 hormones inhibit pituitary and hypothalamus 2. Increased levels of TSH also inhibits the hypothalamus from producing TRH.

Hormone receptors 2/3: Ligand-binding receptor (receptor-enzyme and GPCR)

Membrane binding receptor: Both transmembrane domain receptors (receptor enzyme and GPCR) signal transduction cascades which have effectors that go on to activate more and more components... A -> B + B -> C +C + C +C +C +C Three regions: - Extracellular domain: Ligand binding domain which interacts with chemical messenger - Transmembrane domain: Hydrophobic portion embedded in plasma membrane which transmits conformational change to the cytoplasmic domain - Cytoplasmic domain: Intracellular region which transduces signal to effector molecules

Hypothyroidism Thyroid Disorders... - Goiter - Cretinism - MYXEDOMA

Myxedoma: Abnormal accumulation of water and protein throughout body and disturbances in general metabolism - protein and fluid accumulation alter facial features. -Hypothyroidism later in life so there is inadequate metabolism--> individual may be cold all the time and have low energy (not fully metabolizing food/energy), change in skin texture and hair loss.

Negative feedback loop grand scheme

Now, not only does the ACTH inhibit hypothalamus, the hormone corticosteroids also inhibit ACTH (anterior pituitary) and hypothalamus (CRH)

Effects of hormones (chemical messengers) are diverse... - one can trigger... one phys process can be regulated by - All the diff functions of hormones...

One hormone can trigger multiple physiological responses and one physiological process can be regulated by many hormones. Hormones can have antagonistic effects (one produces an opposite effect of the other) - Regulate other glands - Regulate reproduction - Regulate metabolism - Regulate homeostasis - Regulate response to long term and short term stress - Regulate development, growth, and

Class messenger type: Protein/peptides - hydrophil or phob? - examples pathway

Overall: - chains of amino acids (2-200) - synthesized from mRNA - HYDROPHILLIC molecules - Therefore soluble in aqueous solutions (extra/intracellular fluid) and cannot diffuse across plasma membrane and synthesized in ADVANCE - examples: Vasopressin, growth hormone Pathway: - mRNA is translated on the rough endoplasmic reticulum (first cleavage occurs here... preprohormones to prohormones) - Stored in vesicles as prohormones (cleaved again into hormones in secretory vesicles before exocytosis secretion)

Posterior Pituitary Hormones... - Oxytocin main purpose? who it effects and the study?

Oxytocin: Used in uterine cell wall contraction and mammary gland contraction (milk excretion) - brain receives signal from uterus, causes hypothalamus to communicate release to posterior pituitary, oxytocin travels via blood stream to signal smooth muscle cells to contract! - Positive feedback!!! Contractions = more distortions so each time more oxytocin is released until the baby is delivered. - It effects males and females! College study done before and after injection of oxytocin into blood stream... $1,000 now or $10,000 after graduation, after injection more people picked the $10,000... it acts to give us *wiser judgment*

Antagonistic effects... The antagonist to Calcitonin is...

Parathyroid glands produce PTH (parathyroid hormone) - Parathyroid gland has two pairs embedded in the posterior surfaces of the thyroid gland. - *Hypercalcemic* response (Increase Ca Blood levels) - PTH increases Blood Ca level, controls calcium metabolism - Exactly the same three mechanisms of Calcitonin but in reverse - 1. Decrease Ca excretion in Kidneys (Increase renal tubule absorption) - 2. Increase Ca release from bones (bone resorption) - 3. Increase Absorption from diet in gut Regulation pathway: 1. Ca levels drop below 10 mg / 100mL 2. Stimulates PTH in parathyroid glands 3. PTH is released and acts to increase Gut absorption (through active vitamin D?) and bone resorption while decreasing excretion into urine. 4. Ca levels rise

Which Ca regulating hormone is more important for staying alive? overall img regulation present

Parathyroid hormone PTH! Parathyroid hormone ensures there are sufficient Ca levels for the body to use. Think about all the physiology that relies on calcium!

Insulin pathway (specifically in skeletal muscle cells)

Pathway... 1. Increased blood glucose stimulus causes beta cells to produce and release inslin 2. Insulin will enter the blood stream and find target cells (such as skeletal muscles) 3. Skeletal muscles in response to insulin (or exercise!) have stored GLUT4 glucose facilitator channel proteins in cytoplasmic vesicles which fuse with the membrane 4. Now the channels allow entry of glucose/AA/fats etc into the skeletal muscle.

Another brain endocrine gland... (Last of the neuroendocrine glands) - Pineal gland - Jet leg effect - Seasonal dep.

Pineal gland: produces the HYDROPHILIC, amino acid derived hormone melatonin - Melatonin is derived from serotonin by pinealocytes in pineal gland - Light is what regulates production of the hormone! We see light which sends a response through optic nerve to the brain which (in)activates pineal gland (light inhibits production) - Communicates with the hypothalamus and DIRECTLY controls sleep clock! Is referred to as out biological clock of the body Experiment with time change/jet leg... - Make two graphs, each labeled Y axis with melatonin concentration and X with time... - For our regular time/day/night graph we see a nice bell curve here melatonin is highest around midnight - When we travel to lets say Singapore, we completely reverse out sleep clock since its 12 hours ahead there, the bell curve flips upside down... - It takes 1 week to reacclimatize!! --- This explains why we are so tired, groggy, less, happy/joyful, etc. with jet leg because melatonin has roles on the hypothalamus which effects all endocrine glands via pituitary hormones... melatonin will then calm us but also help regulate hunger, emotion, etc. Special case: - Seasonal Affective Disorder (SAD): During winter months there is naturally less light so we have higher melatonin levels which keeps us calm and more depressed... Also explains our want for carbs, since melatonin increases metabolism our body wants energy.

Begin all anterior pituitary hormones... - Prolactin.. found in who? Effects?

Prolactin: Stimulates milk synthesis (lactation) - 4,5 ducts... 3 lobules - Found in ALL vertebrates even those without mammary glands effects of prolactin... 1. Osmoregulation: helps control water/solute levels in fish 2. Reproduction: As long as mom is giving milk it inhibits reproduction pathway... no new baby can be born, an evolutionarily favorable trait. 3. Development: Plays a role similar to GH in amphibians 4. Metabolism: Effects metabolic activity 5. 6. *Behavioral effects*: Prolactin promotes maternal behavior in people to act more cautiously (ALL people, not just pregnant)

Receptor enzyme pathway for tyrosine kinase...

Receptor enzyme tyrosine kinase pathway... 1. Ligand binds 2 inactive monomer receptors 2. Receptors dimerize 3. Autophosphorylation occurs on tyrosine residues 4. The active tyrosine kinase receptor enzyme now will phosphorylate kinases which leads to different signal cascades.

Transmembrane receptors continued.... Three different types of receptor enzymes

Receptor enzymes are receptors which also are involved in catalytic activity (phosphorylation capacity) at the cytoplasmic domain...

Regulators of Insulin production! TWO

Regulators... 1. The digestive tract stretch receptors trigger brain that will communicate to pancrease to produce insulin (ANY FOOD, regardless of what it is) 2. Blood glucose levels directly regulate the pancreas

Lec endocr II... Continued properties of steroid hormones: properties and pathway - protein? Properties of the protein? - bind to what kind of receptor(s)? - Effect is fast or slow?

Steroid Hormones: derived from cholesterol These hormones are hydrophobic! which means... - synthesized on demand - Require carrier protein (specifically ALBUMIN) for long distance transport through aqueous circulatory system (travel through blood vessels) **Albumin has a hydrophobic site (binds to the steroid hormone) and a hydrophilic site (dissolves in aqueous solution (blood) and helps with transporting** - Since hydrophobic, they can either bind to an intracellular receptor or transmembrane receptor - Effects on target cell are slow! This is because the steroid hormone causes gene transcription which takes a long time to carry out pathway: 1. Steroid hormones are synthesized in the cell. 2. Steroid hormones diffuse through the membrane since hydrophobic and eventually enter into the blood stream 3. In the blood stream, some steroids remain free messengers and others become bound to the hydrophobic sites on albumin 4. Free messenger exit the blood stream and enter the target cell binding to the intracellular receptor (can be transmembrane receptor in some cases) 5. Decrease in free messenger concentration causes albumin to release its ligand which also enters target cell (example of positive feedback!)

Class 3 of messengers: Steroid messengers classes

Steroid chemical messengers: Derived from cholesterol classes: - Mineralocorticoids: Electrolyte balance hormones (kidney) ex. aldosterone - Glucocorticoids: Stress hormones ex. Cortisol, corticosterone, cortisone - reproductive hormones: Sex-specific characteristics ex. estrogen, testosterone, progesterone - ecdysteroids (INVERTebrates) ex. ecdysone (for molting in insects/arthropods)

Thyroid temperature control pathway...

Stimulus that we are cold... hypothalamus releases TRH, ant. pit. releases TSH... Thyroid releases T3/T4 which finds target cells in body and will increase metabolism to raise temperature... a new "normal" homeostatic levels of T3/T4 will be in place until cold goes away.

Begin all anterior pituitary hormones... - ACTH

Stress stimulus from brain travels to hypothalamus which releases Corticotropin Releasing hormone (CRH) and which stimulates release of Adrenocorticotropic hormone (ACTH) by anterior pituitary... - ACTH stimulates adrenal cortex to release glucocorticoids (steroid hormones) in response to stress Pathway: *CRH actually creates ACTH and MSH* 1. Brain response to stress triggers Hypothalamus to release CRH 2. CRH stimulates breakdown of POMC 3. POMC presence in the anterior pituitary leads to it being broken down into two hormones, ACTH and MSH 4... a. ACTH will stimulate adrenal gland (cortex) to release glucocorticoids (like cortisol) b. MSH acts in non-vertebrates to change skin pigmentation (make darker) to better hide from predators 5. a. Cortisol then effects organs but also inhibits CRH production! (Negative feedback cycle of hormones)

Conceptual ideas/reminders: - Receptors and ligands properties continued... Target cells both express different _______.... And have a ____ for different _______

Target cells express different receptors - This explains/helps determine if a response will occur to a ligand/stimulus depending on if the receptor is present - Ligands can bind to multiple different receptors... -Allows ligands to have unique effect on target cells Target cells may have a receptor for many different ligands Example of this: A hormone can cause vasoconstriction in one case and vasodilation in another. Basically, one receptor can be targeted by different ligands and one ligand can have many different receptors creating diverse signaling effects.

Hashimoto Hypothyroiditis

The antibodies produced by the immune system attack the thyroid gland, which causes inflammation and death of the thyroid cells. This results in an underactive thyroid gland.

Continued... Receptor 3: GPCR properties and PATHWAYS

The first few steps in GPCR signaling are the same for most receptors... 1. Ligand binds the ligand-binding site 2. Conformational changes transmitted across transmembrane domain activating the cytoplasmic domain/G-protein 3. G-protein exchanges GDP and binds GTP 4. Beta/Gamma complex dissociate from alpha subunit - *** beta/gamme complex can stimulate downstream effects by opening or closing (regulating) ion channels*** 5. The alpha unit (in some cases it can be the beta/gamma unit) will activate the amplifier enzyme This ends the point where all GPCR's pathway is the same... The different amplifier enzymes (which create the secondary messengers) determines the effect on the cell.

Ligand-binding interactions rate follows... - What increases reaction/response rate - what decreases? - How can you increase sensitivity? When does this equation become irrelevant? - when does maximal response occur?

The law of mass action: The greater mass of reactants is proportional to the rate of reaction... This means... L + R <-> LR ----> response L = free ligand, R = Receptor, LR= Ligand-receptor binding complex - Increase Ligand or Receptor concentration (therefore increasing mass) and more Ligand binds receptors which produces more response - Increasing number of receptors increases SENSITIVITY of target cell to messenger meaning a smaller concentration of ligand will be required to produce a equally as strong response... This equation becomes irrelevant at the point of saturation... This is when all ligands are bound to a receptor so increasing ligand concentration will cause no increased response. - Saturation = maximal response - Can only increase response by adding more receptors (which also would increase sensitivity at the same time) - Look at graphs image... at 100% bound receptors, the chemical messenger/ ligand [M] is peaked... Increasing the receptor concentration results in less ligand to bind more receptors (increased sensitivity)

Which biogenic amine can readily diffuse through the membrane? Dopamine Maletonin Epi/NE Thryoid Hormone All above

Thyroid hormone T3/T4 since it is hydrophobic! The rest (and almost all) are hydrophillic!

Begin all anterior pituitary hormones... - TSH

Thyrotropin Releasing hormone stimulates pituitary to release thyroid stimulating hormone which acts on thyroid gland to release thyroxin (T3/T4)

Which is faster regulation/signaling? Intracellular receptors or transmembrane receptors?

Transmembrane receptors! They use transduction cascades which occurs in the cytosol so its effects are more rapid... Intracellular receptors use transcription cascades which required transcription in the nucleus and takes longer.

The Hypothalamus and its hormones - two types (R/I) - Types of releasing - GHRH special because

Two types of hypothalamus hormones... 1. Hypothalamus Releasing hormones (RH) or Releasing factors (RF)-- which stimulate anterior pituitary to release hormones The following have the general path.. Hypothalamus hormone induces release of anterior pituitary hormone which will find its endocrine gland target which releases its own hormone! --hypothalamus hormone -> pituitary hormone -> periphery gland and hormone - Thyrotropin-releasing hormone (TRH) -> TSH -> thyroid produced T3/T4 - Corticotropin-releasing hormone (CRH) -> ACTM - > adrenal cortex produced glucocorticoids - Corticotropin-releasing hormone (CRH) -> MSH -> changed pigmentation in lizards and/or adrenal cortex produced glucocorticoids - Gonadotropin Releasing hormone (GnRH) ->LH/FSH-> testes/ovaries produce estrogen - Growth Hormone Releasing Hormone (GHRH) -> GH (growth hormone) which is *special* because it targets and promotes growth in ALL organs/glands not just one! 2. Hypothalamus inhibiting hormones (IH) or inhibiting factors (IF)-- which inhibit production of anterior pituitary hormones. - Growth hormone inhibiting hormone (GHIH) GHRH and GHIH are in battle so we do not grow too much or too little! Both produced from the hypothalamus and regulate the anterior pituitary gland.

Mechanisms for signal inactivation...

a. Ligand removed by distant tissues: Ligand will be taken up and transported to a distant tissue to be degraded via the blood stream b. Ligand taken up by adjacent cell: Ligand is endocytosed by neighboring cell c. Ligand directly degraded by Extracellular enzymes: Ex. is peptide hormones proteases (Proteolytic hormone and vasopressin) d. Ligand-receptor complex removed and degraded via endocytosis: The cell the receptor is on will engulf the receptor and ligand via endocytosis and degrade it inside. e. Receptor inactivation: Some protein could phosphorylate/regulate the receptor to inactivate it. f. Inactivating signal transduction pathway: Inactivate some intracellular protein in the signaling pathway!

Site with all the hormones, class, effect, and gland!

https://courses.lumenlearning.com/suny-ap2/chapter/hormones/ Chart with all the hormones and knowledge

Hydrophilic vs hydrophobic messengers

hydrophilic: typically faster signaling, regulate by contorlling how many vesicles are released - STORED in the cell inside of vesicles! - Secreted via exocytosis - Readily dissolves in extracellular fluid... once diffused in extracellular fluid (such as blood) it can travel to target cell - canNOT diffuse across membrane Hydrophobic: takes longer to signal, regulate the synthesis since once they are made they find target cells - Made on DEMAND - Can DIFFUSE across the plasma membrane - Requires a CARRIER protein for long distance transport since it cannot dissolve in extracellular fluid