NUSCTX 11 Final Exam 2025

How does the endocrine system work? - -Endocrine means "internal secretion" - it is a system of glands that secrete or release signaling molecules called hormones that affect the physiology of particular organs; the endocrine system regulates many different aspects of physiology (development, growth, metabolism, mood, behaviors, specific tissue function) The brain, especially the hypothalamus, produces regulatory hormones while the pituitary gland secretes hormones controlling specific hormones secreted by the endocrine glands What are hormones? - -Hormones are a class of substances that are produced by endocrine glands that are secreted into the blood (circulatory system), which is why they can travel far int he body and target specific organs They are potent chemicals (powerful and don't need a very high concentration of molecules to exert biological actions) - when measuring hormone levels in the body, they are in very low concentrations (picomolar or nanomolar) because they are so potent and need to be maintained in a narrow range (too much or too littel can cause different issues, leading to various diseases and disorders) Three Main Categories of Hormones - -Peptide hormones: chains of amino acids (building blocks for proteins); between 3-20 amino acids (longer chain that are protein hormones); have different charges (positive, negative, neutral); the longer the chain, start forming tertiary structures and fold together because of various charges; majority of hormones in the body are peptide hormones, chemically water soluble - example: insulin, glucagon Amine Hormones: in organic chemistry, an NH2 group attached to a carbon ring (derived from amino acids as well - single amino acid, mostly tyrosine); also water soluble since they come from amino acids, except for thyroid hormones (which structurally contain iodine, making them lipophilic) - example: catecholamines, thyroid hormones Steroid Hormones: lipophilic (made of lipids), derived from cholesterol (lot of carbon rings and a pentagon ring, methyl groups - do not see this in any of the hydrophilic groups) - examples: sex hormone, glucocorticoids Water-Soluble Signaling - -Receptors are embedded within the cell membrane - if it is secreted from the original gland, it travels in the blood, only recognizes cell type that has the receptor in the membrane; water-soluble hormones are unable to pass through cell-membranes (which is why receptors are embedded in the membrane, so that they can bind to the receptor without having to pass through); membrane-bound receptors NUSCTX 11 NUSCTX 11 have a polar signal exposed to external cell environment (water-soluble hormones travel in the blood, bind to polar part of receptor, and have internal signaling molecules to carry out hormone signals and effects inside the cell) Dissolve in water (hydrophilic) because they are formed from amino acids (cannot pass through target cell membrane) - examples include insulin, glucagon, catecholamines (dopamine, epinephrine, norepinephrine) Because it binds to the cell surface receptors, for signaling effects to take place, pathway requires second messengers to mediate the signaling (cAMP and cGMP - other proteins help amplify the signaling from the hormone and carry it out inside of the cell) Epinephrine Hormone Signaling - -Epinephrine is secreted from the adrenal gland, biological function is to mediate fight-or-flight response; initial secretion is from the adrenal gland into blood system, travel in circulatory system to identified targets; epinephrine acts on the cell because it is a target cel (express its own specific receptor) Binds to its receptor (without binding, receptor is inactivated with G protein bound to GDP molecule, gamma and beta subunits inhibitory; when bound, it becomes activated - GDP exchanged from GTP, beta and gamma unit come off); once bound to GTP, highly active and can bind to next part of signaling pathway (enzyme adenylate cyclase, which converts ATP to cAMP, a second messenger) cAMP can cause a robust response and mediate a lot of the downstream actions (ex: activate protein kinase A) Insulin and Glucagon - -Insulin: maintain glucose homeostasis by regulating plasma blood glucose levels (regulates carbohydrates, fat, and proteins, has an anabolic action [absorbs or stores energy], works to maintain and lower blood glucose levels by uptaking glucose from blood circulation and depositing into fat and muscle tissue) - secreted when blood glucose levels are too high (usually after eating a meal) Glucagon: work to maintain glucose homeostasis by regulating plasma blood glucose levels; catabolic (breaks down and is secreted from the pancreas); goal is to generate more plasma blood glucose (glycogenolysis [breakdown of different tissue glycogen and glucose stores, release into blood, increase blood plasma glucose levels when low] and gluconeogenesis [produce glucose from breaking down different tissues like adipose and muscle]) Insulin works to lower blood glucose levels (if blood glucose levels are low, do not want to increase insulin); glucagon works to increase blood glucose levels (glucagon is higher when blood glucose levels are low) When blood glucose is low, there is no reason to have insulin; as eat, levels start to climb (body will work to try and lower blood glucose levels, insulin spikes); when blood NUSCTX 11 NUSCTX 11 glucose levels are higher because of eating, no reason to continue raising levels (glucagon tapers down after meals) Fat-Soluble Hormone Signaling - -Lipophilic, can pass through lipid bilayer without tissue, receptors inside cell in cytosol - once hormones bind to the receptor, the function of nuclear receptors are that they can add a transcription factor (bound, enter nucleus, mediate actions of causing and affecting gene expression) Dissolve in fat rather than water because they are made from cholesterol and can pass through the cell membrane (can enter cell, receptors located intracellularly) - examples include glucocorticoids, thyroid hormones, estrogen, aldosterone, and testosterone Example: Glucocorticoid receptor is intracellular and works as a transcription factor (bind to promoters of target genes, help induce transcription of a gene); don't always want transcription factors to be active (gene expression and protein synthesis need to be controlled) - nuclear receptors are inactive in cytosol when there is no hormone bound to it (HSP complex is a chaperone protein complex that holds receptor inactive when there is no steroid hormone, comes off when steroid hormone binds, allows receptor to enter nucleus) How to regulate hormone secretion? - -Insulin and Glucagon are counter-regulatory (one promotes and other suppresses glucose levels) - not all hormones int he body have a pair Negative Feedback Inhibition System: starts with hypothalamus (secretes particular "releasing" hormones to anterior pituitary), anterior pituitary secretes "stimulating" hormones that travel in the blood to target peripheral endocrine glands (which secrete hormones to carry out physiological actions) Example: HPT Axis - hypothalamus secretes TRH, which signals to the anterior pituitary to secrete TSH (Thyroid-Stimulating Hormone); TSH enters the blood stream, travels to thyroid gland, and tells the thyroid gland to create thyroid hormones T3 and T4; when there is enough T3 and T4, negative signal feeds into upper layers of axis to suppress the anterior pituitary and hypothalamus (less TRH and less TSH leads to the production of less hormones); negative feedback decreased, increase in TRH and TSH allowing for more production of thyroid hormones How Do Endocrine Disruptors Work? - -Endocrine Disruptors: exogenous ("outside" chemicals that disrupt the endocrine system by mimicking or blocking hormone actions Alter Hormone Levels - hormones need to be well-regulated (potent in small amounts, regulated in counter-regulatory or negative feedback loop systems); disruptors can interfere with regulatory systems Bind to Receptors (Agonism) or Block Hormonal Action (Antagonism) - hormones are first messengers; endocrine disruptors can bind to receptors and mimic hormone action (agonism) or the endocrine disruptor can bind to hormone and block endogenous NUSCTX 11 NUSCTX 11 hormone binding (antagonism) - limited number of receptors (if body is overwhelmed with endocrine disruptors, normal endogenous hormones are unable to bind) Hormones Need to Mediate Signaling - endocrine disruptors an alter hormonal responses and steps in actions that occur downstream after binding to receptor (disrupt hormone signaling) Can cross the placenta barrier and potentially affect fetus (effects can linger longer after the child is born) - trans-generational effect Toxicants vs. Endocrine Disruptors - -Toxicants: response in a linear dose, response curve (dose is important factor - able to predict response because it follows a pattern) Endocrine Disruptor: dose-response curves are non-monotonic (not a linear curve), depending on type of chemical can respond in varied ways that are difficult to predict; no clear threshold Mechanism of Action for DDT - -Synthetic chemical, used as an insecticide (World War II - combat malaria typhus, effective against malaria and other insect-borne human diseases); brought into wide agricultural and commercial use (80 million pounds applied all over the world from the 1940s to 1960s); in the 1970s, people began to have increased awareness of detrimental effects (usage declined due to insect resistance and environmental and health concerns); 1972, DDT banned in the US because of harmful environmental impact and potential hazard to human health Silent Spring (Rachel Carson): increased mortality in birds due to application of the toxin; DDT implicated in bio-concentration and biomagnification in food chains; raised political awareness; accused chemical industry of spreading disinformation and public officials of accepting industry claims uncritically Endocrine Disruptor: reproductive abnormality (body breaks it down, metabolizes compound into DDE, another endocrine disruptor); long half-lives because they can accumulate in fat tissue, slowly released in body (long-lingering effects); DDE is androgen receptor antagonist (blocks effect); rats tested with DDT have decreased sperm number and motility, decreased testosterone production, and increased FSH and LH (hormones found in biological females); DDT mimics estrogen; exposure to DDT leads to birds having thinner egg shells (higher probability birds will not survive, reduction in enzyme key to shell formation)