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ENDOCRINE: Endocrine glands o Ductless o Act with nervous system to coordinate and integrate activity of body cells o Influence metabolic activities by means of hormones transported in blood o Responses occur more slowly but they last longer than CNS/PNS Depends on size: bigger ones last longer because take longer to break down Hormones: long-distance chemical signals that travel in blood or lymph o Amino acid-based hormones: amines, thyroxine, peptides, and proteins Interact with receptor right on cell membrane o Steroids: synthesized from cholesterol Gonadal and adrenocortical hormones o Circulate in the blood either free or bound Steroid and thyroid hormones are attached to plasma proteins (ex: albumin) All other circulate without carriers Concentration of a circulating hormone reflects how fast they are made, how fast they are released, how fast they are inactivated and removed from body o Water-soluble hormones: all amino acid-based except thyroid Act on receptors in the plasma membrane, usually coupled via G proteins to secondary messengers o Lipid-soluble hormones: steroid and thyroid hormones Act on receptors in the cell, which directly activate genes o Blood levels of hormones are controlled by negative feedback systems Humoral Stimuli o Some glands secrete their hormones in direct response to changing blood levels of certain critical ions and nutrients o Ex: Ca2+ in the blood o Falling blood Ca2+ levels parathyroid glands release parathyroid hormone (PTH)PTH increasesstimulates osteoclasts to degrade bone matrix and release Ca2+ in the bloodBALANCE o Rising blood Ca2+ levelsparafollicular cells of thyroid release calcitoninosteoblasts deposit calcium slatsblood Ca2+ levels fall Neural stimuli o Nerve fibers stimulate hormone release o Under stress, sympathetic nervous system stimulates adrenal medulla to release epinephrine and norepinephrine Hormonal stimuli o Many endocrine glands release their hormones in response to hormones produced by other endocrine glands o Hypothalamic hormones stimulate the release of most anterior pituitary hormones o Anterior pituitary hormones stimulate targets to secrete more hormones o Hypothalamic-pituitary feedback loop: hormones from final target organs inhibit the release of anterior pituitary hormones Pituitary Gland o Two lobes: posterior (pituicytes and nerve fibers), and anterior (glandular tissues) Posterior o Is just a storage organ, not a true producing hormone gland, receives hormones from hypothalamus o Neural connection to hypothalamus o Neural hormones include oxytocin and ADH (antidiuretic) o Transported to posterior, stored till neural stimulus o Portal vein carries releasing and inhibiting hormones made in hypothalamus to the anterior pituitary to regulate hormone secretion from the AP o 1. Hypothalamic neurons synthesize oxytocin and ADH; 2. They are transported along hypothalamic-hypopheseal tract to posterior pituitary; 3. Are stored in axon terminals in posterior pituitary; 4. Are released into blood when hypothalamic neurons fire Anterior o 1. Stimulated hypothalamic neurons secrete releasing and inhibiting hormones; 2. These hormones travel through the portal veins to the AP where they stimulate or inhibit release of hormones from AP; 3. Anterior pituitary hormones secreted into secondary capillary plexus o Secretes 6 hormones o All are proteins TSH (thyroid), ACTH (adrenal), FSH, and LH (testis/ovary) Regulate secretory action of other endocrine glands(above) Growth Hormone (GH) o Hypersecretion: in children results in gigantism, adults in acromegaly (makes cells in face grow) o Hyposecretion: in children results in pituitary dwarfism o Produced by somatotrophs o Stimulates most cells, especially bone and skeletal muscle o Promotes protein synthesis and encourages use of fats for fuel o Most effects are mediated indirectly by insulin-like growth factors (IGFs) o GH release regulated by: Growth hormone-releasing hormone (GHRH) Growth hormone-inhibiting hormone (GHIH) o Direct action of GH Stimulates liver, skeletal muscle, bone, and cartilage to produce IGFs Mobilizes fat, elevates blood glucose by decreasing glucose uptake and encouraging glycogen breakdown (glyconeolysis) in liver Gonadotropins o Follicle-stimulating hormone (FSH) Stimulates gamete (egg or sperm) production o Lutenizing hormone (LH) Promotes production of gonadal hormones o Secreted by gonadotrophs of AP o *Puberty first, hormones second o Triggered by gonadotrophin-releasing hormone (GnRH) made in hypothalamus during and after puberty o Suppressed by gonadal hormones (feedback) Prolactin o Secreted by lactotrophs o Stimulates milk production right before lactation o Primarily controlled by prolactin-inhibiting hormone (PIH, dopamine) o Suckling stimulates PRH release and promotes continued milk production o Rise and fall with estrogen levels Oxytocin o Stimulates uterine contractions during childbirth o Triggers milk ejection (letdown reflex) in women producing milk o Stretching of the uterus sends signals to hypothalamus, which produces oxytocin in response o Positive feedback mechanism Thyroid-stimulating hormone (thyrotropin)/(TSH) o Produced by thyrotrophs o Stimulates normal development and secretory activity of the thyroid o Stimulated by thyrotropin-releasing hormone (TRH), made in hypothalamus o Inhibited by rising blood levels of thyroid hormones that act on pituitary and hypothalamus (negative feedback) Thyroid Gland o Two lateral lobes o Composed of follicles that produce the glycoprotein thyroglobulin o Colloid (thyroglobulin + iodine) fills the lumen of the follicles o Parafollicular cells produce calcitonin o Very vascular Hypothalamus(TRH)Anterior pituitaryTSHThyroid glandthyroid hormones (can feeback and inhibit above)target cells Thyroid hormone (TH) o Major metabolic hormone o T4 (thyroxine): has two tyrosine molecules + 4 bound iodine atoms o T3 (triiodothyronine): has 2 tyrosine + 3 bound iodine atoms 1. Thryoglobulin synthesized and discharged into follicle lumen (synthesize in ribosomes of rough ER, transported to Golgi, packaged in vesicles to go to follicle lumen) 2. Iodide is actively transported in from the blood 3. Iodide oxidized to iodine 4. Iodine is attached to tyrosine in colloid, forming DIT/MIT 5. Iodinated tyrosines are linked together to form T3/T4 6. Thyroglobulin colloid is endocytosed and combined with a lysosome 7. Lysosomal enzymes cleave T4/T3 from thyroglobulin and hormones diffuse into bloodstream o T3 is ten times more active than T4 o They both bind to target receptors o Peripheral tissues convert T4 to T3 if needed o Increases metabolic rate and heat production/energy release o Plays a role in: maintenance of blood pressure, regulation of tissue growth, development of skeletal/nervous system, repro capabilities o Rising levels of TH provide negative feedback inhibition on release of TSH o Hypothalamic thyrotropin-releasing hormone (TRH) can overcome the negative feedback during pregnancy or exposure to cold o Hyposecretion in adults-myxedema, endemic goiter if lack of iodine o Hyposecretion in infants- cretinism (mentally retarded, short body) o Hypersecretion- Graves’ disease (makes antibodies directed at thyroid follicular cells, continuously stimulate TH release) Pancreas o Pancreatic islets contain endocrine cells Alpha cells produce glucagon Beta cells produce insulin Type 1 diabetes- destruction of the beta cells Glucagon o Major target is the liver where it promotes: Glycogenolysis: breakdown of glycogen to glucose Gluconeogenesis: synthesis of glucose from lactic acid and noncarbohydrates Release of glucose to the blood o Humoral stimulus (low blood glucose)Hormonal release of glucagon o Low blood glucose levelpancreas secretes glucagon, stimulates glycogen breakdown in liver to glucoseblood glucose rises to normal range Insulin o Activates insulin receptor o Cascade leads to increased glucose uptake and enzymatic activities that Catalyze the oxidation of glucose for ATP production Polymerize glucose to form glycogen Convert glucose to fat (particularly in adipose tissue) o High blood glucose levelpancreas secretes insulinstimulates glycogen formation in liver, and stimulates glucose uptake by cellsblood glucose lowers to normal range o Diabetes mellitus (DM)- due to hyposecretion/hypoactivity of insulin Three signs: polyuria (huge urine output), polydipsia (excessive thirst), polyphagia (excessive hunger/food consumption) o Hyperinsulinism: excessive insulin secretion, results in hypoglycemia, disorientation, unconsciousness Hormone Action on Target Cells o 1. Alter plasma membrane permeability or membrane potential by opening or closing ion channels o 2. Stimulate synthesis of proteins or regulatory molecules o 3. Activate or deactivate enzyme systems o 4. Induce secretory activities (prolactin-milk letdown) o 5. Stimulate mitosis (GH) Two Mechanisms: o 1. Water-soluble hormones cannot enter target cells, act on plasma membrane receptors, coupled by G proteins to intracellular second messengers that mediate target cell’s response o 2. Lipid-soluble: can get through plasma membrane, acts on intracellular receptors that directly activate genes Cyclic AMP 2nd Messenger System o 1. Hormone binds to receptor o 2. Receptor activates G protein o 3. G Protein activates adenylate cyclase o 4. Adenylate cyclase converts ATP to cAMP (2nd messenger) o 5.cAMP activates protein kinases, which triggers response of target cells Direct gene activation through lipid-soluble hormones o 1. Steroid hormone diffuses through the plasma membrane and binds an intracellular receptor o 2. Receptor-hormone complex enters the nucleus o 3. The receptor hormone complex binds a specific DNA region o 4. Binding initiates transcription of the gene to mRNA o 5. The mRNA directs protein synthesis