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  • The Human Endocrine System

  • ENDOCRINE SYSTEMEndocrine glands: glands that lack ducts (ductless), secrete hormones directly into the blood that affect target cells.

    Exocrine glands are the ones that their secretions go via ducts to the lumen of other organs (like salivary glands leading to oral cavity ) or outside the body (sweat glands).

    Hormones are biologically active molecules, that affect metabolism of their target organs, help regulate total body metabolism, growth, reprodution.

    Neurohormones are secreted into blood by specialized neurons.

  • Why hormones affect only the target organ?Hormones are regulatory chemicals that work at a distance between organs traveling through the bloodstream from the gland to the target cell. The hormone binds only to cells having its receptor. Signaling can also be paracrine or autocrine.

  • Neural and Endocrine RegulationBoth use chemicals to communicate Some are used both as hormone and neurotransmitters (NTs).Differences:NTs diffuse across a synaptic cleftHormones are transported in blood. They have more diverse effects on their targets.Physiological regulation:Targets for both NTs and hormones must have specific receptor proteinsBinding must cause a specific sequence of changes in the target cellsMust be a mechanism to turn off the action of the regulator. The endocrine system rely on negative feedback mechanisms.

  • Hormones classes based on their chemistryAmines: are hormones derived from 2 amino acids (tryptophan and tyrosine) they include hormones secreted from: 1- Thyroid gland : T3 and T4. 2- Pineal gland : melatonine. 3- Adrenal medulla: epinephrine and norepinephrine.

    polypeptides: less than 100 aminoacids e.g ADH Proteins: more than 100 aminoacids e.g Growth hormones.

    Glycoproteins: consist of polypeptides with one or more carbohydrate groups e.g: follicle stimulating hormone (FSH), Luteinizing hormone (LH) and thyroid stimulating hormone (TST).

    Steroids are lipids derived from cholesterol e.g progesterone, testesterone, estradiol, cortisol, aldosterone.

  • Lipid-soluble (hydrophobic)Water-soluble (hydrophilic)PolypeptidesSteroids0.8 nmInsulinCortisolAminesEpinephrineThyroxine

  • Polarity of the hormonesPolar hormones water-soluble.Polypeptides, glycoproteins hormonesException: melatonin derived from nonpolar amino acid tryptophan can pass through the plasma membrane

    Nonpolar or lipophilic hormones insoluble in water and can pass through plasma membrane of their target cells Steroid hormonesThyroid hormones: composed of the amino acid tyrosine with iodine atoms

    Steroid and thyroid hormones are active when taken orally e.g contraceptive pills. Melatonine is also taken orally.

    Polypeptide and protein hormones are not given orally e.g insulin injections.

  • Prohormones and PrehormonesProhormones precursors moleculese.g. proinsulin is cut and spliced together to form insulin

    Prehormones precursors of hormonese.g. preinsulin

    Some hormones are inactive until activated by target cellsThe term prehormone designates the molecules secreted by endocrine glands but are inactive until they are changed into active form in their target celle.g. thyroxine (T4) is inactive until converted to T3 in target cellsPrehormone = T4 (inactive) T3 (active)Prehormone = Vit D3 (2 hydroxylations) 1,25 dihydroxyvit D3 (active).

  • Hormone InteractionsTarget tissue usually responds to a number of different hormones

    1. Synergistic two hormones work together Produce a larger effect together than the added effecte.g. norepinephrine and epinephrine on heart rate

    -FSH and testesterone each is important in specific step in spermatogenesis; complimentary action.

    -Estrogen, cortisol, prolactin, have complimentary effect on mammary glands to produce and secret milk.

  • 2. Permissive effect one hormone enhances theresponsiveness of a target organ to a second hormonee.g. estradiol induces formation of receptors for progesterone.Low calcium levels in blood stimulates the release of parathyroid hormone (PTH) which has Permissive effect on Vit. D. PTH induces Vit D hydroxylations in liver and kidney 1,25 dihydroxy vit D increases Ca2+ reabsorbtion by intestine thereby rises Ca2+ level in the blood.

    3. Antagonistic action of one inhibits the effect of the othere.g. lactation during pregnancy (high prolactin) inhibited by estrogen (inhibits secretion and action of prolactin). pancreatic islets secrete Insulin and Glucagon which has Antagonistic effects.Hormone Interactions

  • Body cells take up more glucose.InsulinBeta cells of pancreas release insulin into the blood.Liver takes up glucose and stores it as glycogen.Blood glucose level declines.Blood glucose level rises.Homeostasis: Blood glucose level (70110 mg/m100mL)STIMULUS: Blood glucose level rises (for instance, after eating a carbohydrate-rich meal).Liver breaks down glycogen and releases glucose into the blood.Alpha cells of pancreas release glucagon into the blood.GlucagonSTIMULUS: Blood glucose level falls (for instance, after skipping a meal).

  • Hormone Levels and Tissue ResponsesHalf-life time required for plasma concentration of a hormone to be reduced by halfRanges from minutes to hours for most (days for thyroid hormones)

    Normal tissue responses produced only when hormones are within normal physiological range

    High (pharmacological) doses cause side effectsProbably by binding to receptors of different but closely related hormones

  • Hormone Levels and Tissue Responses Priming effect (upregulation)a hormone induces more of its own receptors in target cellsResults in greater response in target celle.g. GnRH secreted by the hypothalamus increases sensitivity of anterior pituitary cells to further stimulation (upregulation of receptors)

    Desensitization (downregulation) occurs after long exposure to high levels of polypeptide hormone (e.g. adipose cells to insulin)Subsequent exposure to this hormone produces a lesser response (downregulation of receptors)Most peptide hormones have pulsatile secretion (spurts) which prevents downregulation

  • Mechanisms of Hormone ActionTarget cell receptors showspecificity, high affinity (strength of binding), and low capacity (saturation) for a hormoneLipophilic hormones have receptors in target's cytoplasm and/or nucleus diffuse through plasma membrane target is the nucleus where they affect transcriptionCalled genomic action and takes at least 30 minutes

    Receptors for hydrophilic hormones are on surface of target cellThese act through 2nd messengers; effects are quickSome steroids also act on cell surface receptorsCalled nongenomic action

  • Mechanism of Steroid Hormones Lipid hormones travel in blood attached to carrier proteinsdissociate from carrierspass through plasma membrane to target cell

    Bind to receptors in the cytoplasm nuclear hormone receptor

    Hormone-receptor complex translocates to nucleus binds DNA

    Genetic transcription and translation produce proteins

  • Nuclear Hormone ReceptorsServe as transcription factors when bound to hormone ligands to activate transcription

    Superfamily" steroid family and thyroid hormone family Also Vitamin D and retinoic acid

  • Hormones That Use Second MessengersWater soluble hormones use cell surface receptors

    Actions are mediated by 2nd messengers Hormone is the extracellular signal2nd messenger carries signal from receptor to inside of cell

    Adenylate Cyclase-cAMP 2nd Messenger System cAMP mediates effects of many polypeptide and glycoprotein hormonesHormone binds to receptor causing dissociation of a G-protein subunit that binds to and activates adenylate cyclaseInhibitory subunit dissociates, activating protein kinasePhosphorylates enzymes that produce hormones effectscAMP gets inactivated by phosphodiesteras

  • Adenylate Cyclase-cAMPBinding converts ATP into cAMP attaches to inhibitory subunit of protein kinase

  • Table 11.4

  • Phospholipase-C-Ca2+ 2nd Messenger SystemServes as 2nd messenger system for some hormonesHormone binds to surface receptor activates G-protein activates phospholipase C

  • Phospholipase-C-Ca2+Phospholipase C splits a membrane phospholipid into 2nd messengers IP3 and DAGIP3 diffuses through cytoplasm to ER causing Ca2+ channels to openCa2+ diffuses into cytoplasm and binds to and activates calmodulinCa2+-Calmodulin activates protein kinases phosphorylate enzymes that produce hormone's effects

  • Endocrine GlandsMany endocrine glands are organs whose primary function is hormone secretion.

    Some are mixed glands: e.g the pancreas is an endocrine and exocrine gland.

    Steroids are secreted by only the adrenal cortex and the gonads (testis & ovary).

  • Pituitary GlandLocated beneath hypothalamus at base of forebrainAlso called hypophysis

  • Pituitary GlandStructurally & functionally divided into anterior and posterior lobes

    Hangs below hypothalamus by infundibulum

    Anterior produces own hormonesControlled by hypothalamus

    Posterior stores and releases hormones made in hypothalamus

  • Posterior Pituitary GlandStores and releases vasopressin also called antidiuretic hormone (AVP or ADH) and oxytocin Hormones are made in the hypothalamus

    Supraoptic nuclei of hypothalamus produce ADH

    Paraventricular nuclei produce oxytocin

    Both are transported along hypothalamo-hypophyseal tract to posterior pituitary

  • Hypothalamic Control of Posterior Pituitary

    Neurons in the hypothalamus called neurosecretory cells produce Antidiuretic hormone (ADH) that promotes reabsorption of water from the

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