Ch 11. Endocrine System

• Endocrine Glands:

  • do not have ducts
  • secrete hormones directly into the blood stream
  • neurohormones are secreted by the hypothalamus
• Chemical Classification:

  • Amines: E, NE
  • Polypeptides: ADH
  • Glycoproteins: FSH
  • Steroids: Testosterone
• Steroids: from cholesterol

  • Sex steroids: androgens and estrogens
  • Corticosteroids: made by the adrenal cortex.
• Lipophilic: nonpolar, hydrophobic

  • steroid hormones, thyroid hormones, and melatonin
  • diffuse through membrane
  • receptors in the cytoplasm and nucleus
  • can be taken orally -> quickly absorbed
• Hydrophilic: polar, water soluble

  • peptides, glycoproteins, and catecholamines
  • cannot cross the plasma membrane
  • cannot be taken orally
• Pre-hormones: molecules released by the endocrine gland and modified by the target cell. Functional hormone.
• Pro-hormones: an inactive hormone that has to be cut and spliced together to be active.
• Steroid Mechanism of Action:

  1. Hormone binds to carrier protein. 
  2. Hormone detaches from the carrier 
  3. Enters the target cell through the membrane. 
  4. In the cytoplasm, binds to the receptor. 
  5. Hormone Receptor Complex translocated into the nucleus. 
  6. Receptor protein binds to one of the hormone response element’s half-sites. 
  7. Another hormone/receptor combo binds to 2nd half site.
  8. Dimerize= join together. Homodimer. 
  9. Turns on or off transcription.
• Sex Hormones bind to Sex Hormone Binding Globulin.

  Corticosteroids bind to Transcortin.
• Thyroid Hormones:

  • 9-cis-ritonic acid from Vitamin A
  • Calcitonin from Vitamin D
  • T3 & T4 from Tyrosine
• T4: Tetraiodothyronine. Aka. Thyroxine

  T3: Triiodothyronine
• Thyroid Hormone Mechanism of Action:

  1. Transported in the blood via a carrier protein, Thyroxin Binding Globulin (TBG). 
  2. Bond breaks 
  3. T4 diffuses through the membrane. 
  4. T4 is enzymatically converted into T3. 
  5. T3 is going to be translocated into the nucleus. Encounters the nuclear hormone receptor. Already bound to half site of hormone response element.
  6.  T3 binds to the receptor (TR Receptor). The other half site has an RXR receptor for 9-cis-retinoic acid. 
  7. Dimerization to form a heterodimer. 
  8. Turns transcription on/off.
• 3 Ways Thyroid Mechanism is different from Steroid:

  1. Heterodimer vs. Homodimer
  2. Pre-hormone is present in thyroid hormone MoA
  3. the nuclear hormone receptor is already in the nucleus of the thyroid MoA
• Hydrophilic Family:

  • polypeptides, glycoproteins, and catecholamines
  • receptors are found on the cell membrane
• Adenylate Cyclase/ cAMP System:

  1. Hormone binds to the receptor. 
  2. G-protein does its thing. 
  3. G-protein turns on Adenylate Cyclase. 
  4. Adenylate cyclase converts ATP to cAMP. 
  5. cAMP binds to the regulatory subunit 
  6. Protein kinase phosphorylates proteins like enzymes, ion channels, etc. 
  7. Turn off: 
  8. Protein Phosphatase opposes protein kinase. 
  9. cAMP destroyed by PDE. 
  10. G-proteins turn themselves off. 
• Monoamines like E and NE use the Adenylate Cyclase/ cAMP system.
• Alpha 2 receptors use the Phospholipase C/ Calcium system.
• Phospholipase C/ Calcium System:

  1. The hormone binds to the receptor
  2. G-protein does its thing
  3. Turns on phospholipase C 
  4. Takes membrane phospholipid -> inositol triphosphate (IP3) and diacylglycerol (DAG) 
  5. IP3 binds to Ca2+ channels on the ER
  6. Ca2+ channels open -> Ca2+ diffuses into the cytoplasm
  7. Ca2+  binds to calmodulin
  8. Ca2+/clmodulin complex turns on protein kinase.
• Tyrosine Kinase System:

  1. 2 molecules of growth factor bind to two ligand-binding domains. 
  2. Dimerize
  3. Autophosphorylation 
  4. Changes the conformation of proteins of catalytic domain -> enzymatic activity turns on
  5. Catalytic domains -> phosphorylating tyrosine residues of signal proteins 
  6. Signal proteins leave the receptor and activate a metabolic pathway
• Ligands in the Tyrosine Kinase system are usually growth factors for cell division.
• Pituitary Gland dangles from the floor of the diencephalon (hypothalamus).
• 2 lobs of Pituitary: Anterior & Posterior
• Embryonic Origin of Pituitary:

  • notochord produces growth factor
  • hypothalamus evaginates down to form posterior
  • stomodeum evaginates and forms the anterior
• High concentrations of AP hormones cause hypertrophy.

  Low concentrations of AP hormones cause atrophy.
• Growth Hormone (GH):

  • controls tissue and organ growth
• Thyroid Stimulating Hormone (TSH):

  • acts on thyroid to release thyroid hormones (T3, T4, calcitonin, RXR)
• Adrenocorticotropic (ACTH):

  • acts on the adrenal cortex to secrete corticosteroids
• Follicle Stimulating Hormone (FSH):

  • Females: stimulates the development if follicles of the ovaries. Produce the egg and estrogen.
  • Males: act on the testes and triggers them to produce sperm.
• Luteinizing Hormone (LH):

  • Females: triggers ovulation, releasing the egg from the ovary. Development of the corpus luteum.
  • Males: act on interstitial cells of the testes -> produce testosterone.
• Prolactin (PRL):

  • Females: stimulates milk production after childbirth
  • Males: a supporting role in males.
• Antidiuretic Hormone (ADH): causes the kidneys to conserve water.

  • urine volume decreases, urine color is bright yellow
  • inhibited by stretch receptors in the LA of the heart
  • Alcohol consumption increases the inhibition of ADH
• Oxytocin:

  • contractions of the uterus during childbirth
  • milk ejection response in lactating females
• Posterior pituitary secretes 2 hormones, that are produced in the Hypothalamus.
• Infundibulum connects the hypothalamus to the posterior pituitary.
• The hypothalamus acts on the anterior pituitary via hormones. Hypophyseal portal system.
• Growth Hormone Releasing Hormone (GHRH): stimulates secretion of GH
• Somatostatin: inhibits GH release.
• Thyrotropin Releasing Hormone (TRH): secretion of TSH. Also stimulates Prolactin production.
• Corticotropin-releasing hormone (CRH): stimulates the secretion of ACTH
• Gonadotropin-releasing hormone: secretion of FSH and LH.