endocrine

• Endocrine System


  The system of glands that secrete hormones directly into the bloodstream to regulate the body's metabolism, growth, sexual function, and other processes

  
• Endocrine Tissues


  • Diverse and decentralized
  • Release releasing and inhibitory hormones (hypothalamus), systemic hormones (pituitary)

  
• Endocrine Cell


  Releases chemical messengers (hormones) into the bloodstream
• Hormones


  • Regulate physiological processes
  • Variety in chemical structure
  • Released in very low quantities
  • Movement through diffusion or plasma
  • Bind to receptors on target cells
  • Released in response to changes in homeostasis

  
• Lipophilic Hormones


  Lipid; can penetrate membranes, receptor in cell
• Hydrophilic Hormones


  Water loving; receptor in membrane
• Autocrine Hormones


  Act on the same cell
• Paracrine Hormones


  Act on neighboring cells
• Negative Feedback Loop


  Mechanism of hormone regulation
• Positive Feedback Loop


  Mechanism of hormone regulation, but not as common

  
• Upregulation


  Increasing receptor levels on target cells
• Downregulation


  Decreasing receptor levels on target cells

  
• Permissiveness


  The process of hormones regulating the receptor levels of other hormones

  
• In rare cases, a hormone can regulate levels of its own receptor

  
• Neurotransmitters


  Release is "all or nothing", vary in frequency
• Hormones


  Levels never approach zero, fluctuate between high and low
• Types of Hormones


  • Peptide - most common
  • Steroids - lipophilic
  • Amino Acid Derived

  
• Peptide and Protein Hormones


  Synthesized in an inactive form, encoded by genes, multiple peptide hormones can be encoded by one gene, signal peptide directs hormone to correct intracellular organelle for processing

  
• Other Peptide Hormones


  • Pro-opiomelanocortin (POMC)
  • ACTH - release corticol
  • Lipotropin - promotes release of fat reserves
  • Endorphin - cause analgesic effect
  • MSH - associated with skin pigmentation, sleep activity and appetite

  
• Prohormone Processing


  • Proinsulin
  • Insulin
  • C-peptide (marker)

  
• Amino Acid Derivative Hormones


  Biochemically synthesized from amino acids, stored within vesicles, e.g. epinephrine (catecholamine)

  
• Processes That Influence Hormone Secretion


  • Changes in a critical physiological factor (e.g., ions)
  • Direct input from the nervous system through neurohormone release
  • Actions of other hormones (e.g., hypothalamic regulation of pituitary gland)
  • Mechanical stresses or cellular metabolism

  
• Things to consider about each hormone: process of hormone secretion, the chemical type, gland or cell, transport, target cell, response and regulation
• Water-Soluble, Free Hormones


  Smaller than kidney filtration barrier, excreted in urine

  
• Lipid-Soluble Hormones


  Some excreted in urine (if chemically modified to be more water-soluble), otherwise excreted in GI tract

  
• Half Life


  Time required to reduce blood concentration of a hormone by 50%
• Metabolism can change hormone levels or activity, e.g. sulfation or glucuronidation
• 1. Protein Coupled Receptors (GPCRs)


  • Integral membrane proteins, extracellular region binds hormone, intracellular region interacts with G-proteins
• Gαs


  Activates adenylate cyclase (AC), converts ATP to cAMP
• Gαi


  Inhibits adenylate cyclase (AC), blocks production of cAMP
• Gαq


  Activates phospholipase C (PLC), breaks down PIP2 into IP3 and DAG
• Effects of cAMP


  Activates Protein Kinase A (PKA), degraded by phosphodiesterase (PDE)
• Effects of DAG and IP3


  IP3 causes Ca2+ release from ER, DAG activates Protein Kinase C (PKC)
• One-Transmembrane Spanning Receptors (1-TMS)


  • Integral membrane proteins, extracellular region binds hormone, intracellular region contains a kinase domain; directly activates enzymes without G-proteins
• Nuclear Receptors


  • Found inside the cell, act as transcription factors, generally cytoplasmic proteins complexed with heat shock proteins (HSPs), hormone binding leads to dissociation of HSPs, dimerization to a second bound receptor, and translocation to the nucleus
• Diseases Caused by Mutations in Hormone Receptors


  • Thyroid stimulating hormone receptor - Grave's disease (hyperthyroidism)
  • Parathyroid hormone receptor - Jansen's metaphyseal chondrodysplasia
  • Follicle-stimulating hormone receptor - Ovarian dysgenesis type I
  • Melanocortin/adrenocorticotropic hormone receptor - Familial glucocorticoid deficiency
  • Luteinizing hormone receptor - Familial male precocious puberty
  • Antidiuretic hormone receptor - Familial hypocalciuric hypercalcemia
  • Gonadotropin-releasing hormone receptor - Hypogonadotropic hypogonadism
• The hypothalamus is located inferior to the thalamus and is part of the limbic system
• The hypothalamus contains many distinct nuclei that produce and release unique hormones
• The hypothalamus is sexually dimorphic (different between men and women)
• The hypophyseal portal system connects the hypothalamus and anterior pituitary via two capillary beds in series