1. Endocrine systems
    1. Properties of hormones
      1. Synthesized by specific tissues or glands
      2. Secreted into the bloodstream (travels here to the site of action)
      3. Changes activities of target tissues or organs
      4. Actions are caused by the hormone binding to receptors
    2. Chemical types and general functions
      1. Amines - small molecules derived from amino acids (eg Epinephrine and norepinephrine from tyrosine)
      2. Prostaglandins - cyclic unsaturated hydroxy fatty acids
        1. Perform a variety of functions: induce labor, treat asthma, reduce stomach acidity
      3. Steroid hormones - synthesized from cholesterol (testosterone, estrogen)
      4. Peptide and protein hormones - largest and most complex group (insulin)
      5. Hormone's effects last from minutes to days
    3. Regulation of secretion
      1. Neurohormones - nervous system innervates endocrine tissues, affects hormone secretion
      2. Feed-forward - secretion is not affected by the hormone or its effects
      3. Feed-back - can be negative or positive - secretion is affected by the hormone or its affects
  2. Neuroendocrine systems
    1. Neurosecretory cells (specializations)
      1. Larger diameter of vessicles (secretory: 100-400 nm, synaptic: 30-60 nm)
      2. Use fast axonal transport only
      3. Form a neurohemal organ (where the nerve ending terminates on a bed of capillaries)
    2. Hypothalamic control of anterior pituitary gland
      1. Uses releasing and release inhibiting hormones (table 9-2)
      2. Hormones are released at the median eminence into the portal vessels to the anterior pituitary
      3. Very low concentrations are needed because of the direct route between the two
      4. CRH (corticotropin releasing hormone) causes the release of ACTH (adrenocorticotropic hormone)
    3. Hormones released from the Anterior Pituitary (Adenohypophysis)
      1. Growth hormone (GH) / Somatotropin
      2. Prolactin (PRL)
      3. Adrenocorticotropic hormone (ACTH)
      4. Thyroid stimulating hormone (TSH)
      5. Luteinizing hormone (LH)
      6. Follicle Stimulating Hormone (FSH)
    4. Hormone released from the intermediate lobe of the Pituitary (pars intermedia)
      1. Melanocyte stimulating hormone (MSH)
    5. Hormone released from the posterior pituitary (neurohypophysis)
      1. Antidiuretic hormone (ADH) / vasopressin
      2. Oxytocin
      3. Synthesized in the hypothalamus, travel down axons in the hypothalamo-hypophyseal tract to the posterior pituitary where they are released
      4. Hormones are cleaved to their active form when they are released into the blood
  3. Cellular mechanisms of hormonal action (9-8)
    1. Lipid-soluble hormones (and cytoplasmic receptors) (9-9)
      1. Transport via blood
        1. Bound to carrier proteins
        2. Increases plasma concentration of hormones (steroid and thyroid)
      2. Dissociation and diffusion across the membranes
      3. Formation of hormone - receptor complexes (removes inhibitor)
      4. Complexes move into nucleus
      5. Complexes bind to DNA, alter the transcription rates
      6. Effects are slow but last hours to days
    2. Lipid-insoluble hormones (and intracellular signaling) (9-11)
      1. Types of second-messenger signaling
        1. Cyclic nucleotide phosphates (cNMP's)
        2. Inositol phospholipids (IP3 and DAG)
        3. Ca2+ ions
      2. Steps in second-messenger signaling systems
        1. Ligand (hormone) binds to a receptor linked to a transducer protein
        2. Transducer protein (G-protein) activates an amplifier (enzyme)
        3. Amplifier (enzyme) creates the active second messenger
        4. Second messenger binds to an internal regulator
        5. Regulators cause effectors to perform an action which leads to a cell response (step 5 can be repeated several times before the final cell response)
      3. You are responsible for knowing how each of the general steps relates to specific pathways (figs 9-12, 9-15, 9-19; pgs 314-327)
      4. Diversity of Responses to a single second-messenger is determined by
        1. Types of receptors
        2. Compartmentalization of receptors, amplifiers, effectors, etc.
        3. Different isoforms of an effector (eg - different isoforms of PKA)
        4. Helper proteins (which may help the amplifier link to the substrate, etc.)
    3. Prostaglandins - exception to the rule
      1. Lipid soluble, but bind to cell surface receptors
      2. Use second-messenger signaling
  4. Physiological Effects of Hormones
    1. Metabolic and Developmental Hormones
      1. Adrenal Gland
        1. Medulla (see chapter 8)
          1. Epinephrine
          2. Norepinephrine
        2. Cortex
          1. Stimulated by ACTH (adrenocorticotropic hormone)
          2. Synthesizes three groups of hormones
            1. Reproductive hormones
            2. Mineralocorticoids (kidney function)
            3. Glucocorticoids (cortisol, cortisone, corticosterone)
              1. Negative feedback on CRH in hypothalamus
              2. Stress increases ACTH® ­ glucocorticoids
              3. ­ gluconeogenesis in liver
              4. ­ use of fat stores
              5. ¯ muscle uptake of glucose and amino acids (useful in starvation conditions)
      2. Thyroid hormones (lipid-soluble)
        1. Stimulated by TSH (thyroid stimulating hormone)
        2. Two types: 3,5,3'-triiodothyronine and thyroxine
          1. Requires iodine for synthesis
        3. Negative feedback to TRH (TSH releasing hormone)
        4. Sensitizes liver, kidney, heart, nervous system, and skeletal muscle to epinephrine
        5. Increases metabolic rate
        6. Works with growth hormone in development to ­ protein synthesis
          1. ¯ iodine at these times causes a condition known as cretinism
          2. ¯ iodine causes goiter (because of an increase in TSH which stimulates growth of the thyroid gland)
      3. Insulin and glucagon
        1. Insulin
          1. Secreted by b -cells in islets of Langerhans
          2. Release is stimulated by ­ in plasma glucose, glucagon, growth hormone, gastric inhibitory peptide (GIP), epinephrine, or ­ levels of amino acids
          3. ­ glucose uptake into cells
          4. ­ glycogenesis (­ glycogen stores)
          5. ­ lipogenesis (­ fat stores)
          6. ­ uptake of amino acids, and synthesis into protein
          7. Diabetes (disease state)
            1. Type I - decrease in b -cell mass
            2. Type II - defective insulin receptors
            3. Causes hyperglycemia, glycosuria, and increased levels of ketone bodies
        2. Glucagon
          1. Secreted by a -cells of the pancreas
          2. Stimulated by ¯ plasma glucose
          3. ­ glycogenolysis, lipolysis, and gluconeogenesis
      4. Growth Hormone (GH)
        1. Regulated by growth hormone releasing hormone (GRH) and growth hormone inhibiting hormone (GIH/somatostatin)
          1. GIH and GRH are regulated by blood glucose levels
        2. ­ stored fat and fatty acid uptake in muscle (conserves the glycogen stores in muscle)
        3. ­ plasma glucose levels
          1. ­ gluconeogenesis and fatty acid utilization
          2. ¯ glucose uptake (except for the nervous system) and therefore glucose utilization
        4. stimulates insulin secretion (directly and via feedback)
        5. stimulates RNA and protein synthesis
        6. stimulates production of insulin-like growth factors
        7. abnormalities/disease states
          1. gigantism - ­ GH before puberty
          2. acromegaly - ­ GH after puberty
          3. dwarfism - ¯ GH during childhood and adolesence
    2. Water and Electrolyte balance
      1. Antidiuretic hormone (ADH/ Vasopressin)
        1. Stimulated by high blood osmolality
        2. Increases water absorption in the kidney
        3. Has positive effects on release of ACTH and TSH
      2. Mineralocorticoids (eg aldosterone)
        1. ­ sodium reabsorption
        2. stimulated by angiotensin II and high plasma K
        3. negatively feeds back onto CRH and ACTH secreting cells
      3. Atrial Natriuretic Peptide (ANP)
        1. Decreases Na (and therefore water) reabsorption
        2. Released by the atrium of the heart (in response to high venous pressures)
      4. Parathyroid hormone (PTH / parathormone)
        1. Secreted by the parathyroid glands in response to low plasma Ca2+
        2. Increases plasma Ca2+ three ways
          1. Removes calcium from the bone
          2. Increases reabsorption from the kidneys
          3. Increases absorption from the intestines
        3. Decreases plasma phosphate levels
        4. Calcitrol (steroid-like substance from vitamin D) - similar to PTH in action
      5. Calcitonin
        1. Secreted by the thyroid in response to high plasma Ca2+
        2. Decreases plasma Ca2+ by replacing Ca2+ in the bone
        3. Increases plasma phosphate levels
        4. No direct feedback between PTH and calcitonin: both rely completely on plasma Ca2+ levels
    3. Reproductive Hormones
      1. Steroid sex hormones in males
        1. FSH (follicle stimulating hormone) - stimulates Sertoli cells
          1. Spermatogenesis
          2. Synthesize androgen-binding protein
          3. Synthesize inhibin
        2. Androgens (testosterone)
          1. Secreted by Leydig cells
          2. Negative feedback to hypothalamus (GnRH) - inhibin has negative feedback on GnRH as well
          3. Responsible for primary and secondary sex characteristics
          4. Promotes general growth and protein synthesis (reason for larger muscles)
          5. Causes aggressive behaviors and sex drive
      2. Steroid sex hormones in females
        1. Testosterone - sex drive in females (women in their 20's and 30's produce more testosterone than estrogen)
        2. Estrogens
          1. Secreted by maturing follicle and placenta
          2. Responsible for primary and secondary sex characteristics
          3. Regulatory role in reproductive cycle
        3. FSH - stimulates development of follicles
        4. LH - Luteinizing hormone
          1. LH surge causes final maturation and rupture of follicle/s
          2. Causes the development of ruptured follicle into corpus luteum
        5. Progesterone
          1. Secreted by the corpus luteum during later half of cycle and for the first 1/3 of pregnancy
          2. Secreted by the placenta during the last 2/3 of pregnancy
          3. Prepares the endometrial lining for pregnancy and helps maintain pregnancy
        6. CG - chorionic gonadotropin
          1. Secreted by the placenta about one day after implantation (3-5 days after fertilization)
          2. Maintains corpus luteum so that it will continue to produce progesterone
      3. Parturition and Lactation
        1. Oxytocin
          1. Stimulated by cervical distension and suckling
          2. Causes the contraction of smooth muscle in mammary glands and the uterus
        2. Prolactin
          1. Stimulated by suckling
          2. Causes the synthesis of milk
  5. Hormonal Action in Invertebrates - insects
    1. Required for molts and maturation from larva to adult
    2. Five major hormones
      1. Prothoracicotropic Hormone (PTTH)
        1. Produced by the neurosecretory cells in the brain
        2. Stimulates the prothoracic gland to produce a -Ecdysone
      2. Ecdysone -
        1. Produced by prothoracic gland and ovarian follicle
        2. Increases RNA, protein, mitochondria, and endoplasmic reticulum synthesis
        3. Promotes secretion of new cuticle; induces molting
      3. Juvenile Hormone
        1. Produced by corpora allata (similar to anterior pituitary)
        2. In larva stage, promotes larval structures and inhibits metamorphosis
        3. In adult, stimulates synthesis and uptake of yolk proteins; activates ovarian follicles and sex accessory glands
      4. Eclosion Hormone
        1. Produced by neurosecretory cells in brain
        2. Causes adult to emerge from pupa/ cocoon
      5. Bursicon -
        1. Produced by neurosecretory cells in brain and nerve cord
        2. Promotes cuticle development; hardens cuticle after new molts