Introduction to hormones

Introduction to hormones

1. Learning objectives:

   • overview of endocrine, paracrine and autocrine signals
   • overview of peptide, steroid and small molecule hormones
   • hormones of metabolic (glucose) homeostasis; glucagon, adrenalin, insulin and glucocorticoids
   • importance of receptors as mediators of hormone action
   • principle of signal transduction and amplification

2. Endocrinology

   • Hormones are the chemical messengers of the endocrine system (greek-set in motion)
   • study of communication within a living organisms by means of hormone
   • Classic hormone description:
     • chemical messenger secreted from glands, emptied directly into circulation and transported by the blood some distance to alter function of the target organ
       • today's definition - blood-bourne communication = just one aspect of the endocrine system

3. Hormonal communication

   • Hemocrine - often referred to as 'endocrine'
     • straight from cells to blood vessels - blood vessel transports to target cell
   • Autocrine - produces hormone affecting itself/it's own receptors
   • Paracrine (neurocrine if neuronal cells)
     • Produces hormone affecting cell directly adjacent to itself
   • Solinocrine - lots of cells producing hormone into a luminal space
   • General functions:
     • single hormone = single function
       • rare e.g. erythropoietin on HB SYNTHESIS in erythrocytes
     • single hormone = multiple actions
       • thyroid hormone on CHO METABOLISM, bone turnover, enzyme synthesis
     • multiple hormones = single function
       • regulation of LACTATION by prolactin, corticosteroids, thyroxin, sex steroids
   • Hormone action:
     • concentration in ECF very LOW (10^-9 -> 10^-11)
     • unique recognition bu receptors at target tissue
       • receptors can be on CELL SURFACE, CYTOSOLIC or in NUCLEUS
     • Hormones can circulate either FREE or BOUND to a binding protein
       • resevoir/pool of hormone to avoid fluctuations
         • extend half lives
         • STEROIDS - insoluble so need carrier to circulate

4. Classes of hormones

   • Peptide hormones
     • varying sizes - small peptides e.g. TRH - large protein e.g. INSULIN
   • Amino acid derivatives
     • e.g. T3/T4 - tyrosine derived
       • T3 = 2x tyrosine + 3I. T4= 2x tyrosine + 4I.
   • Steroid hormones
     • cholesterol-derived e.g. corticosterone
       • glucocortico-steroids, mineralo-corticosteroids, progesterone etc.
   • Signal transduction
     • G-protein complex coupled to receptor - hormone binds to receptor = phosphorylation and activation of G-protein complex = alteration and activation of cell funcition
       • Initiates secondary messaging in cell -> cascade -> target cell carries out desired funciton
       • PEPTIDE
     • STEROID
       • Receptor internal - within cytoplasm or nucleus
         • Steroid diffuses into the cell - binds to receptor in cytosol, or nucleus - activates/inhibits actovation of genes and transcription of proteins
     • AMINO ACID DERIVED
       • similar to steroid hormones, but receptor is ALWAYS NUCLEAR
         • e.g. Thyroid hormone

5. Peptide vs Steroid hormones

   • Property
     • Storage pools
       • Interaction w/in cell membrane
         • Receptor
           • Action
             • Response time
   • Steroid
     • None
       • Diffusion through cell membrane
         • In cytoplasm or nucleus
           • Regulation of gene transcription
             • Hours to days
   • Peptide
     • Secretory vesicles
       • Binding to receptor on cell membrane
         • On cell membrane
           • Signal-transduction cascades affect a variety of processes
             • Seconds to minutes

6. Control of release of hormones

   • Feedback mechanisms
     • Sensory send hormone -> target -> hormone produced by target 1, activate target 2 and allosterically inhibits sensor
       • e.g. sensory = B-cell producing INSULIN. Target 1 = Store glucose producing GLUCOSE. Target 2 = brain.
   • Tropic hormone, e.g. thyroid releasing hormone
   • Neuronal control, e.g. adrenaline
     • Neuronal control
       • e.g. epinephrine (adrenaline) release from medulla
         • CNS synapses with peripheral nerve and proximal ganglia of ADRENAL MEDULLA = stimulated epinephrine production
   • CIRCADIAN or PULSATILE release
     • Circadian = dependant on daylight, e.g. cortisol
     • Pulsatile release, e.g. growth hormone during sleep

7. Tropic hormones

   • stimulate release of another hormone from other endocrine glands
   • e.g. TRH - thyroid releasing hormone produced by hypothalamus, stimulates anterior pituitary to produce TSH - thyroid stimulating hormone
     • TSH in turn stimulates thyroid gland to produce T3/T4
   • have a growth effect on cells/tissues
     • Hyperplasia - increasing cell number or hypertrophy - increasing cell size or both

8. Nervous system vs Endocrine system

   • Property
     • Nervous system
       • Endocrine System
         • Range of molecules/receptors
           • Slow
             • Slow
               • Slow
                 • Limited
                   • None
                     • Yes
       • Location, Range of transmitters
         • Short to long range
           • Slow to fast
             • Fast
               • High
                 • High
                   • High
     • Specificity
       • communication over a range of distances
         • speed of communication
           • speed of activation/termination
             • integration with other responses
               • Acquisition of new responses or behaviours
                 • Susceptibility to injury or disease

9. Hypothalamus-pituitary axis

   • hypopophyseal portal circulation
     • Neuronal and glandular tissue
       • Anterior, posterior and intermediate lobe
       • optic chasma
   • ANTERIOR LOBE: Hypothalamus = Hypothalamic hormone -> HYPOPOPHYSEAL PORTAL circulation -> anterior lobe hormone-> circulation
   • POSTERIOR LOBE: Hypothalamus = posterior lobe hormone -> AXONAL transport -> posterior lobe
   • Nuclei of hypothalamus - Neuroendocrine function
     • neuroendocrine cells reside in the nuclei of the hypothalamus
     • Control of levels of circulating:
       • Hormones
       • Metabolites
       • Nutrients
       • Electrolytes
     • Stress, cold, trauma, hunger, pain, neural reflex -> sensory information provided
       • The hypothalamus is a focus point for information on internal well being
         • Hormone production and the pituitary gland

10. Hypothalamus hormones

    • GnRH
      • stimulatory effect on pituitary = FSH/LH produced by gonadotrophs
    • GHRH
      • stimulates somatotroph = GH production in pituitary
    • SS
      • inhibitory effect on pituitary= somatotroph produces GH
    • TRH
      • stimulatory effect on thyrotoph in pituitary = TSH production
    • dopamine
      • inhibitory effect on lactotroph of pituitary = PROLACTIN release
    • CRH
      • stimulatory on pituitary = corticotroph porduces ACTH
    • Axons -> posterior pituitary = AVP and OXYTOCIN
      • POST PIT
    • ANT PIT

11. Posterior pituitary: OXYTOCIN

    • 1. during labour to cause contraction of uterus
    • 2. during lactation essential for milk let-down
    • Activation of stretch-sensitive sensory cells feeds back to hypothalamus via spinal cord - NOT HORMONAL feed back but NEURAL
    • Gravid uterus = stretch receptors = spinal cord = PVN & SON = posterior pituitary = OXYTOCIN to UTERUS
      • Hypothalamic nuclei
        • PVN - paraventricular nucleus
        • SON - supraoptic nucleus

12. Posterior pituitary hormones

    • Regulation - secretory stimulus, two REFLEX MECHS
      • Increased = plasma osmolarity. Decreased = plasma volume
    • Clinical abnormalities
      • DIABETES INSIPIDUS
        • chronic excretion of large volumes of dilute urine
        • Thirst caused by hyperosmolarity
        • Disruption of AVP production (pituitary tumours or traumatic injury to the skull)
    • Volume receptors = veins, atria, carotids
      • osmo-receptors = hypothalamus

13. EG: control of thyroid production

    • Hypothalamus produces TRH - thyroid releasing hormone
      • TRH - hypophyseal portal system - ANTERIOR pituitary
        • Thyrotrophs in ant pit produce TSH - thyroid stimulating hormone
          • TSH leaves pituitary -> Thyroid gland

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