W1 L2: Hormone synthesis, secretion and signalling

Synthesis of Amine Hormones

  • Adrenal amines (adrenaline and noradrenaline)
    • Synthesised from tyrosine
    • Stored in cytoplasmic vesicles
  • Thyroid amines (T3 and T4)
    • Synthesised via a multi-component pathway involving the protein thryoglobulin (Tg)
    • Stored as a large precursor → colloid

Synthesis of Steroids

  • Most are synthesised from cholesterol
  • Cells that produce steroid hormones typically contain multiple lipid droplets in their cytoplasm
  • Little storage in endocrine cells
    • de novo synthesis follows cell stimulus
    • (But,) stores of cholesterol present in the cells can be rapidly metabolised

Peptide Hormone Synthesis:

Post-Translational Modifications:

  • To become fully functional, many proteins require further processing after translation.

  • Peptide hormones subject to variety of such modifications

  • Preprohormones:

    • Inactive precursor from single gene
    • Cleaved → active components

  • Dimerisation:

    • Subunits from different genes
    • Combine → active product

Secretion of Thyroid Amines and Steroids

  • Thyroid amines and steroids are lipophilic
    • Diffuse across the cell membrane into the blood, so no active secretory mechanism
    • Once in hydrophilic blood, they are transported bound to plasma proteins
  • Steroids are released immediately after their de novo synthesis
  • Thyroid hormones are only released after they dissociate from their colloid precursor

Secretion of Adrenal Amine and Peptide Hormones: Exocytosis

  • Secretory process for adrenal amines and peptide hormones – Endocrine and neuroendocrine
  • Vesicle contents are released by fusing of the vesicle to the cell membrane
  • Triggered by influx of Ca2+ in many cases; other triggers include cAMP

Hormone Signalling: Introduction to Receptors

  • Inter-cellular signalling molecules regulate target cells by binding to specific proteins →receptors
  • Therefore, hormone receptors are essential for the function of the endocrine system
  • There are many types of receptor, but can be loosely categorised as:
    • membrane-bound receptors (expressed on the external plasma membrane)
    • intracellular receptors (expressed in the cytoplasm)

Membrane-Bound Receptors

  • Mechanism of action for hydrophilic peptide and amine hormones
  • Proteins present in the plasma membrane
  • Many different types, but all have 3 basic domains:
  • Extracellular (binds hormone)
  • Transmembrane
  • Intracellular (often necessary for effects in target cell, e.g. change in enzyme activity)
  • Typically, responses are rapid & cause a change in:
    • membrane permeability (e.g. adrenaline)
    • enzyme activity (e.g. insulin)

Intracellular Receptors

  • Mechanism of action for steroid and thyroid hormones

  • Stimulate gene expression → delayed & prolonged response