5.1 Hormones and their mechanisms of action

Hormones are the body's chemical messengers, orchestrating various physiological processes. They come in different types - peptide, steroid, and amine - each with unique structures and functions. Understanding their classification helps grasp how they work in our bodies.

Hormones act through receptor-mediated and non-receptor-mediated pathways, triggering cellular responses. Their actions are finely tuned by feedback loops, ensuring balance in the body. This intricate system of hormone regulation is crucial for maintaining homeostasis and adapting to changes.

Chemical structure of hormones

Classification of hormones by chemical structure

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• Hormones can be classified into three main categories based on their chemical structure: peptide hormones, steroid hormones, and amine hormones
  • Peptide hormones consist of amino acids and include insulin (regulates blood glucose), growth hormone (stimulates growth and cell reproduction), and oxytocin (involved in childbirth and bonding)
  • Steroid hormones are derived from cholesterol and include cortisol (stress response), aldosterone (regulates blood pressure and electrolyte balance), and sex hormones like estrogen and testosterone (development and regulation of reproductive system)
  • Amine hormones are derived from amino acids and include epinephrine and norepinephrine (fight-or-flight response) and thyroid hormones (regulate metabolism and growth)

Synthesis and regulation of hormones

• The synthesis of hormones occurs in the endocrine glands and involves various enzymatic reactions and modifications specific to each hormone type
  • For example, peptide hormones are synthesized as inactive precursor proteins that undergo post-translational modifications, while steroid hormones are synthesized from cholesterol through a series of enzymatic reactions
• The rate of hormone synthesis is often regulated by feedback loops, where the levels of the hormone itself or its effects on target tissues influence its production
  • Negative feedback loops, such as the hypothalamic-pituitary-thyroid axis, help maintain hormone levels within a narrow range
  • Positive feedback loops, such as the release of oxytocin during childbirth, amplify the hormone response until a critical point is reached

Mechanisms of hormone action

Receptor-mediated pathways

• Receptor-mediated pathways involve the binding of a hormone to a specific receptor protein, which can be located on the cell surface or inside the cell
  • Cell surface receptors are typically associated with hydrophilic hormones, such as peptide hormones (insulin) and catecholamines (epinephrine)
  • Intracellular receptors are usually associated with hydrophobic hormones, such as steroid (cortisol) and thyroid hormones (T3 and T4)
• The hormone-receptor complex triggers a cascade of intracellular signaling events that ultimately lead to changes in gene expression, protein synthesis, or cellular activity
  • For example, the binding of epinephrine to its receptor activates the cAMP second messenger system, leading to the breakdown of glycogen and increased blood glucose levels
  • The binding of steroid hormones to their intracellular receptors forms a complex that acts as a transcription factor, directly influencing gene expression in the nucleus

Non-receptor-mediated pathways

• Non-receptor-mediated pathways involve hormones that can directly influence cellular processes without binding to a specific receptor
  • Examples include the action of insulin on glucose uptake by facilitating the translocation of glucose transporter proteins (GLUT4) to the cell membrane
  • Thyroid hormones can directly influence mitochondrial function by uncoupling oxidative phosphorylation, leading to increased heat production and metabolic rate

Hydrophobic vs hydrophilic hormones

Hydrophobic hormones

• Hydrophobic hormones, such as steroid and thyroid hormones, are lipid-soluble and can easily pass through the cell membrane to bind to intracellular receptors
  • The hormone-receptor complex acts as a transcription factor, directly influencing gene expression in the nucleus
  • The effects of hydrophobic hormones are typically slower in onset but longer-lasting compared to hydrophilic hormones
  • Examples of hydrophobic hormones include cortisol (regulates stress response and metabolism), estrogen (female reproductive development), and testosterone (male reproductive development)

Hydrophilic hormones

• Hydrophilic hormones, such as peptide hormones and catecholamines, are water-soluble and cannot pass through the cell membrane. They bind to cell surface receptors to exert their effects
  • The binding of hydrophilic hormones to their receptors activates intracellular signaling cascades, often involving second messengers like cyclic AMP (cAMP) or calcium ions
  • The effects of hydrophilic hormones are usually rapid in onset but shorter in duration compared to hydrophobic hormones
  • Examples of hydrophilic hormones include insulin (lowers blood glucose), oxytocin (uterine contractions and milk letdown), and vasopressin (regulates water balance and blood pressure)

Feedback loops in hormone regulation

Negative feedback loops

• Negative feedback loops are the most common type, where the effects of a hormone inhibit its own synthesis or release, preventing excessive hormone action
  • For example, high blood glucose levels stimulate insulin secretion, which in turn lowers blood glucose by promoting its uptake and storage. As blood glucose levels decrease, insulin secretion is inhibited
  • The hypothalamic-pituitary-thyroid axis is another example of a negative feedback loop, where thyroid hormones inhibit the release of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) when circulating levels are high

Positive feedback loops

• Positive feedback loops are less common but can be crucial in certain physiological processes, such as the release of oxytocin during childbirth or the LH surge during ovulation
  • In these cases, the effects of the hormone stimulate its own production, leading to a rapid amplification of the response until a critical point is reached
  • During childbirth, the pressure of the baby's head on the cervix stimulates oxytocin release, which causes uterine contractions. These contractions further stimulate oxytocin release, creating a positive feedback loop that continues until the baby is born
• Feedback loops involve the integration of signals from multiple endocrine glands and target tissues, ensuring a coordinated and adaptive response to changes in the internal or external environment
  • For example, the hypothalamic-pituitary-adrenal axis integrates signals from the brain, pituitary gland, and adrenal glands to regulate the stress response
  • The hypothalamic-pituitary-gonadal axis coordinates the actions of the brain, pituitary gland, and gonads to regulate reproductive function and development