Hormones and Their Actions

Chemical Classes of Hormones

• Refers to the different structural categories hormones fall into which affect their synthesis, transport, and mechanism of action.

Synthesis of Steroid Hormones

• Steroid hormones are synthesized from cholesterol.

Hormone Secretion

• Three types of stimuli trigger hormone secretion:

  • Neural stimuli:

    • Nerve fibers stimulate endocrine glands to release hormones.

    • Example: The sympathetic nervous system prompts the adrenal medulla to secrete epinephrine and norepinephrine during stress.

    • Example: In childbirth, uterine stretch receptors send signals to the hypothalamus, leading to oxytocin release.

  • Hormonal stimuli:

    • Hormones from the hypothalamus control secretion by the anterior pituitary gland.

    • Pituitary hormones stimulate other endocrine glands to release hormones like thyroid hormone, sex hormones, and cortisol.

  • Humoral stimuli:

    • Involve blood-borne stimuli.

    • Example: High blood glucose stimulates insulin release.

    • Example: Low blood osmolarity stimulates aldosterone secretion.

    • Example: Low blood calcium stimulates parathyroid hormone secretion.

Hormone Actions on a Target Cell

• Hormones bind to receptors on or in target cells.

Cyclic AMP (cAMP) as a Second Messenger

• cAMP acts as a second messenger to mediate hormone action within the cell.

Modulation of Target-Cell Sensitivity

• Target cells adjust their sensitivity to hormones by changing the number of receptors.

  • Up-regulation: increases the number of receptors, thus increasing sensitivity.

  • Down-regulation: reduces the number of receptors, reducing cell sensitivity.

  • Down-regulation occurs with long-term exposure to high hormone concentrations.

Hormone Interactions

• Most cells respond to multiple hormones, leading to different interactive effects:

  • Synergistic effects: multiple hormones act together for a greater effect.

    • Example: FSH and testosterone on sperm production.

  • Permissive effects: one hormone enhances the target organ's response to a second hormone.

    • Example: Estrogen prepares the uterus for progesterone's action.

  • Antagonistic effects: one hormone opposes the action of another.

    • Example: Insulin lowers blood glucose, while glucagon raises it.

Stress and Adaptation

• Stress: any situation that disrupts homeostasis.

  • Stressors: injury, surgery, infection, intense exercise, pain, grief, depression, anger, etc.

  • The body responds to stress with a general adaptation syndrome (GAS).

  • This typically involves elevated levels of epinephrine and glucocorticoids (especially cortisol).

  • Occurs in three stages: alarm reaction, stage of resistance, and stage of exhaustion.

The Alarm Reaction

• Alarm reaction: the initial response to stress, mediated by the sympathetic nervous system.

  • Involves release of norepinephrine and epinephrine from the sympathetic nervous system and adrenal medulla.

  • Prepares the body for fight or flight.

  • Stored glycogen is consumed.

  • Increases aldosterone and angiotensin levels.

    • Angiotensin helps raise blood pressure.

    • Aldosterone promotes sodium and water conservation.

The Stage of Resistance

• Stage of resistance: provides alternative fuels for metabolism.

  • Occurs after a few hours if the stressor persists and glycogen reserves are depleted.

  • Dominated by cortisol.

  • The hypothalamus secretes corticotropin-releasing hormone (CRH).

  • The pituitary secretes ACTH.

  • Stimulates the adrenal cortex to secrete cortisol and other glucocorticoids.

  • Promotes breakdown of fat and protein into glycerol, fatty acids, and amino acids for gluconeogenesis.

• Cortisol has a glucose-sparing effect, inhibiting protein synthesis to leave free amino acids for gluconeogenesis.

• Adverse effects of cortisol:

  • Depresses immune function.

  • Increases susceptibility to infection and ulcers.

  • Lymphoid tissues atrophy, antibody levels drop, and wounds heal poorly.

Eicosanoids and Other Signaling Molecules

• Paracrine signals: chemical messengers that diffuse short distances and stimulate nearby cells.

  • Histamine: from mast cells in connective tissue; causes relaxation of blood vessels.

  • Nitric oxide: from the endothelium of blood vessels; causes vasodilation.

  • Catecholamines: diffuse from the adrenal medulla to the cortex.

• Autocrine signals: chemical messengers that stimulate the same cell that secreted them.

  • Hepcidin: stimulates the liver cells that secreted it and regulates their release of stored iron into the blood.

• A single chemical can act as a hormone, paracrine, or even neurotransmitter in different locations.

Eicosanoids

• Eicosanoids: an important family of paracrine secretions.

  • Derived from arachidonic acid.

  • Lipoxygenase converts arachidonic acid into leukotrienes.

    • Leukotrienes mediate allergic and inflammatory reactions.

  • Cyclooxygenase converts arachidonic acid to other eicosanoids

    • Prostacyclin: inhibits blood clotting and vasoconstriction.

    • Thromboxanes: stimulate vasoconstriction and clotting.

    • Prostaglandins (PGs): diverse group with diverse roles.

      • Example: PGE relaxes smooth muscle in the bladder, intestines, bronchioles, and uterus; stimulates contraction of blood vessels.

Anti-Inflammatory Drugs

• Cortisol and corticosterone:

  • Steroidal anti-inflammatory drugs (SAIDs).

  • Inhibit inflammation by blocking the release of arachidonic acid and inhibit synthesis of eicosanoids.

  • Disadvantage: produce symptoms of Cushing syndrome.

• Aspirin, ibuprofen, and celecoxib (Celebrex):

  • Nonsteroidal anti-inflammatory drugs (NSAIDs).

  • COX inhibitors, as they block cyclooxygenase (COX).

  • Do not affect lipoxygenase function or leukotriene production.

  • Useful in the treatment of fever and thrombosis.

  • Inhibit prostaglandin and thromboxane synthesis.