Lecture video

Overview

This lecture covers the endocrine system, focusing on how hormones are secreted, how they interact with target cells, the mechanisms of hormone action, regulation of hormone levels, and common hormone-related disorders.

Endocrine System Overview

• The endocrine system, like the nervous system, integrates and coordinates the functions of organs and organ systems.
• It regulates specific body functions such as fluid and electrolyte balance, reproduction, and metabolism.
• Endocrine glands secrete hormones directly into the bloodstream.
• Glands can be unicellular or multicellular and may develop from either epithelial or neural tissue.
• The system involves complex interactions between endocrine glands, hormones, and the target cells they control.

Hormones and Target Cells

• Hormones are chemical messengers secreted by endocrine glands into the blood, which transports them throughout the body.
• Only target cells with specific receptors for a hormone will respond to it.
• The binding of a hormone to its receptor causes a change in the activity of the target cell.
• Receptors for hormones can be located in the cell membrane, cytosol, or nucleus.
• Each cell type contains receptors for different sets of hormones.
  • Some hormones, like thyroid hormone, affect nearly all cells (all cells have receptors for them).
  • Others, like FSH, act only on specific cells (e.g., in the ovaries and testes).

Hormone Receptors and Sensitivity

• The number of hormone receptors on a cell determines its sensitivity to that hormone.
• The number of receptors can change over time:
  • Up-regulation: an increase in receptor number, making the cell more sensitive to the hormone.
  • Down-regulation: a decrease in receptor number, making the cell less sensitive.
• Changes in receptor number allow cells to adjust their responsiveness to hormones as needed.

Hormone Mechanisms: Hydrophilic vs. Hydrophobic

• Hydrophilic (amino acid-based) hormones:
  • Most are large and polar, so they cannot diffuse through the plasma membrane.
  • Their receptors are transmembrane proteins with binding sites on the cell surface.
  • When the hormone binds, it triggers changes inside the cell without entering it—a process called signal transduction.
  • Two main types of hydrophilic hormone receptors:
    • Kinase receptors: When activated by hormone binding, the intracellular kinase enzyme triggers a cellular response (e.g., insulin receptor).
    • Second messenger systems: Hormone binding activates a G protein, which then activates a membrane-bound enzyme. This enzyme produces a second messenger (like cyclic AMP), which amplifies the signal and activates intracellular enzymes (e.g., protein kinase).
      • The cAMP system: Hormone → receptor → G protein → adenylate cyclase → cAMP → protein kinase activation → cellular response. cAMP is inactivated by phosphodiesterase to stop the response.
• Hydrophobic (lipid-soluble) hormones:
  • These hormones (e.g., steroids) can diffuse through the cell membrane.
  • Once inside, they bind to intracellular receptors in the cytosol or nucleus.
  • The hormone-receptor complex binds to DNA, activating gene transcription to mRNA.
  • mRNA is translated into proteins by ribosomes, and these proteins are the cellular response.
  • Some hydrophobic hormones may have additional mechanisms of action.

Amplification and Regulation of Hormone Secretion

• Amplification: A single hormone-receptor interaction can trigger a large cellular response. One hormone molecule can activate many enzymes or produce many second messengers, leading to thousands of cellular effects.
• Regulation of hormone secretion:
  • Hormone secretion is not constant; it is adjusted to meet the body's needs.
  • Three main control mechanisms:
    • Negative feedback: High hormone levels or their effects suppress further secretion. For example, high blood glucose triggers insulin release, which lowers glucose and then suppresses further insulin secretion.
    • Neural control (neuroendocrine reflexes): The nervous system stimulates hormone secretion in response to specific stimuli. For example, the milk let-down reflex: sensory input from the nipple triggers oxytocin release, causing milk ejection.
    • Rhythmic release (biological rhythms): Many hormones are released in rhythmic patterns, often circadian (about 24 hours), controlled by the brain.

Biological Rhythms and Hormone Release

• Circadian rhythms regulate hormone secretion in roughly 24-hour cycles.
• The main biological clock is the suprachiasmatic nucleus (SCN) in the hypothalamus.
  • SCN cells produce clock proteins in a daily cycle; as these proteins accumulate, they inhibit their own production, and are then broken down, repeating every 24 hours.
  • The SCN is reset by light signals from melanopsin-containing retinal ganglion cells, which send information about light and dark directly to the SCN (entrainment).
  • The SCN controls cyclic activity in other brain regions and regulates melatonin secretion from the pineal gland.
  • Melatonin is released into the blood and helps synchronize clocks in other organs.

Hormone Interactions

• Permissiveness: One hormone increases the number of receptors for a second hormone, making the cell more responsive to the second hormone (e.g., thyroid hormone increases beta-1 receptors in the heart, enhancing catecholamine effects).
• Antagonism: One hormone decreases the number of receptors for another hormone, reducing the cell's responsiveness (e.g., progesterone reduces estrogen receptors in the uterus during pregnancy).

Hormone Concentration Factors

• The concentration of a hormone in the blood at any time depends on four main factors:
  1. Rate of secretion: How much hormone is released by the gland.
  2. Metabolic activation: Some hormones must be chemically altered after secretion to become active (e.g., thyroid hormone, testosterone).
  3. Binding to transport proteins: Most hydrophobic hormones are carried in the blood bound to transport (binding) proteins. Only free (unbound) hormone can leave the blood and act on target cells. The balance between bound and free hormone depends on hormone and transport protein levels.
     • For example, over 99.5% of thyroid hormone is bound, leaving less than 0.5% free to act.
  4. Inactivation and excretion: Hormones are removed from the blood by breakdown in the liver or excretion in urine. Only active hormones can affect target cells.

Hormone Disorders

• Hormone disorders are common health problems (e.g., diabetes, thyroid disorders).
• Hyposecretion: Too little hormone is produced.
• Hypersecretion: Too much hormone is produced.
• Primary disorder: The problem is in the hormone-secreting gland itself (e.g., tumor in the thyroid causing excess hormone).
• Secondary disorder: The problem is in another organ that affects the gland (e.g., pituitary damage causing low thyroid hormone).
• Disorders can also result from abnormal receptor numbers or function in target cells (e.g., type 2 diabetes can involve decreased insulin receptors, so cells do not respond even if insulin levels are normal).

Key Terms & Definitions

• Endocrine Gland: Organ that secretes hormones into the bloodstream.
• Hormone: Chemical messenger from an endocrine gland that affects target cells.
• Target Cell: Cell with a specific receptor for a hormone.
• Receptor: Protein that binds a hormone to initiate a response.
• Up-regulation: Increase in hormone receptor number on a cell.
• Down-regulation: Decrease in hormone receptor number on a cell.
• Kinase Receptor: Membrane receptor with an attached enzyme that activates a cell response.
• Second Messenger: Intracellular molecule that conveys the signal from hormone binding.
• Amplification: Process where one hormone triggers many cellular effects.
• Negative Feedback: Mechanism where the output reduces its own production.
• Suprachiasmatic Nucleus (SCN): Hypothalamic region controlling circadian rhythms.
• Permissiveness: Hormone interaction that increases sensitivity to another hormone.
• Antagonism: Hormone interaction that decreases sensitivity to another hormone.
• Hyposecretion/Hypersecretion: Underproduction or overproduction of a hormone.
• Primary/Secondary Disorder: Issue originating in the gland itself or in another organ.

Action Items / Next Steps

• Review the mechanisms of hormone action, including kinase receptor and second messenger pathways.
• Study the regulation of hormone secretion and feedback loops in detail.
• Prepare for upcoming discussions on specific hormones and related disorders in future lectures.