Endocrine System Notes

The Endocrine System

Comparison of Nervous System and Endocrine System

• Similarities:
  • Both systems use chemicals that bind to specific receptors on their target cells.
  • They share many chemical messengers.
    • In the nervous system, these are called neurotransmitters.
    • In the endocrine system, they are called hormones.
  • Both are regulated primarily by negative feedback mechanisms.
  • They share a common goal: to preserve homeostasis by coordinating and regulating other cells, tissues, organs, and systems.

The Endocrine System

• Regulates long-term processes such as:
  • Growth
  • Development
  • Reproduction
• Uses chemical messengers to relay information and instructions between cells.

Organs and Tissues of the Endocrine System

• Hypothalamus
  • Produces ADH, OXT, and regulatory hormones.
• Pituitary Gland
  • Anterior Lobe: ACTH, TSH, GH, PRL, FSH, LH, and MSH
  • Posterior Lobe: Release of oxytocin (OXT) and antidiuretic hormone (ADH)
• Pineal Gland
  • Melatonin
• Thyroid Gland
  • Thyroxine (T4)
  • Triiodothyronine (T3)
  • Calcitonin (CT)
• Parathyroid Glands
  • Parathyroid hormone (PTH)
• Adrenal Gland
  • Medulla: Epinephrine (E), Norepinephrine (NE)
  • Cortex: Cortisol, corticosterone, aldosterone, androgens
• Pancreatic Islets
  • Insulin, glucagon
• Testis
  • See Chapter 21
• Ovary
  • See Chapter 22

Key to Pituitary Hormones

• ACTH: Adrenocorticotropic hormone
• TSH: Thyroid-stimulating hormone
• GH: Growth hormone
• PRL: Prolactin
• LH: Luteinizing hormone
• MSH: Melanocyte-stimulating hormone
• FSH: Follicle-stimulating hormone

Organs with Secondary Endocrine Functions

• Heart
  • Atrial natriuretic peptide (ANP)
  • Brain natriuretic peptide (BNP)
• Thymus (Undergoes atrophy during adulthood)
  • Thymosins
• Adipose Tissue
  • Leptin
• Digestive Tract
  • Secretes numerous hormones involved in the coordination of system functions, glucose metabolism, and appetite.
• Kidneys
  • Erythropoietin (EPO)
  • Calcitriol
• Gonads
  • Testes (male): Androgens (especially testosterone), inhibin
  • Ovaries (female): Estrogens, progesterone, inhibin

Mechanisms of Intercellular Communication (Table 18-1)

• Direct communication
  • Transmission: Through gap junctions
  • Chemical Mediators: Ions, small solutes, lipid-soluble materials
  • Distribution of Effects: Usually limited to adjacent cells of the same type that are interconnected by connexons
• Paracrine communication
  • Transmission: Through extracellular fluid
  • Chemical Mediators: Paracrine factors
  • Distribution of Effects: Primarily limited to a local area, where paracrine factor concentrations are relatively high
• Endocrine communication
  • Transmission: Through the bloodstream
  • Chemical Mediators: Hormones
  • Distribution of Effects: Target cells are primarily in other tissues and organs and must have appropriate receptors
• Synaptic communication
  • Transmission: Across synapses
  • Chemical Mediators: Neurotransmitters
  • Distribution of Effects: Limited to a very specific area; target cells must have appropriate receptors

Hormone Categories

• Groups based on chemical structure:
  • Amino acid derivatives
    • Thyroid hormones
    • Catecholamines
    • Melatonin
  • Peptide hormones
    • Synthesized as prohormones
  • Lipid derivatives
    • Eicosanoids
      • Leukotrienes
      • Prostaglandins
    • Steroid hormones

Hormones - Lipid Derivatives

• Eicosanoids
  • Derived from arachidonic acid, a 20-carbon fatty acid.
  • Paracrine factors that coordinate cellular activities and affect enzymatic processes (such as blood clotting) in extracellular fluids.
  • Some eicosanoids (such as leukotrienes) have secondary roles as hormones.
  • A second group of eicosanoids – prostaglandins – involved primarily in coordinating local cellular activities.
  • In some tissues, prostaglandins are converted to thromboxanes and prostacyclins, which also have strong paracrine effects.
• Steroid hormones
  • Derived from cholesterol
  • Released by:
    • The reproductive organs (androgens by the testes in males, estrogens and progestins by the ovaries in females)
    • The cortex of the adrenal glands (corticosteroids)
    • The kidneys (calcitriol)
  • Because circulating steroid hormones are bound to specific transport proteins in the plasma:
    • They remain in circulation longer than secreted peptide hormones

Hormone Examples by Chemical Structure

• Amino Acid Derivatives
  • Catecholamines
    • Example: Epinephrine
  • Tryptophan Derivatives
    • Example: Melatonin
• Peptide Hormones
• Lipid Derivatives
  • Eicosanoids
    • Example: Prostaglandin E
  • Steroid Hormones
    • Example: Estrogen
    • Thyroid Hormones
      • Thyroxine (T4)

Mechanisms of Hormone Action

• Hormone Receptor
  • Is a protein molecule to which a particular molecule binds strongly
  • Each cell has receptors for several different hormones
  • Cells of different tissues have different combinations of receptors
  • Presence or absence of specific receptor determines hormonal sensitivity
• Down-regulation
  • Presence of a hormone triggers decrease in number of hormone receptors
  • When levels of particular hormone are high, cells become less sensitive to it
  • Type II Diabetes
• Up-regulation
  • Absence of a hormone triggers increase in number of hormone receptors
  • When levels of particular hormone are low, cells become more sensitive to it
  • Type I diabetes
• Secretion and Distribution of Hormones
  • Hormones circulate freely or travel bound to special carrier proteins
  • Free Hormones
    • Remain functional for less than 1 hour
    • Diffuse out of bloodstream and bind to receptors on target cells
    • Are broken down and absorbed by cells of liver or kidneys
    • Are broken down by enzymes in plasma or interstitial fluids
  • Thyroid and Steroid Hormones
    • Remain in circulation much longer because most are “bound”
    • Enter bloodstream
    • More than 99 percent become attached to special transport proteins
    • Bloodstream contains substantial reserve of bound hormones
• Hormone Binding
  • Two possible receptor locations on target cells:
    • Receptor on plasma membrane
      • Requires use of First and Second Messengers
    • Receptor in cytoplasm or nucleus
      • Steroid hormones
      • Thyroid hormones
  • Hormones and Plasma Membrane Receptors
    • Catecholamines and Peptide Hormones
      • Are not lipid soluble
      • Unable to penetrate plasma membrane
      • Bind to receptor proteins at outer surface of plasma membrane (extracellular receptors)
      • Require second messenger inside the cell, while the first messenger (the hormone) stays outside the cell
  • Hormones and Intracellular Receptors
    • Alter rate of DNA transcription in nucleus
    • Change patterns of protein synthesis
    • Directly affect metabolic activity and structure of target cell
    • Include steroids and thyroid hormones
    • Eicosanoids (note these are paracrines – therefore they act locally)
      • Are lipid soluble
      • Diffuse across plasma membrane to reach receptor proteins on inner surface of plasma membrane (intracellular receptors)

Effects of Intracellular Hormone Binding

• Action of steroid hormones
  1. Steroid hormone diffusion through membrane lipids
  2. Binding of hormone to cytoplasmic or nuclear receptors
  3. Binding of hormone–receptor complex to DNA
  4. Gene activation
  5. Transcription and mRNA production
  6. Translation and protein synthesis leading to alteration of cellular structure or activity
• Action of thyroid hormones
  1. Thyroid hormone Transport across plasma membrane
  2. Binding of hormone to cytoplasmic or nuclear receptors
  3. Binding of hormone–receptor complex to DNA
  4. Gene activation
  5. Transcription and mRNA production
  6. Translation and protein synthesis & Binding of receptors at mitochondria and nucleus, leading to alteration of cellular structure or activity & Increased ATP production
• First Messenger
  • Leads to second messenger
  • May act as enzyme activator, inhibitor, or cofactor
  • Results in change in rates of metabolic reactions
• Important Second Messengers
  • Cyclic-AMP (cAMP)
    • Derivative of ATP
  • Cyclic-GMP (cGMP)
    • Derivative of GTP
  • Calcium ions
• The Process of Amplification
  • Is the binding of a small number of hormone molecules to membrane receptors
  • Leads to thousands of second messengers in cell
  • Magnifies effect of hormone on target cell
• G Protein
  • Enzyme complex coupled to membrane receptor
  • Involved in link between first messenger and second messenger
  • G Proteins and cAMP
    • Adenylate cyclase is activated when hormone binds to receptor at membrane surface and changes concentration of second messenger cyclic-AMP (cAMP) within cell
    • Increased cAMP level accelerates metabolic activity within cell
  • G Proteins and Calcium Ions
    • Activated G proteins trigger:
      • Opening of calcium ion channels in membrane
      • Release of calcium ions from intracellular stores
    • G protein activates enzyme phospholipase C (PLC)
      • Enzyme triggers receptor cascade
      • Production of diacylglycerol (DAG) and inositol triphosphate (IP3) from membrane phospholipids
      • May further activate more calcium ion channels through protein kinase C (PKC)
      • Calcium ions may activate calmodulin, which causes further cellular changes

The Hypothalamus

• Provides highest level of endocrine function by integrating nervous and endocrine systems
• Three mechanisms of integration:
  1. Hypothalamic neurons synthesize two hormones that are transported to and released by the posterior pituitary
     • Antidiuretic hormone (ADH)
       • Synthesized by the supraoptic nuclei
     • Oxytocin (OXT)
       • Synthesized by the paraventricular nuclei
  2. Secretes regulatory hormones that control anterior pituitary gland endocrine cells
  3. Contains autonomic centers that directly stimulate the endocrine cells in the adrenal medullae
     • Stimulated in response to sympathetic division activation
     • In response, adrenal medulla releases epinephrine and norepinephrine into bloodstream
• Hypophyseal portal system
  • Capillary networks and interconnecting vessels between the hypothalamus and the pituitary gland (hypophysis, pituitary gland)
  • Regulatory hormones released from the hypothalamus at the median eminence of infundibulum
  • Move from interstitial fluid into fenestrated capillaries
  • Carried to anterior pituitary in portal vessels (portal veins)
  • Form second capillary network within the anterior pituitary
  • Allows hypothalamic hormones to reach target cells in anterior pituitary directly, without mixing and diluting in general circulation
• Two classes of regulatory hormones
  • Releasing hormones (RH)
    • Stimulate hormone synthesis and secretion
  • Inhibiting hormones (IH)
    • Prevent hormone synthesis and secretion

Pituitary Gland

• Pituitary gland or hypophysis
  • Small, oval gland
  • Lies within sella turcica of sphenoid bone
  • Releases nine peptide hormones
    • Seven from anterior lobe (adenohypophysis)
      • Called tropic hormones because they “turn on” other endocrine glands
    • Two from posterior pituitary (neurohypophysis)
    • All nine bind to membrane receptors and use cAMP as 2nd messenger

Hormones of the anterior pituitary gland

• Thyroid-stimulating hormone (TSH) - Thyroid gland
• Adrenocorticotropic hormone (ACTH) - Adrenal gland
• Gonadotropins (FSH and LH) - Ovary / Testis
• Growth hormone (GH) - Musculo-skeletal system
• Prolactin (PRL) - Mammary gland
• Melanocyte-stimulating hormone (MSH)

Hormones of the posterior pituitary gland

• Antidiuretic hormone (ADH) - Kidney
• Oxytocin (OXT) - Uterus

Hormonal Relationships

• Negative feedback
  • Typical control mechanism for hormone secretion
  • Example:
    • Hypothalamic releasing hormone triggers release of hormone by anterior pituitary gland, which triggers release of a second hormone by the target gland
    • Second hormone suppresses secretion of both hypothalamic releasing hormone and pituitary hormone
  • In some cases, both releasing and inhibiting hormones are part of the regulatory process
  • Examples:
    • Growth hormone
      • Somatomedins released by the liver influence hypothalamic hormones
        • Inhibit release of GH–RH
        • Stimulate release of GH–IH
    • Prolactin (PRL)
      • PRL inhibits release of PRF (prolactin-releasing factor)
      • PRL stimulates release of PIH (prolactin-inhibiting factor)

Hormone Interactions

• Cells have more than one type of hormone receptors, so can respond to multiple hormones simultaneously
• Receiving instructions from two hormones at the same time has four possible outcomes:
  • Antagonistic (opposing) effects
  • Additive effects
  • Permissive effects
  • Integrative effects

Types of Hormonal Effects

• Antagonistic Effects
  • Hormone 1 causes increased cellular activity, while Hormone 2 causes decreased cellular activity.
• Additive Effects
  • Hormone 1 and Hormone 2 both cause increased cellular activity.
• Permissive Effects
  • Hormone 1 gives permission for Hormone 2 to cause increased cellular activity.
• Integrative Effects
  • Hormone 1 activates enzyme complex 1, while Hormone 2 activates enzyme complex 2.

The Stress Response

• Stress
  • Any physical or emotional condition that threatens homeostasis
  • Stress can be mediated by specific adjustments
    • Example: shivering as a response to drop in body temperature
  • Exposure to a wide variety of stress-causing factors leads to general hormonal and physiological responses
    • Responses called stress response or general adaptation syndrome (GAS)
• Three phases of the stress response
  • Alarm phase
  • Resistance phase
  • Exhaustion phase

Phases of the Stress Response

• Alarm Phase (“Fight or Flight”)
  • Brain stimulates sympathetic activation and the adrenal medulla.
  • Epinephrine and norepinephrine are released.
  • Immediate short-term responses to crises:
    • Increased mental alertness
    • Increased energy use by all cells
    • Mobilization of glycogen and lipid reserves
    • Changes in circulation
    • Reduction in digestive activity and urine production
    • Increased sweat gland secretion
    • Increased heart rate and respiratory rate
• Resistance Phase
  • Long-Term Metabolic Adjustments
    • Mobilization of remaining energy reserves: Lipids are released by adipose tissue; amino acids are released by skeletal muscle
    • Conservation of glucose: Peripheral tissues (except neural) break down lipids to obtain energy
    • Increased blood glucose concentrations: Liver synthesizes glucose from other carbohydrates, amino acids, and lipids
    • Conservation of salts and water, loss of K^+ and H^+
    • Sympathetic stimulation, Brain, ACTH, Pancreas, Adrenal cortex, Renin-angiotensin-aldosterone system
    • Mineralocorticoids (with ADH), Glucocorticoids, Glucagon, Growth hormone
• Exhaustion Phase
  • Factors That Can Trigger the Exhaustion Phase
    • Exhaustion of lipid reserves and the breakdown of structural proteins as the body’s primary energy source, damaging vital organs
    • Infections that develop due to suppression of inflammation and of the immune response, a secondary effect of the glucocorticoids that are essential to the metabolic activities of the resistance phase
    • Cardiovascular damage and complications that are related to the ADH and aldosterone-related elevations in blood pressure and blood volume
    • Inability of the adrenal cortex to continue producing glucocorticoids, which results in a failure to maintain acceptable blood glucose concentrations
    • Failure to maintain adequate fluid and electrolyte balance