Untitled Flashcard Set

Endocrine System

Cell-Cell Communication

• Overview:
     - Outgoing signals lead to physiological responses in other cells.
     - Signal Transduction: The conversion of an impulse or stimulus into another physical or chemical form, affecting cell behavior through intracellular signaling molecules.

Receptors Recognize a Signal

1. Cell-Surface Receptors:
      - Located in the plasma membrane.
      - Bind large, hydrophilic extracellular signal molecules, initiating a physiological response by altering cellular functions.

2. Intracellular Receptors:
      - Located within cells, primarily in the nucleus.
      - Bind small, hydrophobic signal molecules that can cross the plasma membrane.

Signaling: Fast or Slow

• Fast Signaling (< seconds to minutes):
     - Involves altered protein functions.
     - Proteins may activate or inhibit quickly in response to signals.

• Slow Signaling (minutes to hours):
     - Involves altered protein synthesis through changes in gene expression.
     - Stimulates growth, cell division, and other processes over longer periods.

Mechanism Examples

1. Indirect Control of Testosterone Synthesis:
      - Hormones like luteinizing hormone (LH) stimulate the production of second messengers that activate enzymes for testosterone production from cholesterol.

2. Example of Hormonal Signal Integration:
      - Testosterone influences physiological behavior and anatomy as it is secreted into the bloodstream.

General Principles of Cell Signaling

• Signals can act over varying distances (long or short range).

• A limited set of signals can produce various cell behaviors.

• Responses can be fast or slow based on the type of receptor involved.

• Cell-surface receptors relay extracellular signals through intracellular pathways.

• Signaling proteins can act as molecular switches.

Communication in the Body

• Hormones:
     - Transported by the bloodstream, influencing distant physiological responses continuously.

• Paracrines:
     - Local hormones secreted to nearby cells through diffusion, affecting local tissue functions (e.g., growth factors).

• Neurotransmitters:
     - Released from neurons across synaptic clefts, facilitating rapid communication between nerve cells.

• Contact-Dependent Signals:
     - Involved in communication through gap junctions where signal molecules pass directly from one cell to another.

Exocrine vs. Endocrine Glands

Exocrine Glands

• Secrete products through ducts onto epithelial surfaces (e.g., skin, digestive tract).

• Examples include glands that facilitate digestion.

Endocrine Glands

• Do not use ducts; they have a rich capillary network allowing for hormone secretion directly into the blood.

• These glands alter metabolism and have significant systemic effects.

Neuroendocrine Cells

• Hybrid cells possessing features of both neurons and endocrine cells (e.g., adrenal medulla and hypothalamus).

• Function by converting electrical signals from neurons into hormonal signals via hormone secretion into the bloodstream.

Overview of Hormones and Endocrinology

• Endocrinology is defined as the study of the endocrine system, including the disorders and treatments associated with hormonal imbalances.

• Endocrine glands are a collection of organs and tissues that produce and secrete hormones, influencing various bodily functions.

Names and Abbreviations of Hormones

Hypothalamus & Pituitary Gland

• The hypothalamus is a critical controller but does not act as a single master endocrine center.

• It manages a broad range of functions such as hunger, thirst, temperature regulation, sex drive, childbirth, and the stress response.

Structure of the Pituitary Gland

• Located beneath the hypothalamus, connects via the infundibulum.

• Has two divisions, anterior and posterior:
     - Anterior Pituitary (Adenohypophysis):
       - Composed of glandular tissue that secretes several hormones regulated through a portal vein by hypothalamic hormones.
     - Posterior Pituitary (Neurohypophysis):
       - Composed of neural tissue that stores hormones produced from hypothalamic neuroendocrine cells.

Hormones of the Hypothalamus

• Total 8 hormones produced:
     - 2 are stored in the posterior pituitary.
     - 6 regulate the anterior pituitary’s function.
     - Releasing hormones: Stimulate hormone release from anterior pituitary (e.g., GHRH).
     - Inhibiting hormones: Suppress hormone production by anterior pituitary (e.g., somatostatin).

Hypothalamus Hormones (Table 17.3)

Anterior Pituitary Hormones

1. Follicle-stimulating hormone (FSH)
      - Stimulated by: GnRH
      - Target: Ovaries and testes
      - Function: Follicle development and sperm production.

2. Luteinizing Hormone (LH)
      - Stimulated by: GnRH
      - Target: Ovaries and testes
      - Function: Ovulation and corpus luteum formation; stimulates testosterone secretion.

3. Thyroid-stimulating Hormone (TSH)
      - Stimulated by: TRH
      - Target: Thyroid gland
      - Function: Stimulates growth and secretion of thyroid hormones.

4. Adrenocorticotropic Hormone (ACTH)
      - Stimulated by: CRH
      - Target: Adrenal cortex
      - Function: Increases secretion of glucocorticoids.

5. Prolactin (PRL)
      - Stimulated by: TRH
      - Target: Mammary glands
      - Function: Stimulates milk production.

6. Growth Hormone (GH)
      - Stimulated by: GHRH
      - Target: Tissues throughout the body
      - Function: Promotes growth and mitosis. Also known as somatotropin.

Posterior Pituitary Hormones

1. Antidiuretic Hormone (ADH)
      - Target: Kidneys
      - Function: Concentrates urine, conserves water, prevents dehydration. Also known as vasopressin.

2. Oxytocin (OT)
      - Target: Reproductive tissues and the brain
      - Function: Stimulates contractions, milk ejection, and promotes maternal behaviors.

Examples of Hormonal Responses

1. Stress response:
      - Anterior pituitary releases ACTH, stimulating cortisol release from adrenal glands for tissue repair.

2. Dehydration response:
      - When water concentration is low, hypothalamic receptors trigger ADH release from the posterior pituitary, leading kidneys to reabsorb water.

Control of Pituitary Glands

• Feedback Mechanisms:
     - Hormone production is regulated by negative feedback from target organs.
     - Brain continuously monitors body conditions, influencing the pituitary gland's hormone release.
     - Hormonal secretions may vary based on physiological demands, such as stress or pregnancy.
     

Other Organs in the Endocrine System

• Thyroid, Parathyroid, Adrenal, Pancreas, Gonads.

Thyroid Gland

• Function: Manage basal metabolic rate (BMR) through TRH secretion from the hypothalamus.

• Cells:
     - Follicular cells secrete thyroid hormones (TH) in response to TSH.
     - Parafollicular cells secrete calcitonin, which increases bone formation.

Parathyroid Glands

• Function: Secrete parathyroid hormone (PTH) when blood calcium levels are low.

• Actions: Stimulates osteoclasts and promotes calcium reabsorption into the blood.

• Regulation: Independent from the pituitary, directly monitoring blood calcium levels.

Adrenal Glands

1. Adrenal Medulla:
      - Contains neuroendocrine cells; responds to stress and stimulates the release of epinephrine and norepinephrine, influencing fight-or-flight responses.
      

2. Adrenal Cortex:
      - Secretes various steroid hormones, primarily corticosteroids, which include mineralocorticoids (like aldosterone for blood pressure) and glucocorticoids (like cortisol for metabolic regulation).

Pancreas

• Pancreatic Islets:
     - Alpha cells (20%): Secrete glucagon to raise blood glucose.
     - Beta cells (70%): Secrete insulin to lower blood glucose levels.
     - Delta cells (5%): Secrete somatostatin, which inhibits stomach acid secretion.

Gonads

• Both endocrine and exocrine functions:
     - Ovaries: Produce estrogen and progesterone for menstrual regulation and pregnancy support.
     - Testes: Produce testosterone, influencing development and sex drive.

Endocrine System II

Page 2: Objectives

• Identify chemical classes hormones belong to.

• Describe how hormones are produced and sent to target cells.

• Explain how cells regulate their sensitivity to hormones.

• Differentiate between hyposecretion and hypersecretion.

• Describe common diseases associated with the endocrine system.

• Explain how the common endocrine diseases produce their symptoms.

Page 3: Hormone Chemistry

• Three Chemical Classes of Hormones:
    1. Steroids:
       - Derived from cholesterol.
       - Examples include:
         - Sex steroids (e.g., progesterone, testosterone).
         - Corticosteroids (e.g., cortisol).
         - Mineralocorticoids (e.g., aldosterone).
    2. Monoamines:
       - Synthesized from amino acids.
       - Examples include:
         - Dopamine.
         - Epinephrine.
         - Norepinephrine.
         - Melatonin.
         - Thyroid hormones (TH).
    3. Peptides:
       - Composed of 3 to 200+ amino acids.
       - Examples include:
         - Releasing and inhibiting hormones from hypothalamus.
         - Most pituitary hormones.
         - Insulin.

Page 4: Hormone Chemistry Continued

• Three Chemical Classes (reiterated for clarity):
    1. Steroids
    2. Monoamines
    3. Peptides

Page 5: Hormone Synthesis

• Steroids:
    - Different based on functional groups attached to the four-ring steroid backbone.
    - Synthesized in the ovaries, testes, and adrenal cortex.

• Monoamines:
    - Example: Tryptophan → melatonin; Tyrosine → Thyroid Hormones (contains 2 tyrosines).

• Peptides:
    - Synthesized like other proteins:
      1. Transcription
      2. Translation
      3. Folding and modification (9 steps total).

Page 6: Hormone Secretion

• Hormones are not secreted constantly:
    - Follow daily (circadian) rhythms, monthly rhythms, or are triggered by physiological stimuli (i.e., a need).

• Types of Stimuli:
    1. Neural Stimuli:
       - Nerve fibers stimulate hormone release.
       - Example: Release of epinephrine and norepinephrine from adrenal medulla due to sympathetic nervous system activation; childbirth stimulates neurons in hypothalamus leading to oxytocin release.
    2. Hormonal Stimuli: Triggered by other hormones.
    3. Humoral Stimuli: Blood-borne stimuli (e.g., changes in pressure, Ca²⁺ levels, water levels).

Page 7: Hormone Secretion Continued

• Hormonal Stimuli:
    - Tropic effects exemplified by TSH stimulating the release of TH.

• Humoral Stimuli continued from prior page, indicating feedback based on vital signs and concentration levels.

Page 8: Hormone Secretion and Stress Responses

• Short-term Stress Response:
    - Triggered by spinal cord via preganglionic sympathetic fibers and nerve impulses.
    - Involves adrenal medulla secreting catecholamines (epinephrine and norepinephrine).
    - Effects include:
      - Increased heart rate.
      - Increased blood pressure.
      - Bronchodilation (airway enlargement).
      - Glucose release from liver (conversion of glycogen to glucose).
      - Modifications in blood flow (less to digestive system, more to muscles).
      - Increased metabolic rate.

• Long-term Stress Response:
    - Initiated by hypothalamus releasing CRH (corticotropin-releasing hormone).
    - Involves anterior pituitary secreting ACTH.
    - Adrenal cortex secreting steroid hormones leading to:
      - Kidneys retaining sodium and water.
      - Increased blood volume and blood pressure.
      - Conversion of proteins and fats into glucose for energy.
      - Increased blood glucose levels.
      - Suppression of immune system.

Page 9: Stop and Think Questions

• In gonads, what type of hormone would you expect to find production of?

• Production of TH requires thyroglobulin and _______________.

• What type of control does the parathyroid hormone exert on PTH secretion?

Page 10: Next Topics

• Transport of hormones, receptors and targets,

• IP3 and DAG, amplification and modulation of hormones,

• Endocrine disorders.

Page 11: Transport of Hormones

• Transport Mechanisms:
    - Water-Soluble Hormones (mostly monoamines and peptides):
      - Generally hydrophilic; mix easily with blood.
    - Lipid-Soluble Hormones (steroids and thyroid hormones):
      - Hydrophobic; require transport proteins (e.g., albumins and globulins from liver) to travel in blood, enhancing half-life.

Page 12: Stop and Think Questions

• What is an example of a hydrophobic hormone?

• The adrenal medulla has a ________ stress response because it is stimulated by _______.

• An individual with a pituitary tumor exhibiting elevated TSH levels may experience what symptoms?

Page 13: Hormone Receptors

• Function:
    - Stimulate specific target cells via receptor binding.

• Receptors:
    - Comprised of proteins or glycoproteins found on the plasma membrane, in the cytoplasm, or within the nucleus.
    - Diseases can arise from receptor absence (e.g., Type II diabetes).
    - Receptor signaling activates/inhibits various metabolic pathways.

• Pathways:
    - Peptides and monoamines activate second messenger pathways.
    - Steroids and TH primarily influence gene activation.

Page 14: Steroids and TH: Receptors and Actions

• Characteristics:
    - Steroids and TH are hydrophobic.
    - They can diffuse through the plasma membrane, directly affecting the nucleus (most passing directly into it).
    - TH requires active transport to enter the nucleus.

• Actions:
    - Steroid hormones regulate the expression of genes, influencing the activity of ion pumps like Na⁺/K⁺.

• Gene Activation Pathway:
    - Lag time observed due to the processes of transcription and translation triggered by hormones:
      1. Hormone binds to receptor.
      2. ATP is utilized.
      3. Gene expression modifies mRNA and proteins, leading to various metabolic effects.

Page 15: Peptides and Their Mechanisms

• Characteristics:
    - Peptides are hydrophilic and incapable of passing through the plasma membrane.
    - Require cell surface receptors leading to activation of second messenger systems (e.g., cAMP).

• Mechanism Steps:
    1. Hormone-receptor binding activates a G protein.
    2. The G protein activates adenylate cyclase, producing cAMP from ATP.
    3. cAMP activates protein kinases.
    4. Protein kinases phosphorylate enzymes, facilitating or inhibiting metabolic reactions.

Page 16: DAG & IP3 Mechanism

• Activation Process:
    - Receptor activation leads to G protein stimulation of phospholipase, which cleaves phospholipids into two molecules:
      - IP3 and DAG.

Page 17: Effects of DAG & IP3

• DAG:
    - Activates kinases which phosphorylate various enzymes, regulating their activity.

• IP3:
    - Increases intracellular Ca²⁺ levels by:
      - Opening Ca²⁺ channels on the membrane or from the endoplasmic reticulum.
      - Binding to calcium-dependent enzymes or receptors, activating kinases and modifying cell functionality.

Page 18: Example: Oxytocin in Childbirth

• Oxytocin activates receptors in the smooth muscle of the uterus:
    - Process:
      1. Oxytocin binds to its receptor.
      2. IP3 is generated, which promotes Ca²⁺ influx.
      3. Ca²⁺ interacts with calmodulin, leading to muscle contractions.
    - Structure: Calmodulin has two globular ends connected by a long α-helix, each globular end featuring two Ca²⁺ binding sites.

Page 19: Amplification of Hormone Signal

• Mechanism:
    - One molecule of hormone can trigger multiple enzymatic reactions.
    - Example Sequence:
      - 1 epinephrine → 1,000 cAMP molecules.
      - Each cAMP activates 1,000 protein kinases.
      - Each kinase activates 1,000 other enzymes → resulting in 1 billion products from a single epinephrine molecule.
    - This demonstrates how hormones can be effective at very low concentrations.

Page 20: Modulation of Hormones

• Regulatory Mechanisms:
    - Up-Regulation: Increases the number of receptors, enhancing sensitivity to hormones.
    - Down-Regulation: Decreases the number of receptors, reducing sensitivity, commonly seen during prolonged exposure.

Page 21: Hormone Interactions

• Interaction Types:
    - Permissive Effects: One hormone enhances the target organ’s response to another hormone (e.g., estrogen prepares the uterus for oxytocin).
    - Synergistic Effects: Hormones work together to produce a greater effect (e.g., FSH and testosterone affecting sperm production).
    - Antagonistic Effects: One hormone opposes the action of another (e.g., insulin lowers blood glucose while glucagon raises it).

Page 22: Hormone Removal

• Breakdown and Excretion:
    - Hormones mainly broken down by liver and kidneys, then excreted in bile and urine.
    - Other hormones may be cleared by their target cells.

• Metabolic Clearance Rate (MCR):
    - Defined as the rate at which hormones are removed from the blood.
    - A higher MCR correlates with a shorter half-life.
    - Hydrophobic hormones typically have a lower MCR, thereby extending their half-life.

Page 23: Stop and Think Questions

• Identify two additional types of second messengers beyond cAMP.

• Which second messenger is known to stimulate Ca²⁺ release?

• Which hormone listed has the smallest number of target cells: TH, GH, Insulin, or ACTH?

• Classify which hormone(s) are hydrophilic.

Page 24: Endocrine Disorders

• Following pages address specific disorders related to hormonal dysregulation.

Page 25: Growth Hormone (GH) Disorders

• Gigantism:
    - Result of hypersecretion during childhood.

• Pituitary Dwarfism:
    - Caused by hyposecretion during childhood.

• Acromegaly:
    - Occurs from hypersecretion during adulthood.

Page 26: Thyroid Disorders

• Hypothyroidism:
    - Can lead to goiter due to lack of dietary iodine:
      - No iodine = no thyroid hormones produced.
      - Lack of TH fails to inhibit TSH production, resulting in excess TSH stimulating proliferation of thyroglobulin (Tg) which leads to follicle enlargement and neck swelling.

Page 27: Adrenal Disorders

• Cushing Syndrome & Disease:
    - Characterized by excessive cortisol secretion.
    - Etiology may include ACTH hypersecretion, long-term glucocorticoid use (e.g., asthma medication), pituitary tumors, or adrenal cortex tumors.
    - Results in metabolic disruptions such as:
      - Hyperglycemia reminiscent of diabetes.
      - Elevated blood pressure.
      - Muscle and bone loss due to altered protein metabolism.
      - Abnormal fat distribution leading to symptoms like moon face and buffalo hump—known from Cushing’s Awareness Day.

Page 28: Diabetes

• Defined as a condition related to hyposecretion or inefficacy of insulin:
    - Symptoms:
      - Polydipsia (excessive thirst).
      - Polyphagia (excessive hunger).
      - Polyuria (increased urine volume).
      - Hyperglycemia leading to glycosuria (presence of glucose in urine).
      - High levels of ketones resulting in acetone breath and ketonuria.
    - Type I Diabetes: Characterized by very low levels of insulin, constituting 5-10% of cases in the U.S.
    - Type II Diabetes: Marked by insulin resistance due to decreased response of target cells to insulin.