Chapter 17: Endocrine System lecture notes

Fundamentals of the Endocrine System

• General Definition: The endocrine system is a major controlling system of the body that exerts control through the use of hormones.

• Hormonal Communication: Hormones act as chemical signals sent to specific target cells.

• Target Cell Requirements:
      * Target cells must possess a specific receptor for a hormone to respond.
      * If no receptor is present, the hormone will have no effect on that cell.
      * The primary result of hormone binding is a change in the target cell\'s metabolism.

• Mechanism of Distribution: Hormones are secreted by endocrine glands directly into the bloodstream. They circulate throughout the entire body via the cardiovascular system to reach their specific target cells.

Stimuli for Hormone Synthesis and Release

• Three Mechanisms of Stimulation:
      1. Hormonal Stimulation: This occurs when the release of one hormone causes the secretion of another hormone.
          * Example: Thyroid-stimulating hormone ($TSH$) causes the secretion of thyroid hormones ($T3$ and $T4$).
      2. Humeral (Humoral) Stimulation: This occurs when a variable in the blood other than a hormone (such as a nutrient or ion) triggers the release of a hormone.
          * Example 1: Blood calcium level ($Ca^{++}$) fluctuations trigger the release of Parathyroid hormone ($PTH$).
          * Example 2: Blood glucose levels regulate the release of insulin and glucagon.
      3. Nervous Stimulation: This occurs when stimulation by neurons causes a gland to release a hormone.
          * Example: Sympathetic nervous system neurons stimulate the adrenal medulla to release epinephrine and norepinephrine.

Classification and Chemical Categories of Hormones

• Steroid Hormones:
      * Basis: Cholesterol-based molecules.
      * Solubility: Lipid-soluble.
      * Transport/Receptors: They can pass through the cell membrane and bind to intracellular receptors.

• Biogenic Amines (Monoamines):
      * Basis: Modified amino acids derived from tyrosine or tryptophan.
      * Solubility: Generally water-soluble.
      * Exception: Thyroid hormone is a biogenic amine but is lipid-soluble.
      * Receptors: Typically bind to cell surface receptors.

• Proteins (Peptides):
      * Basis: Small chains of amino acids; includes peptides, polypeptides, and glycoproteins.
      * Solubility: Water-soluble.
      * Receptors: Bind to cell surface receptors.

Local Hormones and Eicosanoids

• Local Hormones: Unlike traditional hormones, these are not secreted into the blood. Their effects are localized.
      * Autocrine Effect: The hormone affects the same cell that produced it.
      * Paracrine Effect: The hormone affects nearby or adjacent cells.

• Eicosanoids: A primary group of local hormones.
      * Production: Produced from arachidonic acid, which is derived from phospholipids in the cell membrane.
      * Sub-types: Prostaglandins, thromboxanes, and leukotrienes.
      * Clinical Relevance: Non-steroidal anti-inflammatory drugs ($NSAIDS$) and steroid drugs function by interfering with eicosanoid pathways.

Hormone Transport and Plasma Concentrations

• Lipid-Soluble Hormone Transport:
      * Require carrier proteins for transport through the blood.
      * Some carriers are specific to one hormone, while others are less selective.
      * Bound vs. Unbound Hormone: Only the unbound (free) hormone can bind to a target cell receptor. The bound hormone serves as a "reservoir" in the blood to maintain levels.

• Water-Soluble Hormone Transport:
      * Generally do not require carrier proteins, though some may still be bound.
      * They provide a reservoir of immediately available hormone.

• Factors Influencing Circulating Levels:
      1. Rate of Synthesis: How quickly the gland produces the hormone.
      2. Rate of Elimination:
          * Degradation in the liver.
          * Elimination by the kidneys (excretion).
          * Uptake by target cells.

• Half-Life:
      * Definition: The amount of time required for the level of circulating hormone to be reduced by $50\%$.
      * Water-soluble hormones: Generally have a short half-life.
      * Steroid hormones: Have a longer half-life because carrier proteins protect them and reduce the rate of elimination.

Mechanisms of Hormone Interaction with Target Cells

• Lipid-Soluble Interaction:
      1. Diffuses directly through the target cell membrane.
      2. Binds to an intracellular receptor (in the cytosol or nucleus).
      3. Forms a hormone-receptor complex.
      4. The complex binds to DNA at a specific site called the hormone-response element.
      5. This triggers DNA transcription and subsequent protein synthesis.
      6. The result is a change in the target cell metabolic activity.

• Water-Soluble Interaction:
      * Hormones cannot cross the cell membrane.
      * They require a cell surface receptor and a signal transduction pathway.
      * First Messenger: The hormone itself.
      * Second Messenger: Intracellular signaling molecules triggered by the first messenger.

Signal Transduction Pathways: Second and Third Messengers

• G Protein Activation:
      1. Hormone binds to the receptor.
      2. $GDP$ is released from the G protein.
      3. $GTP$ binds to the G protein, activating it.

• Adenylate Cyclase Pathway:
      1. Activated G protein activates the enzyme adenylate cyclase.
      2. Adenylate cyclase catalyzes the conversion of $ATP$ into cyclic $AMP$ ($cAMP$).
      3. $cAMP$ acts as the second messenger.
      4. $cAMP$ activates protein kinase.
      5. Protein kinase phosphorylates other molecules, causing their activation or inactivation.

• Phospholipase C Pathway:
      1. Activated G protein activates phospholipase C.
      2. Phospholipase C splits into two second messengers: $DAG$ (diacylglycerol) and $IP3$ (inositol triphosphate).
      3. $DAG$: Activates protein kinase.
      4. $IP3$: Increases intracellular calcium ($Ca^{++}$) levels.
      5. Role of $Ca^{++}$: Often acts as a "third messenger." It can activate protein kinases or alter membrane permeability to ions.

Effects and Amplification of Water-Soluble Hormones

• Cellular Actions:
      * Activation or inhibition of specific enzymes.
      * Changes in membrane permeability.
      * Stimulation of growth via cell division.
      * Release of secretions (including other hormones).

• Cascade Effect and Amplification:
      * One single hormone molecule binding to one receptor can lead to the activation or inhibition of millions of molecules within the cell.
      * This amplification allows for a massive response from a small signal.
      * Regulation: Each step of the cascade can be regulated to fine-tune the hormone response.

Regulation of Target Cell Response and Hormone Interactions

• Number of Receptors: Cells can adjust their sensitivity to hormones by changing receptor counts.
      * Up-regulation: Increasing the number of receptors to become more sensitive to low hormone levels.
      * Down-regulation: Decreasing the number of receptors to become less sensitive to high hormone levels.

• Hormone-to-Hormone Interactions:
      * Synergistic: One hormone increases the response or effectiveness of another.
      * Permissive: One hormone must be present for the second hormone to exert its effect.
      * Antagonistic: Two hormones have functional opposite effects (e.g., insulin vs. glucagon).

The Hypothalamus and Pituitary Gland Complex

• The Hypothalamus: Located in the diencephalon; regulates the production of many pituitary hormones and their subsequent pathways (e.g., the $TRH \rightarrow TSH \rightarrow TH$ pathway).

• Anatomy:
      * Infundibulum: The stalk connecting the hypothalamus to the pituitary gland.
      * Secretory Pathways:
          * Anterior Pituitary: Connected via the hypothalamic-hypophyseal portal system (blood vessels).
          * Posterior Pituitary: Connected via the hypothalamic-hypophyseal tract (axons of neurons).

Posterior Pituitary Hormones: Oxytocin and ADH

• Production: These hormones are produced by neurosecretory (neuroendocrine) cells in the hypothalamus.

• Transport: They travel down the axons of the hypothalamic-hypophyseal tract to the posterior pituitary, where they are stored and released into the blood.

• Oxytocin ($OT$):
      * Targets: Smooth muscle in the breast and uterus.
      * Actions: Causes milk ejection (let-down) in the breast and uterine contractions during childbirth. It also has emotional components.

• Antidiuretic Hormone ($ADH$):
      * Targets: Kidneys and thirst center.
      * Stimulus: Secreted when osmoreceptors in the hypothalamus detect high blood osmolarity (concentrated blood).
      * Actions: Concentrates urine by triggering water reabsorption via aquaporins and stimulates the thirst sensation.

Anterior Pituitary Regulatory Hormones

• Hypothalamic Releasing Hormones:
      * $TRH$ (Thyrotropin-releasing hormone): Causes release of $TSH$ (Thyroid-stimulating hormone), which stimulates the thyroid to make $T3$ and $T4$.
      * $PRH$ (Prolactin-releasing hormone): Regulates release of Prolactin ($PRL$).
      * $GnRH$ (Gonadotropin-releasing hormone): Causes release of $FSH$ (Follicle-stimulating hormone) and $LH$ (Luteinizing hormone), controlling reproduction.
      * $CRH$ (Corticotropin-releasing hormone): Causes release of Adrenocorticotropic hormone ($ACTH$), which acts on the adrenal cortex.
      * $GHRH$ (Growth hormone-releasing hormone): Stimulates the release of Growth Hormone ($GH$).

• Hypothalamic Inhibiting Hormones:
      * $PIH$ (Prolactin-inhibiting hormone): Prevents $PRL$ release.
      * $GHIH$ (Growth hormone-inhibiting hormone): Prevents $GH$ release.

• Growth Hormone ($GH$):
      * Targets: Liver, muscle, bone, and adipose tissue.
      * Action: Stimulates overall body growth.

The Thyroid Gland

• Composition: Contains follicular cells and follicles, and parafollicular cells.

• Thyroid Hormone ($T3$ and $T4$):
      * Synthesized by follicular cells.
      * Effects: Increases metabolic rate (calorigenic effect), increases blood pressure ($BP$), heart rate ($HR$), and the strength of heart contractions.

• Calcitonin:
      * Produced by parafollicular cells.
      * Stimulus: Increased blood calcium levels (primarily active in children).
      * Actions (to decrease $Ca^{++}$):
          * Decreased absorption in the gastrointestinal ($GI$) tract.
          * Decreased reabsorption in the kidneys.
          * Decreased osteoclast activity (prevents bone breakdown).

The Parathyroid Glands

• Location: Usually four small glands located on the posterior surface of the thyroid.

• Parathyroid Hormone ($PTH$):
      * Actions (to increase $Ca^{++}$):
          * Increased absorption in the $GI$ tract.
          * Increased reabsorption in the kidneys.
          * Increased osteoclast activity.

The Adrenal Glands

• Location: Superior to the kidneys.

• Adrenal Medulla:
      * Contains chromaffin cells.
      * Secretes epinephrine and norepinephrine.
      * Function: Augments the sympathetic "fight-or-flight" response.

• Adrenal Cortex: Divided into zones producing different steroids:
      * Mineralocorticoids (e.g., Aldosterone): Regulates Sodium ($Na^+$) and Potassium ($K^+$). Influences blood pressure because "water follows sodium."
      * Glucocorticoids (e.g., Cortisol): Known as the stress hormone. Increases release of glucose and fatty acids. It is anti-inflammatory but can dampen the immune system if levels are high for prolonged periods.
      * Androgens: Masculinizing hormones. Easily converted to feminizing hormones. They are a major source of sex hormones prior to puberty.

The Pancreas and Glucose Regulation

• Pancreatic Islets: Clusters of endocrine cells.

• Beta Cells:
      * Secrete Insulin.
      * Stimulus: High blood glucose levels.

• Alpha Cells:
      * Secrete Glucagon.
      * Stimulus: Low blood glucose levels.

Additional Endocrine Organs: Gonads, Thymus, and Kidneys

• Gonads:
      * Ovaries: Produce estrogens and progesterone.
      * Testes: Produce testosterone.

• Thymus: Produces thymic hormones essential for the development and regulation of $T$-cells.

• Kidneys: Produce multiple hormones/enzymes:
      * Calcitriol: Active form of Vitamin D.
      * Erythropoietin: Stimulates red blood cell production.
      * Renin: Part of the blood pressure regulation pathway.

• Other Organs with Endocrine Function: Pineal gland, heart (atrial natriuretic peptide).