THE ENDOCRINE SYSTEM

1. Major Endocrine Glands

  • Endocrine glands are ductless and secrete hormones directly into the bloodstream.

  • Hormones travel to target cells that contain specific receptor proteins tailored to them.

  • Neurohormones are a type of hormone secreted into the blood by specialized neurons.

  • Hormones significantly influence the metabolism of target organs.

2. Chemical Classification of Hormones

  • Amine hormones:
      - Derived from tyrosine or tryptophan.
      - Examples: Norepinephrine (NE), Epinephrine (E), Thyroxine, and Melatonin.

  • Polypeptide and protein hormones:
      - Chains of amino acids.
      - Examples: Antidiuretic hormone (ADH), Growth hormone (GH), Insulin, Oxytocin, Glucagon, Adrenocorticotropic hormone (ACTH), Parathyroid hormone (PTH).

  • Glycoproteins:
      - Include hormones such as Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), and Thyroid-stimulating hormone (TSH).

  • Steroid hormones:
      - Lipids derived from cholesterol.
      - Examples: Testosterone, Estrogen, Progesterone, Aldosterone, and Cortisol.

3. Prohormones and Prehormones

  • Prohormones are precursors of hormones (e.g., proinsulin).

  • Prehormones are precursors of prohormones (e.g., preproinsulin).

  • Some hormones are initially inactive until activated by target cells (e.g., Thyroxine (T4) is inactive until converted to Triiodothyronine (T3) in target cells).

4. Hormone Interactions

  • A target cell can be responsive to multiple hormones simultaneously.

  • Hormonal interactions may be:
      - Antagonistic: Hormones working in opposition (e.g., insulin and glucagon).
      - Synergistic: Hormones working together to produce a combined effect.
      - Permissive: One hormone enhances the effect of another hormone.

A. Synergistic Effects

  • Occur when multiple hormones produce a combined result.

  • Effects can be:
      - Additive: Both hormones produce the same effect (e.g., epinephrine and norepinephrine affect heart function similarly).
      - Complementary: Each hormone contributes uniquely to a process (e.g., milk production requires Estrogen, Prolactin, and Oxytocin).

B. Permissive Effects

  • Occur when one hormone increases the target cell's responsiveness to another hormone.

  • Example: Estrogen exposure increases the uterus's responsiveness to Progesterone.

  • Example: Increased secretion of PTH enhances intestinal absorption of calcium via Vitamin D3.

C. Antagonistic Effects

  • Hormones that work in opposite directions.

  • Example: Insulin promotes fat storage while Glucagon promotes fat breakdown.

5. Mechanisms of Hormone Action

  • Target cell receptors exhibit:
      - Specificity, high affinity, and low capacity for hormones.

  • Lipophilic hormones:
      - Have receptors located in the target's cytoplasm and/or nucleus since they can diffuse through plasma membranes.
      - Actions involve genomic activity and typically take at least 30 minutes.

  • Hydrophilic hormone receptors:
      - Located on the surface of target cells, operating through second messengers for a rapid effect.
      - Some steroids can also act on surface receptors, termed nongenomic action.

A. Hormones Binding to Nuclear Receptor Proteins

  • Steroid hormones and Thyroxine.

  • Lipid hormones are transported in blood bound to carrier proteins; upon dissociation, they pass through the plasma membrane of the target cell.
      - Receptors for these hormones are called nuclear hormone receptors.

B. Nuclear Hormone Receptors

  • Serve as transcription factors when bound to hormone ligands.

  • Activate the transcription of genes by forming a superfamily that includes steroid family hormones and thyroid hormones (including Vitamin D and Retinoic Acid).

  • Each receptor has:
      - Ligand-binding and DNA-binding domains.

  • They bind the hormone and translocate to the nucleus where they bind to hormone-response elements (HRE) on DNA adjacent to target genes.

1. Mechanisms of Steroid Hormones

  • HRE consists of 2 half-sites; thus, 2 ligand-bound receptors must bind to it.

  • This binding initiates the transcription of target genes.

2. Mechanism of Thyroid Hormone Action

  • The thyroid secretes 90% T4 (Thyroxine) and 10% T3 (Triiodothyronine).

  • Approximately 99.96% of T4 in blood is bound to a carrier protein, Thyroid Binding Globulin (TBG).

  • Only free thyroxine and T3 can enter cells; the bound form acts as a reservoir.

  • T4 is converted to T3 within the target cell, with T3 binding to a nuclear receptor protein.

  • The T3 and receptor form a heterodimer by binding to half-sites at the HRE, stimulating gene transcription.

C. Hormones Using Second Messengers (Non-Steroid Mechanism)

  • These hormones cannot cross the plasma membrane and instead bind to surface receptors.

  • The effect is mediated by second messengers.

Adenylate Cyclase (cAMP) System

  1. Utilized by Epinephrine and Norepinephrine.

  2. Hormone binds to β-adrenergic receptor.

  3. Binding causes G-protein dissociation.

  4. This activates adenylate cyclase.

  5. Adenylate cyclase converts ATP to cAMP.

  6. cAMP activates protein kinase.

  7. Activated protein kinase phosphorylates proteins in the target cell, thereby altering its metabolism.

  8. cAMP activity is terminated by phosphodiesterase.

  9. Some cells can also utilize cGMP for similar actions.

6. The Endocrine Glands

1. Pituitary Gland

  • Located beneath the hypothalamus at the base of the forebrain.
      - Physiologically divided into anterior and posterior lobes.
      - Connected to the hypothalamus via the infundibulum.

  • Anterior Pituitary:
      - Produces its own hormones controlled by the hypothalamus.
      - Secretions include:
        1. Growth hormone (GH): Promotes growth, protein synthesis.
        2. Thyroid Stimulating Hormone (TSH): Stimulates thyroid to secrete T4 and T3.
        3. Adrenocorticotropic Hormone (ACTH): Stimulates adrenal cortex to secrete cortisol and aldosterone.
        4. Follicle Stimulating Hormone (FSH): Stimulates growth of ovarian follicles and sperm production.
        5. Luteinizing Hormone (LH): Triggers ovulation and testosterone secretion in the testes.
        6. Prolactin (PRL): Stimulates milk production in mammary glands.
      - Release regulated by hypothalamic factors and feedback from target gland hormones.
      - Feedback Control:
        - Utilizes the hypothalamic-pituitary-gonad axis which includes:
          - A short feedback loop inhibiting hypothalamus release of the releasing hormone by retrograde hormone flow from the Anterior Pituitary.
          - The negative feedback mechanism involving target gland hormones.
          - Positive feedback such as estrogen inducing LH surge during the menstrual cycle.

Posterior Pituitary

  • Stores and releases hormones (ADH and Oxytocin) produced by the hypothalamus.

  • ADH/Vasopressin: Promotes water conservation by kidneys.

  • Oxytocin: Stimulates uterine contractions during birth and milk ejection.

2. Adrenal Glands

  • Located atop the kidneys, each has an outer cortex and inner medulla.

  • Medulla:
      - Synthesizes and secretes 80% Epinephrine and 20% Norepinephrine, regulated by the sympathetic nervous system.

  • Cortex:
      - Regulated by ACTH, secretes:
        - Cortisol: Inhibits glucose utilization, stimulates gluconeogenesis.
        - Aldosterone: Stimulates kidney reabsorption of sodium (Na⁺) and secretion of potassium (K⁺).
        - Supplementary sex steroids.

Hormonal Effects of Adrenal Medulla

  • Epinephrine effects last 10 times longer than Norepinephrine.

  • Fight or flight response: Elevated respiratory rate, increased heart rate/cardiac output, general vasoconstriction, glycogenolysis, and lipolysis.

3. Thyroid Gland

  • Located below the larynx, secretes T4 and T3 essential for metabolic rate, growth, and development.

  • Composed of thyroid follicles filled with colloid, where iodide (I⁻) is actively transported and converted to I₂ for hormone synthesis.

Thyroid Hormone Production

  • TSH stimulates the hydrolysis of T4 and T3 from thyroglobulin, enabling secretion.

  • Goiter: Occurs in iodine deficiency, where low levels of T4 and T3 prevent negative feedback, leading to elevated TSH which causes thyroid overgrowth.

  • Hypothyroidism: Characterized by low BMR, weight gain, lethargy, and cold intolerance, known as myxedema.

  • Cretinism: Severe mental retardation due to fetal hypothyroidism.

Hyperthyroidism (Grave's Disease)

  • An autoimmune condition where antibodies mimic TSH, overstimulating the thyroid.

  • Symptoms include exophthalmos, weight loss, heat intolerance, irritability, and elevated BMR.

4. Parathyroid Glands

  • Four glands located on the posterior side of the thyroid gland.

  • Secrete Parathyroid hormone (PTH), crucial for regulating blood calcium (Ca²⁺) levels, which increases Ca²⁺ through actions on bones, kidneys, and intestines.

Parathyroid Hormone Release

  • Triggered by low blood Ca²⁺; acts to increase blood Ca²⁺ levels.

5. Pancreas (Islets of Langerhans)

  • Contains clusters of endocrine cells including alpha and beta cells.

  • Alpha cells secrete Glucagon, increasing blood glucose by promoting glycogenolysis and lipolysis.

  • Beta cells secrete Insulin, lowering blood glucose by facilitating cellular glucose uptake and converting glucose to glycogen and fat.