Introduction to Endocrinology and Pituitary Hormones

Introduction to Endocrinology

  • Definitions and General Principles:

    • Hormones: Chemical substances released by a cell or group of cells into body fluids that exert some type of physiological "control."
    • Response Time: Functions across a broad spectrum of time, ranging from seconds to minutes (immediate) or months to years (long-term).
    • Primary Functions: The hormonal system controls and regulates:
      • Reproduction.
      • Metabolism and energy balance.
      • Growth and development.
      • General homeostasis, including water and electrolyte balance.

  • Types of Chemical Messenger Systems:

    • Neurotransmitters: Released at synapses.
    • Endocrine hormones: Released into the blood to act on distant tissues.
    • Neuroendocrine hormones: Secreted by neurons into the blood.
    • Paracrines: Act on neighboring cells.
    • Autocrines: Act on the same cell that secreted them.
    • Cytokines and Adipokines: Released by immune or adipose cells.

  • Principal Endocrine Glands and Tissues:

    • Hypothalamus and Pineal gland.
    • Pituitary gland.
    • Thyroid gland and Parathyroid glands (located behind the thyroid).
    • Thymus gland.
    • Pancreas (Islets of Langerhans).
    • Adrenal glands.
    • Kidney.
    • Stomach and Small intestine.
    • Adipose tissue.
    • Ovaries (female) and Testes (male).
    • Placenta.

Hormone Classification, Secretion, and Transport

  • Classes of Hormones:

    1. Proteins and Polypeptides: Long or short chains of amino acids.
    2. Steroids: Derived from lipid cholesterol.
    3. Amine Hormones: Derived from the amino acid tyrosine.

  • Major Endocrine Glands and Their Secretions:

    • Anterior Pituitary: Growth Hormone (GH), Adrenocorticotropin (ACTH), Thyroid-stimulating hormone (TSH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Prolactin.
    • Posterior Pituitary: Antidiuretic hormone (ADH), Oxytocin.
    • Thyroid Gland: Thyroxine (T4T_4), Triiodothyronine (T3T_3), and Calcitonin.
    • Adrenal Cortex: Cortisol, Aldosterone.
    • Parathyroid: Parathyroid Hormone (PTH).
    • Pancreas: Insulin, Glucagon.
    • Ovaries: Estrogen, Progesterone.
    • Testes: Testosterone.
    • Placenta: Human chorionic gonadotropin (hCG), Estrogen, Progesterone, Human somatomammotropin.

  • Secretion Mechanics:

    • Duration of Onset: Norepinephrine acts within seconds-minutes, while GH actions can span months-years.
    • Concentrations: The amount required for control is extremely small, typically ranging from pg/mlpg/ml to mg/mlmg/ml of blood.
    • Feedback Loops:
      • Negative Feedback: Prevents over-activity; utilized by most hormones.
      • Positive Feedback: Causes surges (e.g., Luteinizing hormone surge before ovulation).

  • Transport and Clearance:

    • Solubility and Transport:
      • Water-soluble: Peptides and catecholamines traverse the blood freely.
      • Protein-bound: Steroids and thyroid hormones require transport proteins.
    • Metabolic Clearance Rate (MCR): Defined as the rate of disappearance of hormone from plasma divided by the concentration of hormone in each milliliter of plasma:         MCR=rate of disappearanceplasma concentrationMCR = \frac{\text{rate of disappearance}}{\text{plasma concentration}}
    • Clearance Mechanisms: Hormones are removed by metabolic destruction, tissue binding, excretion by the liver, or excretion by the kidneys.

Mechanisms of Hormonal Action

  • Receptor Types:

    • Ion channel-linked receptors.
    • G protein-linked receptors.
    • Enzyme-linked receptors.
    • Intracellular (cytosol or nucleus) receptors that activate genes.

  • Four Major Second Messenger Systems:

  1. cAMP Signaling Mechanism:

    • Process:
      1. Hormone binds to the receptor.
      2. G protein is activated (GDP→GTPGDP \rightarrow GTP).
      3. G-alpha (GαG_\alpha) subunit binds with adenylyl cyclase.
      4. ATP is converted to cAMP within the cell.
      5. cAMP activates cAMP-dependent kinases.
    • Physiological Responses: Activates enzymes, alters cell permeability, causes muscle contraction/relaxation, initiates protein synthesis, or causes secretion.
    • Examples: TSH, ACTH, LH, Somatostatin.

  2. Cell Membrane Phospholipid Second Messenger System:

    • Process:
      1. Hormone binds to the receptor.
      2. G protein is activated.
      3. GαG_\alpha activates Phospholipase C.
      4. Phospholipase C causes the breakdown of PIP2PIP_2 (phosphatidylinositol 4,5-bisphosphate) into IP3IP_3 (inositol triphosphate) and DAGDAG (diacylglycerol).
      5. IP3IP_3 binds to receptors on the mitochondria or endoplasmic reticulum (ER), mobilizing Ca2+Ca^{2+} release.
      6. DAGDAG activates Protein Kinase C (PKC), leading to protein phosphorylation and cellular responses.
    • Examples: Growth hormone-releasing hormone (GHRH), Oxytocin, Thyrotropin-releasing hormone (TRH).

  3. Calcium-Calmodulin Second Messenger System:

    • Process:
      1. Hormone binds to receptors or calcium channels on the cell membrane.
      2. Receptor undergoes a conformational change, increasing membrane permeability to Ca2+Ca^{2+}.
      3. Ca2+Ca^{2+} enters the cell, increasing intracellular concentration ([Ca2+]i[Ca^{2+}]_i).
      4. Ca2+Ca^{2+} binds with Calmodulin, causing it to undergo a conformational change.
      5. Activated Calmodulin activates or inhibits target proteins and kinases (e.g., calmodulin-dependent protein kinases).
    • Example: Adrenocorticotropic hormone (ACTH).

  4. Transcriptional Pathway:

    • Process:
      1. Lipophilic hormones (steroids) diffuse through the cell membrane; tyrosine derivatives may diffuse to the nucleus.
      2. Hormone binds with an intracellular (cytosolic or nuclear) receptor.
      3. The hormone-receptor complex binds to a specific DNA site called the Hormone Response Element (HRE).
      4. Transcription is initiated, forming mRNA.
      5. mRNA is transported to ribosomes in the rough ER for translation into new proteins.
    • Example: Aldosterone.

The Pituitary Gland (Hypophysis)

  • The Hypothalamus-Pituitary Unit: This unit is the most dominant portion of the endocrine system. It regulates the thyroid, adrenal, and reproductive glands, and controls somatic growth, lactation, milk secretion, and water metabolism.

  • Anatomy:

    • Anterior Pituitary (Adenohypophysis): Connected to the hypothalamus via the superior hypophyseal artery and the hypophyseal portal system.
    • Posterior Pituitary (Neurohypophysis): A neural outgrowth of the hypothalamus. It supports the axons of hypothalamic secreting neurons rooted in the supraoptic and paraventricular nuclei.

  • Specialized Cells of the Anterior Pituitary:

    • Somatotropes: Secrete Growth Hormone (GH).
    • Corticotropes: Secrete Adrenocorticotropin (ACTH).
    • Thyrotropes: Secrete Thyroid-Stimulating Hormone (TSH).
    • Gonadotropes: Secrete Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH).
    • Lactotropes: Secrete Prolactin.
    • Note: One cell type usually forms one hormone; however, the same cell type (gonadotropes) secretes both LH and FSH.

  • Hypothalamic Control of the Anterior Pituitary:

    • Mechanism: Hypothalamic hormones are secreted into the median eminence, enter capillaries, travel via hypophyseal-portal vessels, and act on anterior pituitary cells.
    • Trophic Hormones:
      • Corticotropin-releasing hormone (CRH): Stimulates ACTH.
      • Thyrotropin-releasing hormone (TRH): Stimulates TSH and Prolactin.
      • Growth hormone-releasing hormone (GHRH): Stimulates GH.
      • Somatostatin: Inhibits GH and other hormones.
      • Gonadotropin-releasing hormone (GnRH): Stimulates LH and FSH.
      • Prolactin-releasing hormone (PRH): Stimulates Prolactin (PRL).
      • Prolactin-inhibiting hormone (PIH/Dopamine): Inhibits Prolactin.

Growth Hormone (GH) Physiology

  • Biological Features:

    • A single polypeptide chain consisting of 200200 amino acids.
    • Molecular weight of approximately 22,00022,000.
    • Contains 22 disulfide bridges.
    • Synthesized as a prehormone and stored in granules.

  • Regulation of Secretion:

    • Stimulants: GHRH, strenuous exercise, and the first few hours of deep sleep.
    • Inhibitors: Somatostatin (Growth Hormone Inhibitory Hormone/GIH), and Somatomedin (negative feedback).
    • Age Variation: Secretion peaks during puberty and declines during adult years and senescence.

  • Metabolic and Physiological Effects:

    • General Action: Unlike other trophic hormones, GH affects almost all tissues by promoting protein formation, cell multiplication, and differentiation.
    • Anabolic Effects: Increases amino acid uptake, protein/RNA/DNA synthesis; decreases protein degradation.
    • Metabolism of Adipose Tissue (Ketogenic): Increases lipolysis and fatty acid oxidation, leading to ketone formation.
    • Glucose Metabolism (Diabetogenic): Increases plasma glucose by decreasing uptake and oxidation (insulin resistance). Can overstimulate insulin secretion, potentially leading to "Pituitary Diabetes" or Diabetes Mellitus.
    • Skeletal Growth: Stimulates cartilage and bone growth by increasing protein deposition in chondrocytic and osteogenic cells, increasing cell reproduction, and stimulating osteoblast function.
    • Mediators: Many GH effects are mediated by Somatomedins (IGFs) produced in the liver.

  • Pathological Conditions:

    • Dwarfism: Caused by panhypopituitarism during childhood, resulting in growth inhibition and sexual immaturity.
    • Gigantism: Caused by an acidophilic tumor before adolescence (before epiphyses close); growth can exceed 88 feet.
    • Acromegaly: Caused by excessive GH after adolescence (after epiphyses close); results in enlargement of soft tissues and bones such as the lower jaw.

The Posterior Pituitary Gland (Neurohypophysis)

  • Hormone Production and Storage:

    • Hormones are synthesized in the hypothalamus: ADH in the supraoptic nucleus and Oxytocin in the paraventricular nucleus.
    • Hormones travel down nerve fibers to be stored in terminal nerve endings in the posterior pituitary.
    • Pituicytes: Provide structural support for these terminal fibers.

  • Antidiuretic Hormone (ADH/Vasopressin):

    • Water Retention: Binds to V2 receptors in the distal convoluted tubules and collecting ducts; increases cell membrane permeability to water. Net effect: decreased H2OH_2O excretion/increased urine osmolality.
    • Vascular Tone: Binds to V1 receptors on arteriolar smooth muscle; causes vasoconstriction. Net effect: increased blood pressure.

  • Oxytocin:

    • Lactation: Stimulates myoepithelial cell contraction in the breast to secrete milk upon suckling ("milk let down").
    • Parturition: Contracts the uterus during the birthing process.

Questions & Discussion

  • End of Presentation Content:
    • The session concludes with a summary restating that the hypothalamus-pituitary unit is the dominant endocrine portion.
    • A final slide features a comic dialogue: "Is it oxytocin?! No, it's love!" by Alex Martin.
    • Inquiry: The speaker asks the audience, "Any Questions?"