Endocrine System - Thyroid and Parathyroid Glands, Adrenal Glands, Pineal Gland, Pancreas, and Other Endocrine Organs

Thyroid Gland

  • Location and Structure:
    • Butterfly-shaped gland in the anterior neck, on the trachea, just inferior to the larynx.
    • Composed of:
      • Isthmus: Median mass connecting two lateral lobes.
      • Follicles: Hollow spheres of epithelial follicular cells that produce thyroglobulin (a glycoprotein).
    • Colloid: Fluid within the follicle lumen containing thyroglobulin plus iodine; precursor to thyroid hormone.
    • Parafollicular cells: Produce calcitonin.

Thyroid Hormone (TH)

  • General Information:
    • The body's major metabolic hormone.
    • Affects virtually every cell in the body by binding to intracellular receptors within the nucleus.
    • Triggers transcription of various metabolic genes.
  • Forms:
    • T4 (Thyroxine): Major form; two tyrosine molecules with four bound iodine atoms.
    • T3 (Triiodothyronine): Two tyrosines with three bound iodine atoms; must be converted from T4 at the tissue level.
    • Both are iodine-containing amine hormones.
  • Effects:
    • Increases basal metabolic rate and heat production (calorigenic effect).
    • Regulates tissue growth and development, critical for normal skeletal, nervous system development, and reproductive capabilities.
    • Maintains blood pressure by increasing adrenergic receptors in blood vessels.

Synthesis of Thyroid Hormone

  • The thyroid gland stores hormones extracellularly in the follicle lumen until triggered by TSH (Thyroid-Stimulating Hormone) to release them.
    1. Thyroglobulin Synthesis: Thyroglobulin is synthesized and discharged into the follicle lumen.
    2. Iodide Trapping: Iodide ions (I-) are actively taken into the cell and released into the lumen.
    3. Iodide Oxidation: Electrons are removed, converting iodide to iodine (I2).
    4. Iodine Attachment to Tyrosine:
      • Mediated by peroxidase enzymes.
      • Monoiodotyrosine (MIT): Formed if one iodine attaches.
      • Diiodotyrosine (DIT): Formed if two iodines attach.
    5. Iodinated Tyrosines Link:
      • One MIT and one DIT link to form T3.
      • Two DITs link to form T4.
    6. Colloid Endocytosis: Follicular cells endocytose the colloid, and the vesicle combines with a lysosome.
    7. Hormone Secretion:
      • Lysosomal enzymes cleave T3 and T4 from thyroglobulin.
      • Hormones are secreted into the bloodstream; mostly T4 is secreted, but T3 is also secreted.
      • T4 is converted to T3 at the tissue level.

Thyroid Hormone (TH) - Transport and Regulation

  • Transport:
    • T4 and T3 are transported by thyroxine-binding globulins (TBGs).
    • T3 is 10 times more active than T4.
    • Peripheral tissues convert T4 to T3 via an enzyme that removes one iodine atom.
  • Regulation:
    • TH release is regulated by negative feedback.
      • Falling TH levels stimulate TSH release.
      • Rising TH levels inhibit TSH release.
    • TSH can be inhibited by GHIH, dopamine, and increased levels of cortisol and iodide.
    • Hypothalamic thyrotropin-releasing hormone (TRH) can overcome negative feedback during pregnancy or exposure to cold, especially in infants.

Clinical - Homeostatic Imbalances of Thyroid Hormone

  • Hyposecretion (Adults):
    • Myxedema: Low metabolic rate, thick/dry skin, puffy eyes, feeling chilled, constipation, edema, mental sluggishness, lethargy.
    • Goiter: May develop due to iodine deficiency, leading to decreased TH levels and increased TSH secretion, causing the thyroid to enlarge as it synthesizes unusable thyroglobulin.
  • Hyposecretion (Early Childhood):
    • Congenital Hypothyroidism: Poor thyroid gland development, pituitary problems, or maternal medications may affect TH production.
      • Symptoms: Weak cry, poor feeding, constipation, prolonged jaundice.
      • Treatment: Lifelong TH replacement is crucial.
  • Hypersecretion:
    • Graves’ Disease: Autoimmune disease where the body makes abnormal antibodies that mimic TSH, stimulating TH release.
      • Symptoms: Elevated metabolic rate, sweating, rapid/irregular heartbeats, nervousness, weight loss despite adequate food intake.
      • Exophthalmos: Protrusion of the eyes due to edematous and fibrous tissue behind the eyes.
    • Treatments: Surgical removal of the thyroid or radioactive iodine to destroy active thyroid cells.

Calcitonin

  • Produced by parafollicular (C) cells in response to high Ca2+Ca^{2+} levels.
  • Antagonist to parathyroid hormone (PTH).
  • Role:
    • Inhibits osteoclast activity, preventing Ca2+Ca^{2+} release from the bone matrix.
    • Stimulates Ca2+Ca^{2+} uptake and incorporation into the bone matrix.
    • No known physiological role in humans at normal levels, effects are only seen at higher-than-normal doses.

Parathyroid Gland

  • Structure and Function:
    • Four to eight tiny yellow-brown glands embedded in the posterior aspect of the thyroid.
    • Contain oxyphil cells (function unclear) and parathyroid cells that secrete parathyroid hormone (PTH).
    • PTH is the most important hormone in Ca2+Ca^{2+} homeostasis.
  • Secretion:
    • Secreted in response to low blood levels of Ca2+Ca^{2+}.
    • Inhibited by rising levels of Ca2+Ca^{2+}.
  • Target Organs:
    • Skeleton, kidneys, and intestine.
  • Functions:
    • Stimulates osteoclasts to digest bone matrix and release Ca2+Ca^{2+} to the blood.
    • Enhances reabsorption of Ca2+Ca^{2+} and secretion of phosphate (PO43−PO_4^{3-}) by the kidneys.
    • Promotes activation of vitamin D by kidneys, which leads to increased absorption of Ca2+Ca^{2+} by intestinal mucosa.

Clinical - Homeostatic Imbalances of Parathyroid Hormone

  • Hyperparathyroidism:
    • Usually due to a parathyroid gland tumor.
      • Results: Calcium leaches from bones, causing them to soften and deform; elevated Ca2+Ca^{2+} depresses the nervous system and contributes to the formation of kidney stones.
      • Osteitis fibrosa cystica: A severe form resulting in easily fractured bones.
  • Hypoparathyroidism:
    • Following gland trauma or removal, can cause hypocalcemia.
      • Results: Tetany, respiratory paralysis, and death.

Adrenal Gland

  • Structure:
    • Paired, pyramid-shaped organs atop the kidneys (suprarenal glands).
    • Two glands in one:
      • Adrenal Cortex: Three layers of glandular tissue that synthesize and secrete different hormones.
      • Adrenal Medulla: Nervous tissue that is part of the sympathetic nervous system.

Adrenal Cortex

  • General Information:
    • Produces over 24 different hormones called corticosteroids (steroid hormones).
    • Steroid hormones are not stored in cells; release rate depends on the synthesis rate.
  • Layers and Hormones Produced:
    • Zona Glomerulosa: Mineralocorticoids.
    • Zona Fasciculata: Glucocorticoids.
    • Zona Reticularis: Gonadocorticoids.

Mineralocorticoids

  • Function:
    • Regulate electrolyte concentrations (primarily Na+Na^+ and K+K^+) in the ECF.
    • Importance of Na+Na^+: Affects ECF volume, blood volume, blood pressure, and levels of other ions (K+K^+, H+H^+, HCO3−HCO_3^-, and Cl−Cl^-).
    • Importance of K+K^+: Sets resting membrane potential of cells.
  • Aldosterone:
    • Most potent mineralocorticoid.
      • Stimulates Na+Na^+ reabsorption by the kidneys, leading to increased blood volume and blood pressure.
      • Stimulates K+K^+ elimination by the kidneys.
  • Regulation of Aldosterone Secretion:
    • Renin-Angiotensin-Aldosterone Mechanism
    • Plasma Concentration of K+K^+.
    • ACTH (Adrenocorticotropic Hormone).
    • Atrial Natriuretic Peptide (ANP).

Mechanisms Controlling Aldosterone Release

  • Renin-Angiotensin-Aldosterone Mechanism:
    • Decreased blood pressure stimulates special cells in kidneys to release renin into the blood.
    • Renin cleaves angiotensinogen, leading to a cascade that converts it to angiotensin II.
    • Angiotensin II stimulates aldosterone release.
  • Plasma Concentration of K+K^+:
    • Increased K+K^+ directly influences zona glomerulosa cells to release aldosterone; low levels inhibit it.
  • ACTH:
    • Can cause small increases of aldosterone during increased stress.
  • Atrial Natriuretic Peptide (ANP):
    • Secreted by the heart in response to high blood pressure; blocks renin and aldosterone secretion to decrease blood pressure.

Clinical - Homeostatic Imbalances of Mineralocorticoids

  • Aldosteronism (Hypersecretion):
    • Usually due to adrenal tumors.
      1. Hypertension and edema due to excessive Na+Na^+.
      2. Excretion of K+K^+, leading to abnormal non responsive neurons and muscle.

Glucocorticoids

  • Function:
    • Influence the metabolism of most cells and help resist stressors.
    • Keep blood glucose levels relatively constant.
    • Maintain blood pressure by increasing the action of vasoconstrictors.
  • Hormones:
    • Cortisol (hydrocortisone): The most significant glucocorticoid in humans.
    • Cortisone.
    • Corticosterone.
  • Regulation of Secretion:
    • Cortisol is released in response to ACTH.
    • ACTH is released in response to corticotropin-releasing hormone (CRH).
    • CRH is released in response to low cortisol levels; increased cortisol levels inhibit ACTH and CRH through negative feedback.
    • Cortisol secretion cycles are governed by patterns of eating and activity, acute stress interrupts this rhythm.

Actions of Glucocorticoids

  • Actions:
    • Cortisol increases blood levels of glucose, fatty acids, and amino acids.
    • Primarily affects gluconeogenesis: The formation of glucose from fats and proteins, encouraging cells to use fatty acids for fuel, saving glucose for the brain.
    • Enhances vasoconstriction, causing a rise in blood pressure to distribute nutrients quickly to cells.
  • Excessive Levels of Glucocorticoids:
    • Depress cartilage and bone formation.
    • Inhibit inflammation by decreasing the release of inflammatory chemicals.
    • Depress the immune system.
    • Disrupt normal cardiovascular, neural, and gastrointestinal functions.

Clinical - Homeostatic Imbalances of Glucocorticoids

  • Hypersecretion (Cushing’s Syndrome/Disease):
    • Depresses cartilage/bone formation and the immune system; inhibits inflammation; disrupts neural, cardiovascular, and gastrointestinal function.
    • Causes: Tumor on the pituitary, lungs, pancreas, kidney, or adrenal cortex; overuse of corticosteroids.
    • Cushingoid signs: “Moon” face and “buffalo hump.”
    • Treatment: Removal of the tumor, discontinuation of drugs.
  • Hyposecretion (Addison’s Disease):
    • Usually involves deficits in both glucocorticoids and mineralocorticoids, decreasing plasma glucose and Na+Na^+ levels.
    • Symptoms: Weight loss, severe dehydration, and hypotension.
    • Treatment: Corticosteroid replacement therapy.
    • Early sign: Characteristic bronzing of the skin due to high levels of ACTH, which triggers melanin production in melanocytes.

Gonadocorticoids

  • Function:
    • Weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens.
      • Examples: Androstenedione and dehydroepiandrosterone (DHEA).
  • May Contribute To:
    • Onset of puberty and appearance of secondary sex characteristics.
    • Sex drive in women.
    • Source of estrogens in postmenopausal women.

Clinical - Homeostatic Imbalances of Gonadocorticoids

  • Hypersecretion (Adrenogenital Syndrome/Masculinization):
    • Not noticeable in adult males (already masculinized with testosterone).
    • Females and prepubertal males:
      • Boys: Reproductive organs mature; secondary sex characteristics emerge early.
      • Females: Beard, masculine pattern of body hair; clitoris resembles a small penis.

Adrenal Medulla

  • Function:
    • Medullary chromaffin cells synthesize catecholamines: epinephrine (80%) and norepinephrine (20%).
  • Effects of Catecholamines:
    • Vasoconstriction.
    • Increased heart rate.
    • Increased blood glucose levels.
    • Blood diverted to the brain, heart, and skeletal muscle.
  • Differences Between Epinephrine and Norepinephrine:
    • Epinephrine: More of a stimulator of metabolic activities (e.g., bronchial dilation, blood flow to skeletal muscles and heart).
    • Norepinephrine: More influence on peripheral vasoconstriction and blood pressure.
  • Responses to Stressors:
    • Brief, unlike adrenal cortical hormones.

Clinical - Homeostatic Imbalances of Adrenal Medulla

  • Hyposecretion:
    • Epinephrine and norepinephrine are not essential for life; therefore, there are no problems associated with hyposecretion.
  • Hypersecretion:
    • Leads to symptoms of uncontrolled sympathetic nervous system activity, such as hyperglycemia, increased metabolic rate, rapid heartbeat, palpitations, hypertension, intense nervousness, and sweating.
    • Can be due to pheochromocytoma, a tumor of medullary chromaffin cells.

Pineal Gland

  • Location:
    • Small gland hanging from the roof of the third ventricle.
  • Function:
    • Pinealocytes secrete melatonin, derived from serotonin.
  • Melatonin May Affect:
    • Timing of sexual maturation and puberty.
    • Day/night cycles.
    • Physiological processes that show rhythmic variations (body temperature, sleep, appetite).
    • Production of antioxidant and detoxification molecules in cells.

Pancreas

  • Structure:
    • Triangular gland located partially behind the stomach with both exocrine and endocrine cells.
    • Acinar cells (exocrine): Produce enzyme-rich juice for digestion.
    • Pancreatic islets (islets of Langerhans) contain endocrine cells.
      • Alpha(α\alpha) cells produce glucagon (hyperglycemic hormone).
      • Beta(β\beta) cells produce insulin (hypoglycemic hormone).

Glucagon

  • Function:
    • Extremely potent hyperglycemic agent, triggered by decreased blood glucose levels, rising amino acid levels, or sympathetic nervous system.
    • Raises blood glucose levels by targeting the liver to:
      • Break down glycogen into glucose (glycogenolysis).
      • Synthesize glucose from lactic acid and other noncarbohydrates (gluconeogenesis).
      • Release glucose into the blood.

Insulin

  • Function:
    • Secreted when blood glucose levels increase; synthesized as proinsulin that is then modified.
    • Lowers blood glucose levels by:
      • Enhancing membrane transport of glucose into fat and muscle cells.
      • Inhibiting the breakdown of glycogen to glucose.
      • Inhibiting the conversion of amino acids or fats to glucose.
  • Additional Information:
    • Not needed for glucose uptake in the liver, kidney, or brain.
    • Plays a role in neuronal development, learning, and memory.
    • Binding to the tyrosine kinase enzyme receptor triggers the cell to increase glucose uptake.
    • Also triggers cells to:
      • Catalyze the oxidation of glucose for ATP production (first priority).
      • Polymerize glucose to form glycogen.
      • Convert glucose to fat (particularly in adipose tissue).
  • Factors Influencing Insulin Release:
    • Elevated blood glucose levels (primary stimulus).
    • Rising blood levels of amino acids and fatty acids.
    • Release of acetylcholine by parasympathetic nerve fibers.
    • Hormones: Glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids.
    • Somatostatin and the sympathetic nervous system inhibit insulin release.

Clinical - Homeostatic Imbalances of Pancreatic Hormones

  • Diabetes Mellitus (DM):
    • Can be due to hyposecretion of insulin (Type 1) or hypoactivity of insulin (Type 2).
      • Polyuria: Huge urine output because glucose acts as an osmotic diuretic.
      • Polydipsia: Excessive thirst due to water loss from polyuria.
      • Polyphagia: Excessive hunger and food consumption because cells cannot take up glucose and are “starving.”
  • Lipidemia and Ketoacidosis:
    • When sugars cannot be used as fuel (in DM), fats are used, causing lipidemia: high levels of fatty acids in the blood.
    • Fatty acid metabolism results in the formation of ketones (ketone bodies).
    • Ketones are acidic, and their build-up in the blood can cause ketoacidosis; also causes ketonuria: ketone bodies in the urine.
    • Untreated ketoacidosis causes hyperpnea, disrupted heart activity and O2O_2 transport, and severe depression of the nervous system which can lead to coma and death.
  • Hyperinsulinism:
    • Excessive insulin secretion, causing hypoglycemia (low blood glucose levels).
    • Symptoms: Anxiety, nervousness, disorientation, unconsciousness, even death.
    • Treatment: Sugar ingestion.

Gonads and Placenta

  • Gonads:
    • Produce the same steroid sex hormones as the adrenal cortex, but in lesser amounts.
    • Ovaries (female gonads) produce estrogens and progesterone.
      • Estrogens: Maturation of reproductive organs and appearance of secondary sexual characteristics.
      • With progesterone: Breast development and cyclic changes in uterine mucosa.
    • Testes (male gonads) produce testosterone.
      • Initiates maturation of male reproductive organs, causes the appearance of male secondary sexual characteristics and sex drive, necessary for normal sperm production, and maintains reproductive organs in a functional state.
  • Placenta (Temporary Endocrine Organ):
    • Secretes estrogens, progesterone, and human chorionic gonadotropin (hCG).

Hormone Secretion by Other Organs

  • Adipose Tissue:
    • Leptin: Appetite control; stimulates increased energy expenditure.
    • Resistin: Insulin antagonist.
    • Adiponectin: Enhances sensitivity to insulin.
  • Gastrointestinal Tract:
    • Enteroendocrine cells secrete:
      • Gastrin: Stimulates the release of HCl.
      • Ghrelin: From the stomach, stimulates food intake.
      • Secretin: Stimulates the liver and pancreas.
      • Cholecystokinin (CCK): Activates the pancreas, gallbladder, and hepatopancreatic sphincter.
      • Incretins: Enhance insulin release and inhibit glucagon.
  • Heart:
    • Atrial natriuretic peptide (ANP): Decreases blood Na+Na^+ concentration, therefore decreasing blood pressure and blood volume.
  • Kidneys:
    • Erythropoietin: Signals the production of red blood cells.
    • Renin: Initiates the renin-angiotensin-aldosterone mechanism.
  • Skeleton:
    • Osteoblasts in bone secrete osteocalcin.
      • Prods pancreas to secrete more insulin, restricts fat storage, improves glucose handling, reduces body fat.
      • Activated by insulin.
      • Low levels are present in type 2 diabetes.
  • Skin:
    • Cholecalciferol: Precursor of vitamin D.
    • Calcitriol: Active form of vitamin D that helps absorb calcium from the intestine; also modulates immunity, decreases inflammation, and may act as an anticancer agent.
  • Thymus:
    • Large in infants and children; shrinks with age.
    • Thymulin, thymopoietins, and thymosins: May be involved in the normal development of T lymphocytes in the immune response (act as paracrines rather than hormones).

Developmental Aspects of the Endocrine System

  • Origin of Hormone-Producing Glands:
    • Arise from all three germ layers.
  • Effects of Environmental Pollutants:
    • Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone function.
    • Sex hormones, thyroid hormone, and glucocorticoids are all vulnerable to the effects of pollutants.
    • Interference with glucocorticoids may help explain high cancer rates in certain areas.
  • Endocrine Function Throughout Life:
    • Most endocrine organs operate well until old age.
    • GH levels decline, accounting for muscle atrophy with age.
    • TH declines, contributing to lower basal metabolic rates.
    • PTH levels remain fairly constant, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH.
    • Glucose tolerance deteriorates with age.
    • Ovaries undergo significant changes and become unresponsive to gonadotropins; problems associated with estrogen deficiency occur.
    • Testosterone also diminishes with age, but the effect is not usually seen until very old age.