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Thyroid Hormones Flashcards

Hormones of the Thyroid Gland

  • Builds on the hypothalamic-pituitary axis discussed previously.
  • Focus on T3 and T4 hormones.
  • Regulation of thyroid hormone levels is crucial for growth, development, and homeostasis.
  • Actions of thyroid hormones and disorders of thyroid hormone regulation.

Impact of Thyroid Hormone Availability

  • Hypothyroid dog (low thyroid hormone secretion) shows significant differences compared to its state after thyroid hormone supplementation.
  • Hypothyroidism leads to:
    • Obese body habit (not just fat).
    • Lower respiration rate.
    • Lower core body temperature.
    • Reduced activity and alertness.
  • These characteristics are influenced by thyroid hormones.

Hypothalamic-Hypophyseal Tract

  • Neuroendocrine cells in the hypothalamus secrete releasing and inhibitory hormones, influencing the anterior pituitary.
  • Anterior pituitary hormones can directly affect tissues or influence other target tissues to release hormones (multi-step process).
  • Hypothalamus releases hormones influencing the anterior pituitary.
  • Anterior pituitary releases tropic hormones.
    • Tropic hormones: Hormones that cause the release of other hormones from target organs.
  • Target organs (adrenal glands, gonads, thyroid) secrete effector hormones, which have broader effects on the body.
  • Feedback loops regulate the entire cycle.

Anterior Pituitary Hormones

  • Circulation is shared between the hypothalamus and pituitary.
  • Releasing and inhibitory hormones influence the anterior pituitary.
  • Growth hormone is secreted.
  • Other hormones:
    • Prolactin.
    • Luteinizing hormone (LH).
    • Follicle-stimulating hormone (FSH).
    • TSH (thyroid-stimulating hormone): Primary focus, affects the thyroid gland.
    • ACTH (adrenocorticotropic hormone).
  • TSH itself doesn't directly affect metabolism but influences the thyroid gland.
  • Multiple hormones are regulated in this manner.

Hypothalamic Hormones and Their Effects on the Anterior Pituitary

  • Thyrotropin-releasing hormone (TRH) stimulates the release of TSH and prolactin.
  • Corticotrophin-releasing hormone stimulates adrenocorticotropic hormone (ACTH), targeting the adrenal gland.
  • Gonadotropin-releasing hormone.
  • Growth hormone-releasing hormone.
  • Growth hormone-inhibitory hormone.
  • These hypothalamic hormones don't have direct regulatory effects; they influence the creation of other molecules from the anterior pituitary.

Hypothalamus-Pituitary-Thyroid Gland Axis

  • Thyroid gland located around the trachea.

Thyroid Gland

  • Small tissue (about 1 gram in a 15 kg dog) but has significant influence.
  • Two lobes lateral to the trachea.
  • Highly vascularized (receives a large amount of blood flow).
  • Significant lymphatic drainage.
  • Neural innervation.
  • Iodine is crucial for synthesizing thyroxine.
  • Calcitonin regulates calcium metabolism (discussed in another lecture).

Thyroid Tissue Structure

  • Similar structure to salivary glands, mammary tissue, and lung tissue.
  • Follicles: Structures aligned with a single layer of follicular cells surrounding a lumen called the colloid.
  • Follicular cells have extensive mitochondria, Golgi, and endoplasmic reticulum (highly secretory).
  • Microvilli are present on the luminal surface, aiding in the movement of proteins for thyroxine biosynthesis.

Thyroid Hormone Biosynthesis

  • T4 (thyroxine) is the main circulating molecule, but T3 is the active form.
  • T4 is converted to T3 within cells to elicit effects.
  • T3 and T4 are formed from tyrosine residues and iodine.
  • Iodine is absorbed from the intestine and transported into follicular cells via a sodium gradient.
  • Thyroglobulin: A protein within follicular cells containing tyrosine residues that become iodinated.
  • Iodine covalently binds to tyrosine residues within thyroglobulin.
  • The hormone is then cleaved off and stored in the colloid.
  • The number and size of follicular cells change in response to TSH stimulation.
  • Iodine is taken up, thyroglobulin is transported in, and biosynthesis occurs inside the colloid.
  • Iodinated thyroglobulin is transported back; T3 and T4 are cleaved off and transported out.
  • Thyroglobulin is recycled or broken down.
  • Lipophilic hormones are bound to proteins (e.g., thyroid hormone-binding globulin) for transport in circulation.

Detailed Steps of Biosynthesis

  • Iodine is actively transported into follicular cells using ATP.
  • Thyroglobulin (TG) is synthesized.
  • Iodine covalently binds to thyroglobulin at tyrosine residues.
  • Monoiodotyrosine (MIT): One iodine added.
  • Diiodotyrosine (DIT): Two iodines added.
  • Two DITs fuse to form tetraiodothyronine (T4, thyroxine).
  • One DIT and one MIT fuse to form triiodothyronine (T3).
  • Molecules are clipped off the thyroglobulin structure.
  • Thyroglobulin is returned, and MIT and DIT are recycled.
  • T3 and T4 are secreted.

Structures of T3 and T4

  • T4: Formed from two DITs, contains four iodine residues and a modified tyrosine residue.
  • T3: Formed from one MIT and two DITs, contains three iodine molecules and a tyrosine residue.
  • These molecules were previously attached to a larger protein.
  • Thyroglobulin re-enters follicular cells; T3, T4, MIT, and DIT are cleaved off.
  • MIT and DIT are deiodinated, and iodine is reabsorbed.
  • T4 and T3 are released.

Regulation of Thyroid Hormone Release

  • TRH (thyrotropin-releasing hormone) from the hypothalamus affects the anterior pituitary.
  • Anterior pituitary secretes TSH (thyrotropin-stimulating hormone).
  • TSH's only target tissue is the thyroid gland.
  • TSH facilitates synthesis and secretion of T3 and T4.
  • Similar relationships exist in other endocrine axes (e.g., adrenal gland hormones).

Thyroid Stimulating Hormone (TSH)

  • Increases the number and size of follicular cells (hyperplasia and hypertrophy).
  • Goiter: Enlargement of the thyroid tissue due to factors affecting TSH secretion (e.g., tumors, iodine deficiency).
  • Results in increased secretion of T3 and T4 (synthesis and release).
  • Negative feedback: Secretion of T3 and T4 feeds back to the anterior pituitary to regulate TSH secretion.
  • Iodine deficiency can lead to goiter, which is why iodinated salt is used in developed nations.

Actions and Effects of Thyroid Hormones

  • T3 is the active form with very little free T3 in circulation.
  • T4 is more stable (half-life of about a week) compared to T3 (half-life of about a day).
  • Lipophilic hormones move through the plasma membrane.
  • Hormones are typically bound to binding proteins (e.g., albumin, T4-binding prealbumin, T4-binding globulin) for transport.
  • T4 is processed into T3 to influence cellular processes.
  • T3 influences gene expression by binding to promoter regions of genes.

Cellular Effects of T3 and T4

  • Calorigenic effect: Balance of energy availability.
  • Overall growth and development.
  • Normal tissue function.
  • Overall metabolism and viability of cells.
  • T4 is converted to T3 by a deiodinase enzyme.
  • Reverse T3: An inactive form produced when cells don't have enough energy to respond, effectively disabling the signal.
  • Localized mechanism in starvation or liver/kidney disease.

Effects of T3 and Thyroxine on Metabolism

  • Basal metabolic rate is influenced in most tissues (except brain, gonads, and spleen).
  • Increased oxygen consumption and CO2 production indicate increased metabolic activity.
  • Influences the synthesis and degradation of fats, carbohydrates, and proteins.
  • Adults with over- or underactive thyroids show dramatic effects.
  • Growth hormone is necessary for normal growth patterns.
  • Lack of T4 during fetal development results in decreased viability of the fetus.
  • Influences normal gonadal function, estrous cycles, and breeding seasons.
  • Affects water retention and electrolyte movement; hypothyroidism leads to water retention (puffy appearance).
  • Hypothyroid: Decreased protein turnover, positive nitrogen balance.
  • Hyperthyroid: Increased protein turnover and metabolic rate.

Effects on Carbohydrate and Lipid Metabolism

  • Increases glucose absorption in the gut and decreases liver glycogen.
  • Prolonged elevated glucose from hyperthyroidism can potentially result in diabetes mellitus.
  • Stimulates lipolysis and lipid mobilization.
  • Converts cholesterol to bile.
  • Hypothyroidism leads to a buildup of cholesterol, potentially causing arteriosclerosis and cardiac infarct.

Effects on Brain Function and Tissue Function

  • Hypothyroid: Animals are slow and lethargic; not hypervigilant.
  • Hyperthyroid: Animals are reactive and sensitive to everything; cannot sit still.
  • May affect myelin sheaths and vascularity to the central nervous system; damage may not be reversible in young animals.
  • Work efficiency: Hyperthyroid animals tire easily; hypothyroid animals have decreased work capacity.

Cardiovascular Effects

  • Hyperthyroid: Increase in heart rate and blood pressure due to increased metabolic rate and respiration.

Disruptions in Thyroid Function

Hyperthyroidism

  • Increased secretion; more common in cats than dogs.
  • Dogs have a greater rate of hormone metabolism turnover.
  • Animals tend to be skinny due to increased basal metabolism; hypervigilant.
  • Increased appetite (hyperphagia).
  • Elevated heart rate, blood pressure, metabolic rate, and heat production.
  • Low tolerance to temperature change, particularly heat.
  • Treatment involves removal of the thyroid gland and hormone supplementation.

Hypothyroidism

  • Tendency toward obesity; puffiness from water retention.
  • Edema due to mucopolysaccharide accumulation subcutaneously.
  • Often, brittle hair.
  • Lethargy due to decreased metabolic rate.
  • CNS dysregulation due to depletion of myelin sheaths around neurons.
  • Back to the original dog example: Difference in alertness, loss of water retention, and changes in hair condition after thyroxine is returned.

Summary

  • Thyroid controls metabolism, respiration, heart rate, blood pressure, and behaviour.