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.