Fisiología Endocrina - Hormonas Tiroideas T3 T4 - Síntesis, Secreción (Parte 1/3) (IG:@doctor.paiva)

Introduction to Thyroid Hormones

Overview of the Class

• The class focuses on thyroid hormones, specifically their synthesis and secretion. This is the first part of a three-part series.

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Class Structure

• The session will cover:

• Synthesis and secretion of thyroid hormones (first part).

• Physiological functions of thyroid hormones (second part).

• Regulation of secretion (third part).

Anatomy and Function of the Thyroid Gland

Thyroid Gland Anatomy

• The thyroid gland is located below the larynx and in front of the trachea, weighing approximately 15-20 grams.

• It consists of two functional groups:

• Follicular cells that secrete T3 (triiodothyronine) and T4 (thyroxine).

• Parafollicular cells that release calcitonin.

Hormonal Functions

• The primary function of thyroid hormones is to increase basal metabolism; higher levels lead to increased metabolic rates.

• An excess can elevate metabolism by 60% to 100%, while a deficiency can reduce it by 40% to 50%.

Thyroid Hormone Regulation

Impact on Health Conditions

• Hyperthyroidism results in excessive hormone release, increasing basal metabolism.

• Hypothyroidism leads to decreased hormone levels, resulting in lower metabolic rates.

Feedback Mechanism

• The hypothalamus-pituitary-thyroid axis regulates hormone release:

• Hypothalamus releases TRH (Thyrotropin-Releasing Hormone), stimulating the pituitary gland.

Hormonal Secretion Dynamics

Secretion Ratios

• Approximately 93% of secreted thyroid hormones are T4, with only about 7% being T3 initially released from the gland.

Conversion Process

• Over time, T4 converts into T3 within tissues, which plays a crucial role in metabolic regulation.

Conclusion: Importance of Understanding Thyroid Function

Summary Insights

Understanding Thyroid Follicular Cells and Hormone Synthesis

Structure of Follicular Cells

• The follicular cells are responsible for releasing calcitonin and are organized to form a structure that surrounds a liquid space known as colloid.

• A detailed view shows the arrangement of follicular cells, highlighting their relationship with blood capillaries and interstitial fluid within the follicle.

• The functional unit is identified as the follicular cell, which is cuboidal epithelial in shape, crucial for thyroid function.

Membrane Structures and Functions

• Each follicular cell has two membranes: a basal membrane facing the interstitium and an apical membrane directed towards the colloid.

• The process of thyroid hormone formation begins with iodide uptake from blood into follicular cells via specific transport mechanisms.

Iodide Transport Mechanism

• Iodide is transported through the basal membrane by a sodium-potassium ATPase-dependent transporter called NKCC1, illustrating secondary active transport principles.

• This transport mechanism relies on sodium gradients established by primary active transport (Na+/K+ pump), demonstrating energy dependency.

Role of Pendrin in Iodine Transport

• Once inside, iodide travels to the apical membrane where it exits into the colloid through a protein called pendrin, which exchanges chloride ions for iodide.

Importance of Thyroid Peroxidase

• Thyroid peroxidase (TPO), located at the apical membrane, plays critical roles including oxidizing iodide to iodine—a key step in hormone synthesis.

Synthesis of Thyroglobulin

• Follicular cells synthesize thyroglobulin (Tg), an essential protein containing tyrosine amino acids necessary for hormone production.

• Tg is produced in rough endoplasmic reticulum and packaged in Golgi apparatus before being secreted into colloid.

Organification Process

• In colloid, iodine binds to tyrosine residues on thyroglobulin facilitated by TPO; this process forms monoiodotyrosine (MIT).

Coupling Reactions Leading to Hormones

• MIT can couple with another iodinated tyrosine or itself to form diiodotyrosine (DIT); these reactions lead to T3 (triiodothyronine) and T4 (thyroxine).

Summary of Key Processes by TPO

• TPO catalyzes three main processes: oxidation of iodide, organification with tyrosines forming MIT/DIT, and coupling reactions producing T3/T4 hormones.

Understanding Thyroid Hormones and Their Transport

Role of Thyroglobulin in Hormone Transport

• The thyroglobulin acts as a transport mechanism for thyroid hormones, including T3 (triiodothyronine) and T4 (thyroxine), along with mono-iodotyrosine.

• These hormones are internalized by follicular cells through a process called pinocytosis, where enzymes from lysosomes break down the thyroglobulin to release T3 and T4.

Recycling of Iodide and Tyrosine

• The body efficiently recycles iodide and tyrosine after hormone release; this recycling is crucial for maintaining hormonal balance.

• Iodide is extracted from the breakdown products, allowing it to be reused in hormone synthesis, showcasing the body's intelligent resource management.

Characteristics of Thyroid Hormones

• T3 and T4 are lipophilic hormones that easily enter the bloodstream post-release from follicular cells.

• The primary functions of these hormones include oxidation, organization, and coupling within metabolic processes.

Binding Proteins for Thyroid Hormones

• Approximately 99% of circulating T3 and T4 bind to plasma proteins upon entering the bloodstream.

• Binding Protein Distribution:

• 70% bound to thyroxine-binding globulin

• 20% bound to albumin

• 10% bound to prealbumin

• High affinity between these proteins and thyroid hormones affects their release rates; T4 has a slower release due to higher binding affinity compared to T3.

Release Dynamics of T3 and T4

• The half-life for releasing half of the stored T4 is approximately six days, while T3 releases more rapidly at about once per day due to its lower affinity for binding proteins.

• An analogy illustrates this concept: high affinity (T4 as a stable partner) leads to slower separation compared to low affinity (T3 as an unstable partner).

Cellular Uptake Mechanism

• Both hormones can cross cell membranes easily due to their lipophilicity; they then bind intracellularly with different affinities—T4 having higher affinity than T3.

Latency Period in Metabolic Effects

• After administration of high doses of thyroid hormone (like T4), there’s an initial latency period lasting 2–3 days before significant metabolic changes occur.

• This latency reflects how slowly these hormones act on metabolism despite their prolonged effects lasting weeks or months.

Comparative Action Speed Between Hormones

Understanding Thyroid Hormones and Their Impact on Metabolism

The Latency Period of Thyroid Hormones

• The maximum effect of T3 occurs within two to three days, while T4 takes approximately 10 to 12 days. This difference in latency and action time may be attributed to the affinity for binding with plasma proteins.

• The latency period is influenced by intracellular actions of thyroid hormones, which will be further explored in the next class.

Physiological Functions of Thyroid Hormones

• A brief summary indicates that thyroid hormones are crucial for cellular metabolism; higher levels lead to increased metabolic rates, while lower levels result in decreased metabolism.

Synthesis and Transport Mechanism

• Thyroid hormones are synthesized from iodide, which enters through the basal membrane into the blood capillaries. Iodide then moves across the apical membrane via specific transport mechanisms.

• Iodide undergoes oxidation facilitated by UPT and peroxidase enzymes, combining with tyrosine to form diiodotyrosine (DIT), leading to the production of thyroid hormones.

Characteristics of Thyroid Hormones

• These hormones are lipophilic and travel in blood bound to proteins (99% protein-bound), resulting in a slower release due to their high affinity for these transport proteins.

Importance of Key Enzymes

• The role of thyroperoxidase is emphasized as critical in hormone synthesis processes.