Triiodothyronine (T3) and Thyroxine (T4) Kristal Bent

What Are They? Triiodothyronine (T3) and Thyroxine (T4) are the two main hormones that are produced by the thyroid gland Thyroid gland→ located at the front of the neck below Adam’s apple (larynx) Butterfly-shaped and consists of two lobes→ on both sides of trachea Thyroid functions to regulate body’s metabolic rate, promote growth and development Also heart and digestive function, muscle control, brain development, and bone maintenance Thyroid is under control of the pituitary gland and Thyroid Stimulating Hormone (TSH)

T4 and T3 are secreted by the body in a ratio of 9:1 What Are They? Triiodothyronine (T3) is the active form of the hormone Thyroxine (T4) is the inactive form of the hormone (prehormone) → must be converted within its target cells into the active form → T3 T4 and T3 are secreted by the body in a ratio of 9:1 Thyroxine (T4) travels through blood attached to carrier proteins (99.96%) → it must be free or unbound to enter target cells→ transformed into active form (T3)

How the brain signals the Thyroid gland The Hypothalamus releases TRH (Thyrotropin releasing hormone) TRH travels down the Hypophyseal Portal System to the Anterior Pituitary gland. - Binding to the endocrine cell receptors, it stimulates the secretion of TSH (Thyroid stimulating Hormone.) - TSH moves into the circulatory system to the thyroid gland, where it then binds to the receptors and synthesis and secretion of Thyroid hormones begin.

Synthesis: occurs in the thyroid itself To make both T3 and and T4→ need iodine in diet! Synthesis: Iodine is bound to tyrosine residues in thyroglobulin molecules→ forms mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) (MIT) + (DIT) = Triiodothyronine (T3) (DIT) + (DIT) = Tetraiodothyronine (Thyroxine) (T4) → tyrosine Potassium iodide (1924) → → → →

Mechanism of synthesis of Thyroid Hormones

Mechanism of Thyroid Hormone T4 carried to target cell bound to its plasma carrier protein (thyroxine-binding globulin or TBG) → dissociates from carrier→ passes through membrane of target cell T4 converted to T3 in cytoplasm (enzymatically) T3 uses binding proteins to enter nucleus 4 5 3 6 *lipophilic hormone → pass through membrane 1 7 2

Mechanism of Thyroid Hormone 4) Hormone receptor complex binds to DNA 5) Binding to DNA stimulates synthesis of new mRNA 6) Newly formed mRNA codes for synthesis of new proteins 7) Proteins produce hormonal effects in target cell 4 5 3 6 1 7 2

This shows normal steroid receptors, NOT thyroid hormone receptors How are the Thyroid Hormone Receptors Different From Normal Steroid Receptors? In contrast to steroid hormone receptors, thyroid hormone receptors bind DNA in the absence of hormone (T3)→ transcriptional repression Hormone binding is associated with a conformational change in the thyroid hormone receptor protein that causes it to function as a transcriptional activator→ protein product synthesis causes desired effect ORANGE receptor proteins would bind to DNA WITHOUT hormone and cause transcriptional repression

Sidenote: A goiter is an enlargement of the thyroid gland Most commonly caused by lack of iodine in diet Grave’s disease: (hyperthyroidism) → too much thyroxine (T4) produced Hashimoto’s disease: (hypothyroidism) → too little thyroxine (T4) produced

Symptoms/Effects? Listed below are other symptoms of too much T3 and T4 in your body (hyperthyroidism): Anxiety Irritability or moodiness Nervousness, hyperactivity Sweating or sensitivity to high temperatures Hand trembling (shaking) Hair loss Missed or light menstrual periods The following is other symptoms of too little T3 and T4 in your body (hypothyroidism): Trouble sleeping Tiredness and fatigue Difficulty concentrating Dry skin and hair Depression Sensitivity to cold temperature Frequent, heavy periods Joint and muscle pain

Sources http://www.endocrineweb.com/conditions/thyroid-nodules/thyroid-gland-controls- bodys-metabolism-how-it-works-symptoms-hyperthyroi https://www.boundless.com/physiology/textbooks/boundless-anatomy-and-physiology- textbook/endocrine-system-16/the-thyroid-gland-156/formation-storage-and-release-of- thyroid-hormones-789-4783/ http://www.mayoclinic.org/diseases-conditions/goiter/symptoms-causes/dxc-20264595 http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/receptors.html

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