Thyroid Hormones Flashcards
What are the functions of thyroid hormone?
Regulates basal metabolic rate: increases body temperature, increases oxygen consumption, stimulates protein carbohydrate and fat metabolism, increases transcription of gene encoding Na/K ATPase, increases production of mitochondria. Required for proper nutritional development (extreme deficiency can result in mental deficiency called cretinism). Signal for metamorphosis in amphibians.
What are thyroid hormones and how are they unique?
Iodinated amino acid derivatives. They are the only iodine-containing compounds in the body. This makes the bodies regulation of thyroid hormones unusual due to the fact that we don’t consume iodine every day. So there’s long-term storage of the hormone precursors sufficient to last for several weeks of normal secretion which buffers against fluctuation in available iodine supply.
Structure of thyroid gland
About 20 grams for normal weight. Derived from embryonic endoderm. 2 lobes joined by a thin isthmus. Sits in the neck.
What are some conditions that increase release of TRH from the hypothalamus?
Cold, trauma, stress.
What is the general pathway and regulation of thyroid hormone release?
TRH (stimulatory) or Somatostatin (inhibitory) is released from the hypothalamus into the anterior pituitary cells. Ant. Pit. Cells release TSH (thyrotropin) which acts on the thyroid. The thyroid release T3 and T4. T3 is the active hormone, but T4 is the one that circulates most in the blood. T3 and T4 negatively regulate TSH release from the hypothalamus.
T3 and T4
T3 is the active hormone, T4 is more abundant in the blood. In peripheral tissues T4 is converted to T3 which can then regulate transcription. T3 binds to a thyroid nuclear receptor (heterodimeric receptor with one of them being RXR and the other the thyroid hormone receptor.
Proterelin
Synthetic derivative of TRH that’s used to test for ant pit function in releasing TSH. Most of the problems with thyroid release stem from regulation of the thyroid itself rather than up in the hypothalamus.
TSH
Once TSH is released, it enters the blood and encounters the thyroid where the TSH receptors are (GPCRs as are most receptors for the an pit hormones but not all, growth hormone is an exception) and works through theGs pathway to stimulate cAMP production. Through PKA phosphorylation, lots of downstream targets areaffected. TSH stimulates all aspects of thyroid hormone synthesis. Simulates the uptake of iodide into thyroid gland. Also stimulates synthesis of the thyroid hormones,which get stored. Also stimulates the reuptake and further metabolism and release of thyroid hormones. So all of the aspects of thyroid synthesis as well as iodide uptake are stimulated.
Effect of ant pit hormones on the cells they stimulate.
alot of ant pit hormones not only stimulate the synthesis of the hormone but they also stimulate the growth and enlargement of the cells. So TSH stimulates thyroid cells to become more active metabolically and enlarge. See notes for feedback inhibition. Feedback inhibition works to prevent too much stimulation and
release of thyroid hormones from the thyroid cells. If theres a iodine deficiency, then too little thyroid will be produced because thyroid hormone requires iodine. So there will be less T3 and T4 and we will lose the negative feedback to the ant pit and hypothalamus. So the thyroid keeps getting stimulated and it grows
and enlarges in an attempt to take up more iodine and make more thyroid hormone (Goiter). Treated by supplying iodine in the diet. Low thyroid hormone can cause mental problems.
Why is there a slow onset of thyroid hormone action?
T4 is the precursor for the active T3 hormone. Slow onset also consistent with transcriptional regulation.
Thyroid tissue
Composed of sacs called follicles. Follicular cells are epithelial cells that synthesize and secrete thyroid hormones thyroxine (T4) and triiodothyronine (T3). Hormone precursors, coupled to thyroglobulin, are stored in jelly-like interior of the follicle, a substance called the colloid. The precursor thyroglobulin becomes iodinated when making it into thyroid.
Activation of the follicles
Inactive: colloid is filled with thyroglobulin that has been iodinated.
Active: stimulated by TSH makes them active as the follicular epithelial cells start taking in the colloidal material the cells swell and expand and actively synthesize the thyroid hormones from the precursors and release it.
Why are anti-thyroid drugs slow to show their effects?
Since the colloid stores thyroid precursor for enough to last several weeks, the large reserve must be depleted before the effects of inhibiting thyroid synthesis are observed.
What are the precursors to thyroid hormones and in general how are they formed to the thyroid hormones?
The thyroid hormones are iodinated derivatives of tyrosine. Precursors: monoiodotyrosine (MIT) and diiodotyrosine (DIT). Iodophenyl rings can be added together. As they’re found in the colloid, they’re still attached to thyroglobulin, which has to be proteolyzed to release the individual amino acids. So the thyroid makes these precursors, stores them in the colloid, and then when they’re ready to be used they are proteolyzed from thyroglobulin to release T3 Nd T4, this is energetically expensive.
Thyroglobulin
Glycoprotein (2 subunits). About 115 tyrosines, only 20 are iodinated. Of the 20, most will end up being MIT and DIT, only 2 T4s will be produced and about 0.3 T3s per thyroglobulin monomer. MIT, DIT, T3, and T4 residues are attached to thyroglobulin inside the follicles for storage. Hormones are released after thyroglobulin is endocytosed and proteolyzed, so we make this huge protein, iodinate it, but only get 2 T3 and 0.3 T4. The rest of the protein has to be degraded and deiodinases have to strip off the iodines from MIT and DIT because iodine is precious to the body. So a lot of energy involved. Synthesized in the endoplasmic reticulum, sent to the Golgi, and subsequently to the follicle lumen.
