Rat Endocrinology
Hypothalamus
1. What is the molecular mechanism to release TRH?
TRH refers to the thyrotropin-releasing hormone. This hormone is produced by the hypothalamus. Before the full activity of TRH, some tightly controlled processes occur in the body including the appropriate folding of prohormone to move to the secretary pathway, the processing after translation, and movement of the peptides, which are processed, towards the secretary granules for secretion (Nillni n.p.).
TRH develops from bigger inactive precursor (known as proTRH) as a result of modifications after translation and moved through the controlled secretary pathway. Prohormone convertases (abbreviated as PCs) including PC1/3 and PC2 are involved in the processing of TRH. Some exopeptidases as, for example, carboxyl peptidase E and D are also involved in further processing of intermediate products to eliminate the C-terminal basic amino acids. TRH-gly, which is a precursor for TRH, is amidated at the carboxyl terminus as a result of the activity of the enzyme peptidylglycine α-amidating monooxygenase. TRH is released in the capillaries of the hypophysial-portal system, which are present closely to the TRH neurons. These neurons, which are highly innervated by norepinephrine, have axons that activate TRH secretion. On the other hand, increased level of corticosterone can decrease TRH secretion (Nillni n.p.).
2. What type of neurons (name)?
TRH neurons have an important role in the TRH secretion. TRH neurons are found in the paraventricular nucleus of the hypothalamus (PVN) and certain other areas of the hypothalamus including the anterior hypothalamus, preoptic area, supraoptic, dorsomedial, arcuate, and premmamilary nuclei, as well as prefornical and basolateral hypothalmus (Nillni n.p.). TRH was also found to stimulate dorsal motor nucleus of the vagus (DMV) neurons and stop the activity of nucleus of the solitary tract (NST) neurons. Combination of these activities of neurons and TRH helps in the potent as well as long lasting activity of TRH (Barrett 861).
3. What is the relationship between the neurons and blood vessels?
Researchers have found that neurons develop in an inside out manner, whereas blood vessels develop in the opposite direction from the pial surface towards the ventricular surface. Close coordination of these two growth processes are showing that same signaling molecules are involved (Goethe-Universität, goethe-university-frankfurt.de), thereby bringing the neurons and blood vessels together.
4. How T3 and T4 stimulate the release of TRH? So, its action potential.
T3 refers to triidothyronine and T4 refers to thyroxine. These thyroid hormones result in the release of TRH through a negative regulation (Nillni n.p.). Actually, thyroid stimulating hormone (TSH) is involved in the production of T3 and T4. Pituitary TSH secretion is regulated by negative-feedback mechanism controlled by the circulating levels of free T3 and free T4. Increased levels of free T3 and free T4 can stop the release of TSH, whereas decreased levels of free T3 and free T4 can activate the release of TSH. TSH secretion is also influenced by TRH. It has been found that the release of TRH between the pituitary and hypothalamus activate the release of TSH from the anterior pituitary thyrotropic cells (Ramachandran, Alex, and Chan 186). Therefore, these studies show that the decrease in the level of free T3 and T4 in the body causes an increased release of TRH as hypothalamus senses their decreased levels and releases TRH or vice versa (Reisner 401).
TRH in blood
1. What is the pathway (specific blood vessels)?
After the production of TRH peptide in hypothalamic portion of the brain, it is moved via axon terminals to the median eminence, which is a portion of the hypothalamus, from where it is moved into the capillaries of the hypophysial-portal system to stimulate the production and TSH release from the pituitary gland (Nillni n.p.).
2. How does TRH travel in plasma (mechanism)?
TSH
TSH refers to thyroid stimulating hormone. It is a glycoprotein and is a pituitary hormone that is related to the production of T4 and T3 from thyroid gland. The TSH receptor is mainly present on thyroid follicular cells. Activation of the receptor enhances the production as well as secretion of T3 and T4. T3 and T4, in turn, are involved in increasing the metabolism of almost every part of the body. TSH secretion takes place throughout life, but its secretion increases during the periods of high level of growth and activity in life.
TSH is produced from the pituitary gland as a result of the stimulation by TRH, which is produced in the hypothalamus located in the base of the brain. On the other hand, somatostatin, also produced by hypothalamus, can decrease or inhibit the production of TSH (Timiras 149).
T3 and T4
What does it do?
T3 and T4 are thyroid hormones that are involved in the transcription of important genes by attaching to a family of nuclear receptors in the body. In the body, T4 is initially produced and then converted to a more active form, i.e. T3, which is involved in the regulation of metabolism. T3 influences nearly every physiological process in the body including metabolism, growth and development, heart rate, and temperature. As a result of the affect of T3 on the heart, cardiac output is increased, thereby resulting in an increased systolic blood pressure along with a decreased diastolic blood pressure. It also affects the protein myosin, thereby affecting contractility (Nillni n.p.).
These hormones are important in the sustained protein synthesis as well as metabolic activity in peripheral tissues. These hormones are also important in maintaining thermogenesis. It has been reported that approximately 30% of the resting energy expenditure depends on thyroid hormones, and they are important in facultative thermogenesis in cold exposure (Nillni n.p.).
How does it do it?
Research shows that thyroid hormones affect thermogenesis by influencing the uncoupling proteins referred to as UCP-1, UCP-2 and UCP-3 in the muscle and brown adipose tissue along with the activation of the sympathetic nervous system to increase ATP turnover (Nillni n.p.).
Experiment 4: Determining the Effect of Propylthiouracil on Metabolic Rate
Propylthiouracil (PTU) is used to stop the production of thyroxine in the body (Pieracci, and Moore 523). In the experiment, normal rat was compared with thyroidectomized rat in which thyroid gland was removed and hypophysectomized rat in which pituitary gland was removed.
Results of the experiment showed that the normal rat showed the highest level of basal metabolic rate. This is due to the fact that pituitary gland or thyroid gland was not missing in the normal rat, and the rat showed the normal level of basal metabolic rate that is higher than others. In thyroidectomized rat, T3 and T4 were missing, whereas in hypophysectomized rat, TSH was missing due to the absence of pituitary gland. Thyroid glands in the normal rat helped the rat in stimulating and regulating the release of thyroid hormones, whereas the rats without thyroid gland and pituitary gland were unable to produce thyroxine, thereby leading to decreased metabolic rate. In order to normalize thyroidectomized rat, thyroid hormones (thyroxine) can be injected into the rat.
After injection of thyroxine into the normal rat, its basal metabolic rate increased that was clearly seen as thyroxine affected all the cells in the body. After injection of thyroxine into the thyroidectomized rat, the basal metabolic rate increased as the rat has no natural production of thyroxine, but it was still below the normal rat’s basal metabolic rate after thyroxine injection. Moreover, the injection of thyroxine into the hypophysectomized rat helped in increasing the baseline metabolic rate but it was still below the normal rat with thyroxine injection. This is due to the fact that normal rat also had normal thyroxine production in the body.
After injection of TSH into the normal rat, the baseline metabolic rate was increased as compared to the basal metabolic rate without any injection. This is due to the fact that the rat was already producing thyroxine naturally. Injection of TSH into the thyroidectomized rat did not affect the baseline metabolic rate as the rat had no thyroid gland to stimulate the production of thyroxine. However, injection of TSH into the hypophysectomized rat elevated the basal metabolic rate, but the level was still below that of normal rat with TSH injection.
Finally, in the normal rat, injection of PTU resulted in decreased basal metabolic rate and that level was lower than thyroidectomized rat and hypophysectomized rat. In the thyroidectomized rat, injection of PTU resulted in no effects as the rat had no thyroid gland that could be affected by the drug. Similarly, in the hypophysectomized rat injection of PTU resulted in no effects as the rat had no pituitary gland.
Works Cited
Barrett, K.E., et al. Physiology of the Gastrointestinal Tract. Elsevier Science, 2006. Print.
Goethe-Universität. " How Do Neurons and Blood Vessels “Talk” to Each Other?". Goethe-Universität. 2015. Web. 25 May. 2016 <http://www.britannica.com/EBchecked/topic/299621/Rumi >.
Nillni, Eduardo A. "Regulation of the Hypothalamic Thyrotropin Releasing Hormone (Trh) Neuron by Neuronal and Peripheral Inputs." Frontiers in neuroendocrinology 31.2 (2010): 134-56. Print.
Pieracci, F.M., and E.E. Moore. Denver Health Medical Center Handbook of Surgical Critical Care: The Practice and the Evidence. World Scientific Publishing Company, 2015. Print.
Pocock, G., C.D. Richards, and D. Richards. Human Physiology. OUP Oxford, 2013. Print.
Ramachandran, M., M. Alex, and C. Chan. Intercollegiate Mrcs: An Aid to the Viva Examination. Pastest, 2005. Print.
Reisner, H. Pathology: A Modern Case Study. McGraw-Hill Education, 2014. Print.
Timiras, P.S. Physiological Basis of Aging and Geriatrics, Fourth Edition. CRC Press, 2007. Print.
