Understanding the Relationship Between Serum Thyroid Hormone Levels and Thyroid Hormone Action in Tissues
Start Date
15-4-2021 11:00 AM
End Date
15-4-2021 12:00 PM
Student's Major
Biological Sciences
Student's College
Science, Engineering and Technology
Mentor's Name
David Sharlin
Mentor's Department
Biological Sciences
Mentor's College
Science, Engineering and Technology
Description
One essential component for normal nervous system development is thyroid hormone. Low thyroid hormone during development of the nervous system results in cognitive deficits including low IQ. A growing body of evidence suggests that the amount of circulating thyroid hormone in humans and rodents can be impacted by a number of environmental chemicals. Considering this, our group is investigating the degree to which circulating levels of thyroid hormone must be reduced to observe altered thyroid hormone action in tissues. To test this, we are administering five increasing doses of methimazole (MMI; drug used to block thyroid hormone) to 16-18 week old male mice to induce a step-wise reduction in circulating thyroid hormone. Mice were assigned one of five groups based on MMI dose; 0, 0.002, 0.004, 0.01, 0.05% (weight/volume). Following two weeks of treatment, mouse serum was collected as well as brain, liver, and heart tissues. Serum total T4 levels were determined by enzyme-linked immunosorbent assay (ELISA). We are currently purifying total RNA from liver tissue to assay the well-known thyroid hormone responsive genes in the liver spot14 mRNA levels by qRT-PCR. This work has two goals: (1) Obtain baseline information on the dosing needed to induce a stepwise decrease in serum thyroxine and (2) determine what is minimum decrease needed to observe an adverse outcome as indicated by a change in gene expression in liver, brain, and heart tissues. Our prediction is that a certain level of reduction in thyroid hormone must be reduced to observe significant change in gene expression, and likely mirror the decrease in serum thyroid hormone induced by MMI.
Understanding the Relationship Between Serum Thyroid Hormone Levels and Thyroid Hormone Action in Tissues
One essential component for normal nervous system development is thyroid hormone. Low thyroid hormone during development of the nervous system results in cognitive deficits including low IQ. A growing body of evidence suggests that the amount of circulating thyroid hormone in humans and rodents can be impacted by a number of environmental chemicals. Considering this, our group is investigating the degree to which circulating levels of thyroid hormone must be reduced to observe altered thyroid hormone action in tissues. To test this, we are administering five increasing doses of methimazole (MMI; drug used to block thyroid hormone) to 16-18 week old male mice to induce a step-wise reduction in circulating thyroid hormone. Mice were assigned one of five groups based on MMI dose; 0, 0.002, 0.004, 0.01, 0.05% (weight/volume). Following two weeks of treatment, mouse serum was collected as well as brain, liver, and heart tissues. Serum total T4 levels were determined by enzyme-linked immunosorbent assay (ELISA). We are currently purifying total RNA from liver tissue to assay the well-known thyroid hormone responsive genes in the liver spot14 mRNA levels by qRT-PCR. This work has two goals: (1) Obtain baseline information on the dosing needed to induce a stepwise decrease in serum thyroxine and (2) determine what is minimum decrease needed to observe an adverse outcome as indicated by a change in gene expression in liver, brain, and heart tissues. Our prediction is that a certain level of reduction in thyroid hormone must be reduced to observe significant change in gene expression, and likely mirror the decrease in serum thyroid hormone induced by MMI.
