Alterations in cerebellar protein synthesis in propylthiouracil-induced hypothyroid rats

Thyroid hormones play an important role in the regulation of gene expression and cerebellar development in the rat. The drug propylthiouracil was used to disrupt thyroid hormone synthesis. This permitted investigation of gene expression under three different states of hormonal deprivation: early in development (PTU 1), late in development (PTU 2), and continual deprivation (PTU 3). The effects of these deprivations on some aspects of the synthesis of two proteins known to be affected by T3, apolipoprotein E (apo E) and transferrin (T1), were investigated. Thyroid hormone's permissive role on growth and development, morphological features as well as body and organ weights were analyzed and found to be significantly reduced in the hypothyroid state. The development of cerebellar cortical strata and cellular morphology was altered by prenatal, as well as postnatal PTU administration. To establish cerebellar synthesis of apo E and T1, total RNA was extracted, poly A RNA isolated and translated in an in vitro reticulocyte lysate system. The specific proteins were immunoprecipitated and analyzed by SDS-PAGE. To correlate these results with the amounts of mRNA's for apo E and T1, northern hybridization was performed. Both apo E and T1 levels synthesized in vitro with RNA from control animals increased as development proceeded, with apo E produced in greater quantity. While hepatic apo E synthesis increases in the hypothyroid state (presumably as a result of regulation at the transcriptional level), cerebellar apo E translatable mRNA levels were not affected by PTU treatment. Like hepatic T11, cerebellar T1 levels were substantially reduced in the hypothyroid state, as compared to control values. Developmentally, apo E mRNA levels declined, while T1 mRNA levels and T1 synthesized in vitro were parallel in control animals. PTU 1 treated animals, in which free T3 in the circulation increased after PN day 20, demonstrated increases in both apo E and T1 mRNA levels at the same time point. It appears that the regulation of apo E and T1 mRNA levels differ from each other within the cerebellum and may be regulated differently from those of the liver. The increase in in vitro protein synthesis and mRNA levels in PTU 1 treated animals may be a result of developmental recovery, rather than specific T3 mediated gene regulation.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Molecular Biology

Grantor

Texas Woman's University

Year dc:date.issued

1991

Author dc:creator

• Jaworski, Diane

• Thyroid Hormones
• Thyroid Hormone Synthesis
• Gene Expression
• Hormonal Deprivation

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/11274/14774

OAI identifier oai:identifier

oai:twu-ir.tdl.org:11274/14774