Doctoral Dissertations

Date of Award

8-1985

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biomedical Sciences

Major Professor

Francis T. Kenney

Committee Members

Howard I. Adler, Salil K. Niyogi, Lee R. Shugart, Elliot K. Volkin

Abstract

Expression In the rat liver of a number of genes (e.g., tyrosine aminotransferase (TAT), phosphoenolpyruvate carboxykinase (PEPCK) is limited but detectable prior to birth, activated in the perinatal period, and hormonally induced in adult liver. The principal objective of this research has been to answer the question: is expression of genes which meet these criteria sensitive to hormonal stimulation prior to developmental activation to the adult level of expression? This aspect of the molecular events involved in hepatic differentiation was investigated using cloned complementary DNAs (cDNAs) cognate to five developmentally regulated messenger RNAs (mRNAs) in rat liver. The cDNAs correspond to genes for TAT, PEPCK, and three as yet unidentified genes, designated gene 33, gene 35 and gene 38. Northern blot and dot hybridization analyses were used to directly measure changes in the level of each of these mRNAs after hormonal stimulation in both adult and fetal liver.

In adult liver, the levels of four of these mRNAs (TAT, PEPCK, gene 33 and gene 35) were increased by hydrocortisone, adenosine 3':5'- monophosphate (cAMP) and insulin. Gene 38 mRNA was increased by hydrocortisone, decreased by insulin and not changed by cAMP. In fetal liver, the level of gene 33 mRNA was increased by all three effectors. However, TAT and PEPCK mRNAs were increased by cAMP but not hydrocortisone or insulin. Gene 38 mRNA was increased by insulin and decreased by cAMP while the level of gene 35 mRNA was increased by both cAMP and insulin in the fetus.

These results show that steroid- and insulin-mediated inductions, as well as induction by cAMP, are capable of functioning in the fetal liver but some genes are not responsive to the inducing agents. This establishes that responsiveness of specific genes to hormonal effectors is gene-specific. This implies that the determining factor as to whether a gene responds to an inducer in fetal liver is likely to require maturation-dependent modifications in the regulatory region of the gene.

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