Relationship Between Transcription Factors and S14 Gene Expression in Response to Thyroid Hormone and Age

In this report, we have examined the effect of aging on thyroid hormone regulated S14 gene expression by comparing levels of the mRNA in the liver of young (6-month) and aged (26-month) rats of various thyroid states. Although levels of mRNA-S14 were stimulated by L-triiodothyronine (T3) in both young and aged animals, net activity of the gene in response to the hormone was reduced approximately 2-fold in the aged rats. Next, we wondered whether the effect of age and T3 on levels of the mRNA correlated with changes in the DNA binding activity of two transcription factors, PS-1 and P1 that increase and decrease, respectively, S14 gene activity. The DNA binding activity of PS-1 correlated closely with both age-related and T3-induced S14 mRNA expression. Whereas the DNA binding activity of P1 was significantly reduced in aged rats, T3 failed to influence the activity of P1. Based on these observations, we postulated that age-related increases in S14 gene expression arise from combined changes in activity of the transcription factors, PS-1 and P1. However, T3 regulated S14 gene activity is more closely related to PS-1.