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Department of Molecular Medicine, Karolinska Institute, Karolinska Hospital (P.T.-E., A.F.-M., G.N.), 171 76 Stockholm; and the Department of Biochemistry and Biotechnology, Royal Institute of Technology (J.O., J.L.), 100 44 Stockholm, Sweden
Address all correspondence and requests for reprints to: Dr. Petra Tollet-Egnell, Department of Molecular Medicine, Karolinska Institute, CMM L8:01, Karolinska Hospital, 171 76 Stockholm, Sweden. E-mail: petra.tollet.egnell{at}molmed.ki.se
It has been suggested that aging or at least some of its symptoms are
related to a physiological decline in GH levels with age. This study
was performed to elucidate age-related changes in GH-dependent effects
at the level of gene expression. Through the application of
complementary DNA representational difference analysis (RDA) we have
identified gene products that are reduced during aging in rat liver.
The expression of these genes was restored upon GH treatment. Results
from reverse Northern and ribonuclease protection analysis confirmed
that the RDA products were truly differentially expressed. In addition
to well characterized GH-regulated genes, including CYP2C12, CYP2C13,
and
2u-globulin, we demonstrate the differential
expression of at least 11 genes previously not known to be under GH
control. Several hepatic transcripts encoding enzymes and receptors
involved in the metabolism of protein, carbohydrates, and lipids were
identified. Other RDA products consisted of transcripts encoding
proteins involved in ATP synthesis, detoxification of reactive oxygen
species, or immune responses. This list of GH-regulated genes in the
old rat may shed further light on the action and mechanism behind the
positive effects of GH on, for example, body composition and the immune
system that have been observed in different animal and human studies.
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