Growth hormone induced nuclear translocation of stat3 decreases
with age: modulation by moderate caloric restriction.
Xu, Xiaowei, and William E. Sonntag.
Department of Physiology and Pharmacology, Bowman Gray School of
Medicine of Wake Forest University, Winston-Salem, North Carolina
APStracts 3:0140E, 1996.
Growth hormone induced phosphorylation of JAK2 kinase and the growth
hormone receptor (GHR) in liver as well as expression of IGF-1 mRNA
decrease with age and are reversed by moderate caloric restriction.
In this study, basal levels of JAK2 kinase, Stat3 and MAP kinase as
well as growth hormone induced nuclear translocation of Stat3 and MAP
kinase were compared in hepatic tissues from B6D2 mice to assess the
specific signaling pathways influenced by age and moderate caloric
restriction. Although no age-related differences were observed in
basal JAK2, Stat3 and MAP kinase in ad libitum fed animals, levels of
JAK2 were slightly diminished at 7 months of age in caloric
restricted mice and levels were two-fold greater than ad libitum fed
mice at 36 months (p<0.05). In response to 4 nM growth hormone,
nuclear translocation of Stat3 was more than three-fold greater in 7
month compared to 36 month ad libitum fed mice (p<0.05). The
age-related decline in Stat3 activation was not observed in moderate
caloric-restricted animals. Growth hormone induced nuclear MAP kinase
was similar among all ad libitum fed age groups. Levels were slightly
higher in moderate caloric-restricted mice, but this latter effect
was not significant. We conclude that growth hormone induced
activation of Stat3 is specifically decreased with age and
contributes to the age-related decline in GHR signal transduction and
IGF-1 gene expression. These effects are reversed by moderate caloric
restriction resulting in enhanced tissue response to growth hormone
and increased IGF-1 secretion.
Received 13 March 1996; accepted in final form 28 June 1996.
APS Manuscript Number E122-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996