P-64 Decreased p44/42 MAPK phosphorylation in gender- or hormone-related but not during age-related adrenal gland growth in mice

Abstract

Postnatal growth of the mouse adrenal gland shows a characteristic gender-dependent pattern, resulting in an almost two-fold higher adrenal weight in 11-week-old female versus male mice. We demonstrated that the higher weight of the adrenal glands in female mice is due to a significantly (p<0.05) increased growth rate in female mice and a shorter growth phase of the adrenal glands in male mice (p<0.05). To address the signaling mechanisms underlying these differential growth patterns, we evaluated the phosphorylation levels of p44/42 and p38 MAPK. In female mice, age dependent reductions of p38 MAPK phosphorylation were found between week 3 and week 9 (47% reduction; p<0.05). At the age of 11 weeks the p38 MAPK phosphorylation level in female adrenal glands was about 60% lower than in the male counterparts (p<0.01). Similarly the phosphorylation level of p44/42 MAPK was 50% lower in female adrenal glands (p<0.001). Reduced activation of p44/42 MAPK was also observed after growth stimulation of the adrenal glands in male mice after ACTH treatment (-36%; p<0.001) or by expression of a growth hormone transgene (-34%; p<0.001), while p38 MAPK, JNK or PDK1 activation were unaffected. From our findings in three independent mouse models where partial deactivation of p44/42 MAPK was observed under conditions of elevated growth we suggest a function of p44/42 MAPK for adrenal growth and a role of p44/42 MAPK for the integration of different endocrine stimuli.