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Decreased p44/42 Mitogen-Activated Protein Kinase Phosphorylation in Gender- or Hormone-Related But Not during Age-Related Adrenal Gland Growth in Mice

Institute of Molecular Animal Breeding and Biotechnology (M.B., E.W., A.H.), Gene Center, and Division of Endocrine Research (M.B., I.J., F.B.), Department of Medicine Innenstadt, Ludwig-Maximilians-Universität, 80539 Munich, Germany; and Laboratory of Mouse Genetics (M.S., A.H.), Research Unit Genetics and Biometry (D.W., A.H.), Research Institute for the Biology of Farm Animals, 18196 Dummerstorf, Germany

Address all correspondence and requests for reprints to: Dr. Andreas Hoeflich, Laboratory of Mouse Genetics, Research Unit Genetics and Biometry, Research Institute for the Biology of Farm Animals, Wilhelm Stahl Allee 2, 18196 Dummerstorf, Germany. E-mail: hoeflich{at}fbn-dummerstorf.de.

Postnatal growth of the mouse adrenal gland shows a characteristic gender-dependent pattern, resulting in an almost 2-fold higher adrenal weight in 11-wk-old female vs. 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 wk 3 and 9 (47% reduction; P < 0.05). At the age of 11 wk, 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 GH transgene (–34%; P < 0.001), whereas p38 MAPK, JNK, or PDK1 activation was 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.