| Summary: | <p>Abstract</p> <p>Background</p> <p>We have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (ChrY<sup>C57</sup>) was substituted for that of A/J mice (ChrY<sup>A</sup>), cardiomyocytes from the resulting "chromosome substitution" C57BL/6J-chrY<sup>A </sup>strain were smaller than that of their C57BL/6J counterparts. In reverse, when chrY<sup>A </sup>from A/J mice was substituted for that of chrY<sup>C57</sup>, cardiomyocytes from the resulting A/J-chrY<sup>C57 </sup>strain were larger than in their A/J counterparts. We further used these strains to test whether: 1) the origin of chrY could also be linked to differences in the profile of gene expression in the hearts of adult male mice, and 2) post-pubertal testosterone could play a role in the differential morphologic and/or molecular effects of chrY<sup>C57 </sup>and chrY<sup>A</sup>.</p> <p>Results</p> <p>The increased size of cardiomyocytes from adult male C57BL/6J mice compared to C57BL/6J-chrY<sup>A </sup>resulted from the absence of hypertrophic effects of post-pubertal testosterone on cells from the latter strain. However, gene profiling revealed that the latter effect could not be explained on the basis of an insensitivity of cells from C57BL/6J-chrY<sup>A </sup>to androgens, since even more cardiac genes were affected by post-pubertal testosterone in C57BL/6J-chrY<sup>A </sup>hearts than in C57BL/6J. By testing for interaction between the effects of surgery and strain, we identified 249 "interaction genes" whose expression was affected by post-pubertal testosterone differentially according to the genetic origin of chrY. These interaction genes were found to be enriched within a limited number of signaling pathways, including: 1) <it>p53 signaling</it>, which comprises the interacting genes <it>Ccnd1</it>, <it>Pten </it>and <it>Cdkn1a </it>that are also potential co-regulators of the androgen receptors, and 2) <it>circadian rhythm</it>, which comprises <it>Arntl/Bmal1</it>, which may in turn regulate cell growth via the control of <it>Cdkn1a</it>.</p> <p>Conclusion</p> <p>Although post-pubertal testosterone increased the size of cardiomyocytes from male C56BL/6J mice but not that from their C57BL/6J-chrY<sup>A </sup>counterparts, it affected gene expression in the hearts from both strains. However, several cardiac genes responded to post-pubertal testosterone in a strict strain-selective manner, which provides possible mechanisms explaining how chrY may, in part via interference with androgen regulatory events, be linked to morphologic differences of cardiac cells of adult male mice.</p>
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