Session: SAT 389-413-Signaling and Transcriptional Control in Endocrine Systems
Poster Board SAT-390
Methods: CD-1 male mice pups were injected with either 5µg of testosterone enanthate or vehicle within 24 hours after birth. After insertions of tattoos for group segregation, the mouse pups were mixed and then given back to lactating mothers to eliminate maternal effects and followed to adult age.
Results: Bi-weekly NMR scanning showed neonatally T injected mice had significantly higher percent lean body mass (LBM) than their litter-mate controls (72.7±1.8% vs 67.5±1.0; p<0.05 at 20w). These pro-myogenic organizational effects were particularly pronounced in the androgen sensitive levator ani whose wet weight was significantly greater in mice given a single pulse of testosterone than in mice given vehicle (206.8±9.9mg vs. 172.1±8.5; p<0.05). Immunoblot analysis showed a significant increase in androgen receptor protein expression in the levator ani muscle of T injected mice than in vehicle-injected mice. Injections of a single testosterone pulse at 20 or 40 days of age had no significant effect on LBM or levator ani mass in adulthood. Using LC/MS, we found that the increase in levator animuscle by a single neonatal T injection was accompanied by significantly increase in genomic DNA methylation (3.4±0.2% vs. 3.7±0.1; p<0.001).
Conclusion: A single pulse of testosterone administered during a specific developmental window in immediate postnatal life results in epigenetic programming of muscle mass and AR expression in adult life and is associated with global changes in DNA methylation. The mechanisms of these epigenetic effects need further investigation.
Nothing to Disclose: HJ, JC, GT, CS, SWC, SB, RJ
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