Poster Presentation The International Congress of Neuroendocrinology 2014

Androgen can affect photic response of the Suprachiasmatic nucleus via actions on neural androgen receptors in male mice (#180)

Lindsay A Coome , Ashlyn Swift-Gallant , D Ashley Monks

Testosterone plays a powerful role in determining male-typical behaviours, yet we have limited knowledge of how androgen receptors (ARs) influence neural function. The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian (daily) clock that is critical in the temporal organization of circadian activity. Light entrains (synchronizes) circadian rhythms by modulating neural activity of the SCN, and several lines of evidence suggest androgens can alter these responses. Using transgenic mice that over-express ARs only in neurons, the current study investigated the influence of neural AR on the function of the SCN by measuring FOS immunoreactivity after a phase-shifting light pulse. Mutant mice were compared to wild-type siblings and mice of both genotypes were assigned to one of three hormone conditions. Gonadally intact male mice were compared to castrated males treated with dihydrotestosterone, and castrated males treated with vehicle. To test neural activation following exposure to light, animals were exposed to a 30-min light pulse (800 lux) between ZT13.5-14 and then sacrificed after a 60 minute interval. Control animals were not exposed to light. An interaction was observed between androgen status and light condition such that higher levels of circulating androgens were associated with a lesser response to light. Genotype was also found to affect the FOS response to light such that AR overexpressing mice demonstrated a smaller increase in FOS immunoreactivity in response to a light pulse than did wildtypes, indicating that neural AR can modulate the function of the SCN. Together, this culminated in mutant males treated with dihydrotestosterone demonstrating no significant increase in FOS after exposure to light. The effect of genotype observed likely cannot be explained by a reduction in cell number, differences in soma size, or total SCN volume, as no differences were found between mutant and wildtype animals on these measures. However, dihydrotestosterone treatment was found to have an effect on total nucleus size, regardless of genotype. The current study supports a role for neural AR in regulating circadian function.