Photoperiod-induced changes in hypothalamic de novo DNA methyltransferase expression are independent of triiodothyronine in female Siberian hamsters (Phodopus sungorus).

Many temperate zone animals engage in seasonal reproductive physiology and behavior as a strategy to maximise the propagation of the species. The hypothalamus integrates environmental cues and hormonal signalling to optimize the timing of reproduction. Recent work has revealed that epigenetic modifications, such as DNA methylation, vary across seasonal reproductive states. Multiple hormones act in the hypothalamus to permit or inhibit reproductive physiology, and the increase in thyroid hormone triiodothyronine (T3) has been implicated in the initiation of breeding in many species. The objective of this study was to examine the effect of T3 on the photoperiod-dependent regulation of reproductive physiology and hypothalamic DNA methyltransferase enzyme expression in female Siberian hamsters (Phodopus sungorus). We tested the hypothesis that T3 in short days (SD) would stimulate hypothalamic Rfrp3 and de novo DNA methyltransferase (Dnmt) expression in female Siberian hamsters. 10 weeks of SD lengths induced a decrease in body and uterine mass. Hamsters maintained in SD were found to express lower levels of GnRH, Rfrp3, Dnmt3a and Dnmt3b. Two weeks of daily T3 injections did not affect body mass, uterine mass, Gnrh, Rfrp3, Dnmt3a or Dnmt3b expression in neuroendocrine tissues. SD significantly lowered Tshß mRNA expression and T3 reduced Tshß in LD hamsters. Our data indicate sex-dependent effects of T3 for the neuroendocrine regulation of seasonal reproduction in hamsters.

Environmental and hormonal regulation of epigenetic enzymes in the hypothalamus.

Neuroendocrine structures integrate a vast range of external cues and internal signals that, in turn, result in adaptive physiological responses. Emerging data indicate that light, social cues, stress and energy balance stimulate relatively short- and long-term genomic modifications in discrete neuroendocrine structures, which are mediated by epigenetic mechanisms. Moreover, environmentally-induced fluctuations in the synthesis of local hypothalamic and circulating hormones provide an internal signal that contributes to the extensive neuroendocrine genomic plasticity. This review examines the impact of environmental stimuli and endogenous hormonal signals on the regulation of epigenetic enzymes in key neuroendocrine structures. The data discussed are predominantly derived from studies in the neuroendocrine control of seasonal reproduction and the impact of social stress in rodent models. The perspective presented considers the role of oestrogen and glucocorticoids as the primary catalysts for inducing epigenetic modifications (eg, DNA methylation) in specific neuroendocrine structures. Oestrogen and glucocorticoid actions suggest: (i) a preferential action for specific epigenetic enzymes and (ii) nucleus- and cell-specific modifications. Untangling the complex web of hormonal regulation of methylation and acetylation will enhance our understanding of short- and long-term changes in epigenetic enzymes that generate adaptive and pathological neuroendocrine responses.