Find in Library

Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor (<i>Ptgfr</i>) has no known relationship with biological rhythms. Here, we first measured the locomotor period lengths of <i>Ptgfr-KO</i> (B6.129-<i>Ptgfr^tm1Sna</i>) mice and found that they were longer under constant dark conditions (DD) than those of wild-type (C57BL/6J) mice. We then investigated the clock gene patterns within the suprachiasmatic nucleus in <i>Ptgfr-KO</i> mice under DD and observed a decrease in the expression of the clock gene cryptochrome 1 (<i>Cry1</i>), which is related to the circadian cycle. Moreover, the expression of <i>Cry1</i>, <i>Cry2</i>, and <i>Period2</i> (<i>Per2</i>) mRNA were significantly altered in the mouse liver in <i>Ptgfr-KO</i> mice under DD. In the wild-type mouse, the plasma prostaglandin F_2α (PGF_2α) levels showed a circadian rhythm under a 12 h cycle of light–dark conditions. In addition, in vitro experiments showed that the addition of PTGFR agonists altered the amplitude of <i>Per2</i>::luc activity, and this alteration differed with the timing of the agonist addition. These results lead us to hypothesize that the plasma rhythm of PGF_2α is important for driving clock genes, thus suggesting the involvement of PGF_2α- and <i>Ptgfr</i>-targeting drugs in the biological clock cycle.