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  • KPT-276 Progesterone s metabolite THP may also


    Progesterone\'s metabolite, 3α,5α-THP, may also be mediating burying and freezing responses. Results show female Long–Evans rats in behavioral estrous have higher P4 levels in serum, KPT-276 and hippocampus compared to diestrous female Long–Evans rats. Additionally, ovx female Long–Evans rat administered P4 at 4 mg/kg have higher P4 levels in serum, cortex and hippocampus compared to ovx females administered vehicle (Walf et al., 2006). Levels of 3α,5α-THP in plasma, cortex and hippocampus are high when P4 levels are also high, either in behavioral estrous or by subcutaneous injection of P4 (Frye et al., 2000, Walf et al., 2006). These levels have been shown to coincide with reductions in anxiety behaviors (Frye et al., 2000). Results indicate high levels of 3α,5α-THP coincide with reductions in impulsive burying and fear responding. High levels of progestogens (P4 and/or 3α,5α-THP) may mediate burying behavior and/or avoidant behavior as a result of exposure to novel and/or contextually aversive stimuli. Furthermore, E2 alone can enhance 3α,5α-THP biosynthesis, which may contribute to progestogen and/or estrogen\'s effects to mediate impulsivity, anxiety, and/or fear KPT-276 responding (Cheng and Karavolas, 1973, Pluchino et al., 2006, Vongher and Frye, 1999). When P4 is high, performance on tasks that involve the frontal lobe is improved (Solis-Ortiz et al., 2004). The frontal lobe has been implicated in sustained attention, which can include recognition, alertness and working memory (Bearden et al., 2004, Posner and Raichle, 1994, Riccio et al., 2001). Progestogens may improve attention and memory, and influence impulsive and avoidant behaviors. While progestogens may produce positive behavioral effects, physiological effects need to be considered when exploring treatment options. P4 can attenuate trophic effects of E2 on the uterus, which in turn reduce the risk for uterine cancer (Beresford et al., 1997). However, high levels of P4 can produce negative effects as well, such as increasing risk for breast cancer, blood clots, stroke, and heart attack (Thomas et al., 2003). P4 has been implicated as an agonist of blood platelets, which can contribute to cardiovascular complications associated with P4 treatments by increasing coagulation and clotting (Blackmore, 2008). Further investigation is needed to parse out P4\'s beneficial and harmful effects to better understand risks associated with treatments in clinical populations. Thus, progesterone may improve anxiety, impulsivity, and/or fear behaviors through actions by estrogen and/or 3α,5α-THP. These possibilities need to be further explored to determine possible outcomes of hormonal treatments in clinical populations.