Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation of 5alpha-reduced progestogens and reduces anxiety-like behavior of middle-aged rats.
Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation of 5alpha-reduced progestogens and reduces anxiety-like behavior of middle-aged rats.
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DOI：
10.1097/fbp.0b013e32833e0a23
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发表时间：
2010-09
影响因子：
1.6
通讯作者：
Paris JJ
中科院分区：
文献类型：
--
作者：
Frye CA;Walf AA;Paris JJ
孕激素影响女性情感行为的机制知之甚少，尽管更年期期间情绪/情感的明显变化与其下降有关。结合马雌激素（CEE），与或不与醋酸甲羟孕酮（MPA），是常见的处方雌激素替代品，但有异质性，这些药物治疗的反应。这些化合物的一个不同之处在于它们能够增强孕酮代谢为其5α-还原产物二氢孕酮（DHP）和5α-甾烷-3 α-醇-20-酮（3α，5 α-THP）。本研究调查是否CEE和MPA的反应可能与代谢孕酮的能力。对维持生殖状态或生殖状态下降的中年雌性大鼠给予溶媒、CEE和/或MPA。测定了对焦虑样（旷场、高架十字迷宫）和社会行为（社会互动试验）以及血浆和海马类固醇水平的影响。我们假设CEE，而不是MPA，会减少焦虑样行为与增加海马代谢的孕酮。CEE，或CEE+MPA，增加了中央条目在开放领域和时间花费在开放的手臂上的十字迷宫，但没有改变社会互动的大鼠保持生殖状态。CEE和（或）CEE+MPA可增加大鼠血浆和（或）海马E2和3α，5 α-THP的含量，而MPA可增加生殖状态下降大鼠海马DHP的含量。简单回归分析表明，海马3α，5 α-THP水平在焦虑样行为的变异中起重要作用。因此，CEE减少中年大鼠焦虑样行为的作用可能部分归因于其提高海马中3α，5 α-THP水平的能力。
The mechanisms by which progestogens influence affective behaviors of females are poorly understood despite clear changes in mood/affect that are associated with their decline during menopause. Conjugated equine estrogens (CEE), with or without medroxyprogesterone acetate (MPA), are commonly-prescribed hormone-replacement, but there is heterogeneity in responses to these pharmacotherapies. One way in which these compounds differ is in their capacity to potentiate metabolism of progesterone to its 5α-reduced products, dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (3α,5α-THP). The present study investigated whether responses to CEE and MPA may be related to the capacity to metabolize progesterone. Middle-aged female rats that had maintained reproductive status, or those that had a decline, were administered vehicle, CEE and/or MPA. Effects on anxiety-like (open field, elevated plus maze) and social behavior (social interaction test), and plasma and hippocampus steroid levels were determined. We hypothesized that CEE, but not MPA, would decrease anxiety-like behavior coincident with increased hippocampal metabolism of progesterone. CEE, or CEE+MPA, increased central entries in the open field and time spent on the open arms of the plus maze, but did not alter social interaction of rats that had maintained reproductive status. CEE and/or CEE+MPA increased E2 and 3α,5α-THP in plasma and/or hippocampus of rats, but MPA increased levels of DHP in the hippocampus of rats with declining reproductive status. Simple regressions demonstrated that hippocampus 3α,5α-THP levels accounted for a significant portion of the variance in anxiety-like behavior. Therefore, effects of CEE to reduce anxiety-like behavior of middle-aged rats may be due, in part, to its capacity to enhance levels of 3α,5α-THP in the hippocampus.