Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review.
Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review.
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DOI：
10.3389/fpsyt.2011.00052
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发表时间：
2011
影响因子：
4.7
通讯作者：
Kippin TE
中科院分区：
文献类型：
--
作者：
Frye CA;Paris JJ;Osborne DM;Campbell JC;Kippin TE
母子互动在出生前就开始了。母亲在妊娠期间的经历在决定中枢神经系统的发育编程方面发挥着重要作用。特别是，妊娠期间的压力会改变后代的发育程序，导致对性别典型和压力敏感的神经发育、神经精神和神经退行性疾病的易感性。然而，这些影响及其潜在机制都尚未得到充分理解。我们的假设是，妊娠期间，四氢孕酮在减轻压力对发育中胎儿的影响方面发挥着特别重要的作用，并且可能在一定程度上介导整个生命周期中明显的变化。具体来说，在发育的关键时期（源于妊娠期间的心理、免疫和/或内分泌应激源）糖皮质激素和孕激素之间的平衡改变可能会永久影响行为、大脑形态和/或神经内分泌敏感过程。 5α-还原孕激素是典型性别、应激敏感和/或疾病相关表型发育编程中不可或缺的一部分。产前应激 (PNS) 可能会改变这些反应，并导致四氢孕酮失调及其对应激轴功能的正常影响。作为神经发育、神经精神和/或神经退行性过程的一个例子，本综述重点关注对滥用药物的反应，这对三七总皂苷和孕激素环境敏感。这篇综述探讨了四氢孕酮可能影响三七总皂苷或受三七总皂苷影响，从而对神经发育、神经精神和/或神经退行性相关过程（例如成瘾）产生影响。
Maternal–offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation) may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress (PNS) may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric, and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to PNS and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, PNS, with consequences for neurodevelopmental-, neuropsychiatric-, and/or neurodegenerative- relevant processes, such as addiction.