Glucocorticoids, stress, and fertility.
Glucocorticoids, stress, and fertility.
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发表时间：
2010-06
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通讯作者：
Shannon D. Whirledge;J. Cidlowski
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作者：
Shannon D. Whirledge;J. Cidlowski
下丘脑-垂体-肾上腺轴的改变和循环中糖皮质激素水平的相关变化是生物体对应激挑战反应的关键组成部分。糖皮质激素水平的增加促进糖异生、氨基酸的动员和脂肪分解的刺激，以维持葡萄糖的循环水平，这是产生应激反应所必需的。除了多种组织的生理和功能发生深刻变化外，应激和糖皮质激素升高也可以抑制生殖，这是自我生存的逻辑效应。正常的性腺功能需要精确的糖皮质激素水平；平衡被破坏的地方，生育能力也会被破坏。糖皮质激素在下丘脑-垂体-性腺轴多个层面影响性腺功能：1)下丘脑（减少促性腺激素释放激素[GnRH]的合成和释放）；2)垂体（抑制促黄体生成素[LH]和促卵泡激素[FSH]的合成和释放）；3)睾丸/卵巢（直接调节甾体生成和/或配子发生）。此外，母亲暴露于产前应激或外源性糖皮质激素可导致后代下丘脑-垂体-肾上腺功能和应激相关行为的永久性改变。糖皮质激素对大脑正常发育的许多方面都至关重要，但胎儿暴露于过量的糖皮质激素会导致神经内分泌功能的终身影响。本文综述了糖皮质激素抑制生殖功能的分子机制以及这些作用发生的解剖部位。
Modifications of the hypothalamo-pituitary-adrenal axis and associated changes in circulating levels of glucocorticoids form a key component of the response of an organism to stressful challenges. Increased levels of glucocorticoids promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition to profound changes in the physiology and function of multiple tissues, stress and elevated glucocorticoids can also inhibit reproduction, a logical effect for the survival of self. Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility. Glucocorticoids affect gonadal function at multiple levels in hypothalamo-pituitary-gonadal axis: 1) the hypothalamus (to decrease the synthesis and release of gonadotropin-releasing hormone [GnRH]); 2) the pituitary gland (to inhibit the synthesis and release of luteinizing hormone [LH] and follicle stimulating hormone [FSH]); 3) the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly). Furthermore, maternal exposure to prenatal stress or exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal function and stress-related behaviors in offspring. Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. This review focuses on the molecular mechanisms believed to mediate glucocorticoid inhibition of reproductive functions and the anatomical sites at which these effects take place.