Prenatal androgen treatment impairs the suprachiasmatic nucleus arginine-vasopressin to kisspeptin neuron circuit in female mice.
Prenatal androgen treatment impairs the suprachiasmatic nucleus arginine-vasopressin to kisspeptin neuron circuit in female mice.
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DOI：
10.3389/fendo.2022.951344
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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多囊卵巢综合征（PCOS）与雄激素和促黄体生成激素（LH）分泌升高以及少排卵/无排卵相关。有证据表明，雄激素水平升高会损害性类固醇激素对LH脉冲分泌的反馈调节。多囊卵巢综合征（PCOS）的高雄激素血症也可能扰乱排卵前LH激增。然而，这种情况可能发生的机制尚未完全了解。Kisspeptin（KISS 1）神经元的第三脑室（RP3V）的头端室周区传达激素的线索，促性腺激素释放激素（GnRH）神经元。在啮齿类动物中，排卵前激增是由这些激素线索和来自视交叉上核（SCN）的中央昼夜节律钟的同步定时信号触发的。定时信号被传递到GnRH神经元，部分是通过从SCN精氨酸加压素（AVP）神经元到RP3VKISS 1神经元的投射。由于啮齿动物SCN细胞表达雄激素受体（AR），我们假设这些电路在PCOS小鼠模型中受到升高的雄激素的损害。在产前雄激素治疗（PNA）的雌性小鼠，SCN Ar的表达显着增加相比，发现在产前车辆治疗的小鼠。在表达Ar的Avp阳性SCN细胞的数量中观察到类似的趋势。在RP3V中，kisspeptin神经元的数量被保留。然而，顺行追踪显示，减少SCNAVP神经元投射到RP3V和RP3VKISS 1神经元与SCNAVP纤维密切贴壁的比例显着降低。另一方面，功能评估表明，RP3VKISS 1神经元对AVP的反应在PNA小鼠中得以维持。这些发现表明PNA改变了一些调节排卵前峰的神经回路。这些损伤可能导致PCOS模型PNA小鼠排卵功能障碍。
Polycystic ovary syndrome (PCOS) is associated with elevated androgen and luteinizing hormone (LH) secretion and with oligo/anovulation. Evidence indicates that elevated androgens impair sex steroid hormone feedback regulation of pulsatile LH secretion. Hyperandrogenemia in PCOS may also disrupt the preovulatory LH surge. The mechanisms through which this might occur, however, are not fully understood. Kisspeptin (KISS1) neurons of the rostral periventricular area of the third ventricle (RP3V) convey hormonal cues to gonadotropin-releasing hormone (GnRH) neurons. In rodents, the preovulatory surge is triggered by these hormonal cues and coincident timing signals from the central circadian clock in the suprachiasmatic nucleus (SCN). Timing signals are relayed to GnRH neurons, in part, via projections from SCN arginine-vasopressin (AVP) neurons to RP3VKISS1 neurons. Because rodent SCN cells express androgen receptors (AR), we hypothesized that these circuits are impaired by elevated androgens in a mouse model of PCOS. In prenatally androgen-treated (PNA) female mice, SCN Ar expression was significantly increased compared to that found in prenatally vehicle-treated mice. A similar trend was seen in the number of Avp-positive SCN cells expressing Ar. In the RP3V, the number of kisspeptin neurons was preserved. Anterograde tract-tracing, however, revealed reduced SCNAVP neuron projections to the RP3V and a significantly lower proportion of RP3VKISS1 neurons with close appositions from SCNAVP fibers. Functional assessments showed, on the other hand, that RP3VKISS1 neuron responses to AVP were maintained in PNA mice. These findings indicate that PNA changes some of the neural circuits that regulate the preovulatory surge. These impairments might contribute to ovulatory dysfunction in PNA mice modeling PCOS.
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影响因子：
6.1
作者：
Fauser, BCJM;Chang, J;Lobo, R
通讯作者：
Lobo, R
DOI：
10.1371/journal.pctr.0020007
发表时间：
2007-02-09
期刊：
PLoS clinical trials
影响因子：
--
作者：
Danilenko, Konstantin V;Samoilova, Elena A
通讯作者：
Samoilova, Elena A
影响因子：
81.5
作者：
Azziz, Ricardo;Carmina, Enrico;Yildiz, Bulent O.
通讯作者：
Yildiz, Bulent O.
影响因子：
4.8
作者：
Christian, Catherine A.;Moenter, Suzanne M.
通讯作者：
Moenter, Suzanne M.
DOI：
10.1073/pnas.1713897114
发表时间：
2017-11-21
影响因子：
11.1
作者：
Clarkson, Jenny;Han, Su Young;Herbison, Allan E.
通讯作者：
Herbison, Allan E.