Carrasco Rodrigo A, Breen Kellie M
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093-0674, USA.
Endocrinology. 2025 Feb 5;166(3). doi: 10.1210/endocr/bqaf021.
Noradrenergic neurons are a brain network that integrate viscero-sensorial signals to modulate neural and neuroendocrine function. Although it has been known for decades that noradrenergic neural circuits influence neuroendocrine and reproductive function, the cellular and molecular players involved remain largely unknown. The objective of this review is to summarize past and current knowledge regarding the influence of brainstem noradrenergic systems on GnRH and gonadotrophin secretion. The main noradrenergic cell groups A1, A2, and A6, known as the ventrolateral medulla, nucleus of the solitary tract, and locus coeruleus, respectively, are involved in the control of reproductive neuroendocrine secretion. Current evidence suggests that brainstem noradrenergic circuits promote the generation and maintenance of the LH surge in both spontaneous (rats, sheep) and induced (rabbit, ferret) ovulators. In contrast, recent studies have established that LH pulsatile secretion is suppressed by specific activation of brainstem noradrenergic cell groups. The duality of the GnRH/LH response to noradrenaline reflects the inherent complexity of hindbrain noradrenaline neurons, which are responsive to stressors and gonadal steroids (ie, estradiol) and coexpress a variety of neurotransmitters and neuropeptides. Therefore, elucidating the organization and functionality of brainstem noradrenergic systems will provide targets for controlling reproduction and understanding the interconnection with stress.
去甲肾上腺素能神经元是一个整合内脏感觉信号以调节神经和神经内分泌功能的脑网络。尽管数十年来人们已经知道去甲肾上腺素能神经回路会影响神经内分泌和生殖功能，但其中涉及的细胞和分子因素在很大程度上仍不清楚。本综述的目的是总结关于脑干去甲肾上腺素能系统对促性腺激素释放激素（GnRH）和促性腺激素分泌影响的过去和当前知识。主要的去甲肾上腺素能细胞群A1、A2和A6，分别被称为腹外侧髓质、孤束核和蓝斑，参与生殖神经内分泌分泌的控制。目前的证据表明，脑干去甲肾上腺素能回路在自发排卵者（大鼠、绵羊）和诱导排卵者（兔子、雪貂）中都促进促黄体生成素（LH）高峰的产生和维持。相比之下，最近的研究表明，脑干去甲肾上腺素能细胞群的特异性激活会抑制LH的脉冲式分泌。GnRH/LH对去甲肾上腺素反应的双重性反映了后脑去甲肾上腺素能神经元固有的复杂性，这些神经元对压力源和性腺类固醇（即雌二醇）有反应，并共表达多种神经递质和神经肽。因此，阐明脑干去甲肾上腺素能系统的组织和功能将为控制生殖以及理解其与压力的相互联系提供靶点。
