Centre for Neurobiochemical Studies in Neuroendocrine Diseases, Laboratory of Neurobiochemistry, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Independencia, Chile.
Front Endocrinol (Lausanne). 2021 Feb 25;12:636600. doi: 10.3389/fendo.2021.636600. eCollection 2021.
The functioning of the ovary is influenced by the autonomic system (sympathetic and cholinergic intraovarian system) which contributes to the regulation of steroid secretion, follicular development, and ovulation. There is no information on the primary signal that activates both systems. The nerve growth factor (NGF) was the first neurotrophic factor found to regulate ovarian noradrenergic neurons and the cholinergic neurons in the central nervous system. The aim of this study was to determine whether NGF is one of the participating neurotrophic factors in the activation of the sympathetic and cholinergic system of the ovary and its role in follicular development during normal or pathological states. The administration of estradiol valerate (a polycystic ovary [PCO] phenotype model) increased norepinephrine (NE) (through an NGF-dependent mechanism) and acetylcholine (ACh) levels. Intraovarian exposure of rats for 28 days to NGF (by means of an osmotic minipump) increased the expression of tyrosine hydroxylase and acetylcholinesterase (AChE, the enzyme that degrades ACh) without affecting enzyme activity but reduced ovarian ACh levels. exposure of the ovary to NGF (100 ng/ml for 3 h) increased both choline acetyl transferase and vesicular ACh transporter expression in the ovary, with no effect in ACh level. NGF led to an anovulatory condition with the appearance of follicular cysts and decreased number of corpora lutea (corresponding to noradrenergic activation). To determine whether the predominance of a NE-induced polycystic condition after NGF is responsible for the PCO phenotype, rats were exposed to an intraovarian administration of carbachol (100 μM), a muscarinic cholinergic agonist not degraded by AChE. Decreased the number of follicular cysts and increased the number of corpora lutea, reinforcing that cholinergic activity of the ovary participates in controlling its functions. Although NGF increased the biosynthetic capacity for ACh, it was not available to act in the ovary. Hence, NGF also regulates the ovarian cholinergic system, implying that NGF is the main regulator of the dual autonomic control. These findings highlight the need for research in the treatment of PCO syndrome by modification of locally produced ACh as an regulator of follicular development.
卵巢的功能受自主神经系统（交感和胆碱能卵巢内系统）的影响，该系统有助于调节类固醇分泌、卵泡发育和排卵。目前尚不清楚激活这两个系统的初始信号是什么。神经生长因子（NGF）是第一个被发现调节卵巢去甲肾上腺素能神经元和中枢神经系统胆碱能神经元的神经营养因子。本研究旨在确定 NGF 是否是激活卵巢交感和胆碱能系统的参与神经营养因子之一，以及其在正常或病理状态下卵泡发育中的作用。戊酸雌二醇（多囊卵巢[PCO]表型模型）的给药增加了去甲肾上腺素（NE）（通过 NGF 依赖性机制）和乙酰胆碱（ACh）水平。NGF 通过渗透微型泵在卵巢内持续 28 天的暴露增加了酪氨酸羟化酶和乙酰胆碱酯酶（AChE，降解 ACh 的酶）的表达，而不影响酶活性，但降低了卵巢 ACh 水平。NGF（100ng/ml，3h）对卵巢的暴露增加了卵巢中胆碱乙酰转移酶和囊泡 ACh 转运体的表达，但对 ACh 水平没有影响。NGF 导致无排卵状态，出现卵泡囊肿和黄体数量减少（对应于去甲肾上腺素能激活）。为了确定 NGF 后 NE 诱导的多囊状态的优势是否是 PCO 表型的原因，将大鼠暴露于卵巢内给予卡巴胆碱（100μM），一种不被 AChE 降解的毒蕈碱样胆碱能激动剂。减少了卵泡囊肿的数量并增加了黄体的数量，这表明卵巢的胆碱能活性参与了其功能的控制。尽管 NGF 增加了 ACh 的生物合成能力，但它在卵巢中无法发挥作用。因此，NGF 还调节卵巢胆碱能系统，这意味着 NGF 是双重自主控制的主要调节剂。这些发现强调了需要通过修饰局部产生的 ACh 作为卵泡发育的调节剂来研究 PCO 综合征的治疗方法。
