Dissen G A, Lara H E, Leyton V, Paredes A, Hill D F, Costa M E, Martinez-Serrano A, Ojeda S R
Division of Neuroscience, Oregon Regional Primate Research Center-Oregon Health Sciences University, Beaverton 97006-3448, USA.
Endocrinology. 2000 Mar;141(3):1073-82. doi: 10.1210/endo.141.3.7396.
A single injection of estradiol valerate induces a form of cystic ovary resembling some aspects of the human polycystic ovarian syndrome. Preceding the development of follicular cysts, there is an increase in intraovarian synthesis of nerve growth factor (NGF) and the low affinity NGF receptor (p75 NGFR). Selective blockade of NGF actions and p75 NGFR synthesis in the ovary restored estrous cyclicity and ovulatory capacity in estradiol valerate-treated rats, suggesting that an increase in NGF-dependent, p75 NGFR-mediated actions within the ovary contributes to the development of cystic ovarian disease. We have tested this hypothesis by grafting NGF-producing neural progenitor cells into the ovary of juvenile rats that have been induced to ovulate precociously by a single injection of PMSG. The NGF-producing cells, detected by their content of immunoreactive p75 NGFR material, were found scattered throughout the ovary with some of them infiltrating the granulosa cell compartment of large, precystic follicles. Ovarian NGF content was 2-fold higher than in the ovary of rats receiving control cells. Estrous cyclicity was disrupted, with the animals showing prolonged periods of persistent estrus, and an almost continuous background of vaginal cornified cells at other phases of the estrous cycle. Morphometric analysis revealed that the presence of NGF-producing cells neither reduced the total number of corpora lutea per ovary nor significantly increased the formation of follicular cysts. However, the ovaries receiving these cells showed an increased incidence of precystic, type III follicles, accompanied by a reduced number of healthy antral follicles, and an increased size of both healthy and atretic follicles. These changes in follicular dynamics were accompanied by a selective increase in serum androstenedione levels. The results show that an abnormally elevated production of NGF within the ovary suffices to initiate several of the structural and functional alterations associated with the development of follicular cysts in the rat ovary.
单次注射戊酸雌二醇可诱发一种囊性卵巢，其在某些方面类似于人类多囊卵巢综合征。在卵泡囊肿形成之前，卵巢内神经生长因子（NGF）和低亲和力NGF受体（p75 NGFR）的合成会增加。选择性阻断卵巢中NGF的作用和p75 NGFR的合成可恢复戊酸雌二醇处理大鼠的发情周期和排卵能力，这表明卵巢内依赖NGF、由p75 NGFR介导的作用增加有助于囊性卵巢疾病的发展。我们通过将产生NGF的神经祖细胞移植到经单次注射孕马血清促性腺激素（PMSG）诱导早熟排卵的幼鼠卵巢中来验证这一假设。通过免疫反应性p75 NGFR物质的含量检测到的产生NGF的细胞散布于整个卵巢，其中一些细胞浸润到大的、囊肿前期卵泡的颗粒细胞区。卵巢中的NGF含量比接受对照细胞的大鼠卵巢高2倍。发情周期被打乱，动物表现出持续发情期延长，在发情周期的其他阶段阴道角化细胞几乎持续存在。形态计量学分析显示，产生NGF的细胞的存在既没有减少每个卵巢黄体的总数，也没有显著增加卵泡囊肿的形成。然而，接受这些细胞的卵巢中囊肿前期III型卵泡的发生率增加，同时健康的窦状卵泡数量减少，健康卵泡和闭锁卵泡的大小均增加。卵泡动力学的这些变化伴随着血清雄烯二酮水平的选择性升高。结果表明，卵巢内NGF的异常过量产生足以引发与大鼠卵巢卵泡囊肿发展相关的一些结构和功能改变。
