Ovarian steroidal response to gonadotropins and beta-adrenergic stimulation is enhanced in polycystic ovary syndrome: role of sympathetic innervation.
Ovarian steroidal response to gonadotropins and beta-adrenergic stimulation is enhanced in polycystic ovary syndrome: role of sympathetic innervation.
复制标题
DOI：
10.1210/endo.133.6.8243293
复制
发表时间：
1993-12
期刊：
影响因子：
4.8
通讯作者：
A. Barria;V. Leyton;S. Ojeda;H. Lara
中科院分区：
文献类型：
--
作者：
A. Barria;V. Leyton;S. Ojeda;H. Lara
单次注射戊酸雌二醇(EV)诱导啮齿动物多囊卵巢综合征(PCOS)，可激活支配卵巢的外周交感神经元。这种激活表现为卵巢神经末梢结合和释放去甲肾上腺素(NE)的能力增加，卵巢NE含量增加，接受儿茶酚胺能神经支配的卵巢隔室中的卵巢β-肾上腺素能受体数量减少。本实验旨在研究交感神经流出增强对卵巢的功能影响。在EV注射60天后，即卵泡囊泡形成时，在体外检测腺体对β-肾上腺素能受体刺激和hCG的类固醇反应。EV处理的大鼠对异丙肾上腺素(一种β-肾上腺素能受体激动剂)的卵巢孕酮和雄激素反应显著增加，而对雌二醇的反应没有变化。然而，在发情周期的任何阶段，基础雌二醇的释放都比正常卵巢释放的最高水平高出50倍。EV处理的大鼠对hCG的卵巢孕酮和雄激素反应增强，对异丙肾上腺素和hCG的反应也是如此。切断卵巢上神经(SON)，可显著降低所有三种类固醇对β-肾上腺素能和促性腺激素刺激的夸大反应。SON切断也降低了EV治疗引起的卵巢去甲肾上腺素水平的升高，并导致了β-肾上腺素受体的上调。最重要的是，SON横切术恢复了发情周期和排卵能力。结果表明，PCOS患者卵巢类固醇产量的增加至少部分是由于该腺对儿茶酚胺能和促性腺激素刺激的反应性增强。切断SON恢复正常反应的能力表明，类固醇输出的改变是去甲肾上腺素能神经支配卵巢的选择性成分错乱激活的结果。这些发现支持这样一个概念，即卵巢神经源性控制的改变有助于多囊卵巢综合征的病因。
Experimental induction of a polycystic ovarian syndrome (PCOS) in rodents by the administration of a single dose of estradiol valerate (EV) results in activation of the peripheral sympathetic neurons that innervate the ovary. This activation is evidenced by an increased capacity of ovarian nerve terminals to incorporate and release norepinephrine (NE), an increase in ovarian NE content, and a decrease in ovarian beta-adrenergic receptor number in the ovarian compartments receiving catecholaminergic innervation. The present experiments were undertaken to examine the functional consequences of this enhanced sympathetic outflow to the ovary. The steroidal responses of the gland to beta-adrenergic receptor stimulation and hCG were examined in vitro 60 days after EV administration, i.e. at the time when follicular cysts are well established. EV-treated rats exhibited a remarkable increase in ovarian progesterone and androgen responses to isoproterenol, a beta-adrenergic receptor agonist, with no changes in estradiol responsiveness. Basal estradiol release was, however, 50-fold higher than the highest levels released from normal ovaries at any phase of the estrous cycle. The ovarian progesterone and androgen responses to hCG were enhanced in EV-treated rats, as were the responses to a combination of isoproterenol and hCG. Transection of the superior ovarian nerve (SON), which carries most of the catecholaminergic fibers innervating endocrine ovarian cells, dramatically reduced the exaggerated responses of all three steroids to both beta-adrenergic and gonadotropin stimulation. SON transection also reduced the elevated levels of ovarian NE resulting from EV treatment and caused up-regulation of beta-adrenoreceptors. Most importantly, SON transection restored estrous cyclicity and ovulatory capacity. The results indicate that the increased output of ovarian steroids in PCOS is at least in part due to an enhanced responsiveness of the gland to both catecholaminergic and gonadotropin stimulation. The ability of SON transection to restore a normal response indicates that the alteration in steroid output results from a deranged activation of selective components of the noradrenergic innervation to the ovary. These findings support the concept that an alteration in the neurogenic control of the ovary contributes to the etiology of PCOS.