ANGIOTENSIN II--AN INTRAOVARIAN REGULATORY PEPTIDE

我们最近发现调节肽的受体 血管紧张素II（血管紧张素II）存在于颗粒细胞层， 几个，但不是所有发育中的大鼠卵泡。 我们还 证明：1）Ang II引起分泌增加， 雌二醇-17 β从大鼠卵巢;和2）这两个血管紧张素II 和血管紧张素I转换酶（ACE）存在于大鼠中 卵巢 总的来说，这些研究首次表明， Ang Ⅱ可能是卵泡生长的自分泌或旁分泌调节因子， 雌激素水平 因为卵泡雌激素水平对于 优势卵泡的发育，我们假设， 卵泡对Ang Ⅱ的反应性可能在选择中起作用 和维持优势卵泡。 我们建议：a）确定Ang II的细胞机制- 介导的雌二醇-17 β分泌，因为功能性 卵巢中血管紧张素II的反应是整体治疗的关键部分 假设; B）确定血管紧张素能输入是否与血管紧张素受体的活性有关。 大鼠卵巢是通过研究慢性血管紧张素 II受体阻断剂和ACE抑制剂对 在几个连续的发情周期中排卵; c）确定， 使用体外放射自显影术，无论是给定的卵泡， 含有FSH受体也含有Ang II受体，因为 已知卵泡对FSH的反应性对于 排卵前卵泡的发育; d）确定是否局部 产生的血管紧张素II有助于卵巢功能，通过检查 血管紧张素Ⅱ受体拮抗剂对基础雌二醇-17 β的影响 发情期不同阶段卵巢切片的分泌物 e）将类固醇生成的功能变化与 对局部产生的Ang II的反应与卵巢 发情周期中的肾素和血管紧张素II水平; f）检查是否 颗粒细胞功能的自分泌或旁分泌调节 血管紧张素II在卵泡内通过定义一种功能性的肾素- 颗粒细胞原代培养物中的血管紧张素系统; g）研究卵巢颗粒层肾素的调节， 血管紧张素系统雌二醇-17 β。 在我们对卵巢癌的认识上， 卵泡选择过程。 研究确定了 启动和维持优势卵泡可能具有 对我们理解生育障碍有重要意义。 拟议的研究旨在提供第一步， 确定血管紧张素II在卵巢功能中的作用，并应 最终证明是有用的，在了解卵泡 人类卵巢的选择过程。

We have recently shown that receptors for the regulatory peptide Ang II (angiotensin II) are present on the granulosa cell layer of several, but not all developing rat ovarian follicles. We have also demonstrated: 1) that Ang II causes an increase in the secretion of estradiol-17 beta from the rat ovary; and 2) that both Ang II and angiotensin I converting enzyme (ACE) are present in the rat ovary. Collectively, these studies suggest, for the first time, that Ang II may be an autocrine or paracrine regulator of follicular estrogen levels. Because follicular estrogen levels are critical for the development of dominant follicles, we hypothesize that follicular responsiveness to Ang II may play a role in the selection and maintenance of dominant follicles. We propose: a) to define the cellular mechanism of Ang II- mediated estradiol-17 beta secretion, since the functional response of Ang II in the ovary is a key part of the overall hypothesis; b) to determine whether angiotensinergic input to the rat ovary is consequential by studying the effects of chronic Ang II receptor blockade and ACE inhibition on the incidence of ovulation over several consecutive estrus cycles; c) to determine, using in vitro autoradiography, whether given follicles that contain FSH receptors also contain Ang II receptors, because follicular responsivity to FSH is known to be important for the development of preovulatory follicles; d) to determine if locally produced Ang II contributes to ovarian function by examining the effects of Ang II receptor antagonist on basal estradiol-17 beta secretion from ovarian slices during different phases of the estrus cycle; e) to correlate functional changes in steroidogenic responses to locally produced Ang II with variations in ovarian renin and Ang II levels during the estrus cycle; f) to examine if autocrine or paracrine modulation of granulosa cell function by Ang II occurs within the follicle by defining a functional renin- angiotensin system in primary cell cultures of the granulosa cell; and g) to study the regulation of the ovarian granulosa renin- angiotensin system by estradiol-17 beta. There are considerable gaps in our understanding of ovarian follicular selection processes. Studies defining the factors that initiate and maintain dominant follicles are likely to have an important bearing on our understanding of fertility disorders. The studies proposed are designed to provide the first steps toward defining the role of Ang II in ovarian function, and should ultimately prove to be useful in understanding the follicular selection processes in the human ovary.