ANGIOTENSIN II--AN INTRAOVARIAN REGULATORY PEPTIDE

我们最近已经证明了调节肽的受体 血管紧张素II(Ang II)存在于卵巢颗粒细胞层。 几个，但不是所有的发育中的大鼠卵泡。我们还有 证明：1)血管紧张素II导致分泌增加 从大鼠卵巢中提取雌二醇-17β；以及2)Ang II 和血管紧张素转换酶(ACE)在大鼠体内 卵巢。总体而言，这些研究首次表明， Ang II可能是卵泡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 优势卵泡的发育，我们假设 卵泡对血管紧张素Ⅱ的反应性可能在选择中起作用 以及维持优势卵泡。 我们建议：a)定义Ang II的细胞机制- 介导的雌二醇-17β分泌，因为功能性 血管紧张素Ⅱ在卵巢中的反应是整个 假设；b)确定血管紧张素能输入是否 慢性血管紧张素转换酶对大鼠卵巢的影响 II受体阻滞剂和血管紧张素转换酶抑制对大鼠心肌梗死发生率的影响 连续几个发情周期的排卵；c)确定， 使用体外放射自显影，无论给予卵泡 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 排卵前卵泡的发育；d)确定局部是否 产生的血管紧张素II有助于卵巢功能 血管紧张素Ⅱ受体拮抗剂对基础雌二醇-17β的影响 动情期不同时期卵巢切片的分泌 周期；e)与类固醇激素生成的功能变化相关 对局部产生的血管紧张素Ⅱ的反应与卵巢的变异 动情周期中肾素和血管紧张素II水平；f)检查 自分泌或旁分泌对颗粒细胞功能的调节 Ang II通过定义功能性肾素在卵泡内发生- 颗粒细胞原代培养中的血管紧张素系统； 和g)研究卵巢颗粒肾素的调节- 血管紧张素系统由雌二醇-17β引起。 我们对卵巢的理解有相当大的差距 卵泡选择过程。定义以下因素的研究 启动和维持优势卵泡很可能有一个 对我们理解生育障碍有重要影响。 建议的研究旨在提供第一步 确定血管紧张素转换酶II在卵巢功能中的作用，应该 最终证明对了解卵泡是有用的 人类卵巢中的选择过程。

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.