Tsafriri A, Reich R
Department of Biological Regulation, The Bernhard Zondek Hormone Research Laboratory, the Weizmann Institute of Science, Rehovot, Israel.
Exp Clin Endocrinol Diabetes. 1999;107(1):1-11. doi: 10.1055/s-0029-1212066.
Ovulation, recurring every reproductive cycle of the mammalian female and triggered by a surge of luteinizing hormone (LH) released from the pituitary is an essential prerequisite for fertilization and subsequent embryonic development. Here we shall review two of the biological responses leading to follicle rupture -- vascular changes and proteolysis. Naturally, our present knowledge is based mainly on work in a few species, such as the rat, the mouse and, to lesser extent the pig and monkeys and observations in the human. Therefore any generalizations to other mammals, should be considered as a working hypothesis yet to be confirmed. The LH surge stimulates, in the preovulatory follicles, a cascade of proteolytic enzymes, including plasminogen activator (PA), plasmin and matrix metalloproteinases (MMPs). These enzymes bring about the degradation of perifollicular matrix and, most notably, the decomposition of the meshwork of collagen fibers which provides the strength to follicular wall. Pharmacological blockage of any of these enzymes resulted in the reduction of ovulation rate. The increased ovarian proteolytic activity associated with ovulation is controlled by locally produced specific inhibitors, plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteases-1 (TIMP-1). The increased synthesis of these two specific proteinase inhibitors in the theca of growing follicles ensures their development by protecting them from enzymes diffusing from ovulatory follicles. The stimulation of ovulation by the gonadotropin results in an increase in follicular blood flow, hyperemia, increase in vascular permeability and a marked increase in follicular volume. These vascular changes and the proteolytic activity are triggered either directly by LH or by local mediators and factors produced in response to the gonadotropic stimulus. These mediators allow the tight coordination of these two cascades culminating in the rupture of follicle wall. We shall review here, briefly, the various mediatory systems that have been implicated in follicle rupture. These include steroids, vascular endothelial growth factor (VEGF), cytokines, eicosanoids, platelet activating factor (PAF), nitric oxide and nitric oxide synthase (NO/NOS), kinins and oxygen radicals.
排卵是哺乳动物雌性每个生殖周期都会发生的现象，由垂体释放的促黄体生成素（LH）激增引发，是受精及后续胚胎发育的必要前提。在此，我们将回顾导致卵泡破裂的两种生物学反应——血管变化和蛋白水解。自然地，我们目前的认知主要基于对少数物种的研究，如大鼠、小鼠，在较小程度上还包括猪、猴子以及对人类的观察。因此，将这些结论推广至其他哺乳动物时，应视为有待证实的工作假设。LH激增会刺激排卵前卵泡中的一系列蛋白水解酶，包括纤溶酶原激活物（PA）、纤溶酶和基质金属蛋白酶（MMPs）。这些酶会导致卵泡周围基质的降解，最显著的是分解为卵泡壁提供强度的胶原纤维网。对这些酶中的任何一种进行药理阻断都会导致排卵率降低。与排卵相关的卵巢蛋白水解活性增加受局部产生的特异性抑制剂——纤溶酶原激活物抑制剂-1（PAI-1）和金属蛋白酶组织抑制剂-1（TIMP-1）控制。生长卵泡的卵泡膜中这两种特异性蛋白酶抑制剂合成增加，通过保护卵泡免受排卵卵泡扩散的酶的影响来确保卵泡的发育。促性腺激素对排卵的刺激会导致卵泡血流量增加、充血、血管通透性增加以及卵泡体积显著增大。这些血管变化和蛋白水解活性要么直接由LH触发，要么由响应促性腺激素刺激而产生的局部介质和因子触发。这些介质使这两个级联反应紧密协调，最终导致卵泡壁破裂。在此，我们将简要回顾与卵泡破裂相关的各种介导系统。这些包括类固醇、血管内皮生长因子（VEGF）、细胞因子、类花生酸、血小板活化因子（PAF）、一氧化氮和一氧化氮合酶（NO/NOS）、激肽和氧自由基。
