Wuttke W, Pitzel L, Knoke I, Theiling K, Jarry H
Department of Obstetrics and Gynecology, University of Göttingen, Germany.
J Reprod Fertil Suppl. 1997;52:19-29.
The formation, normal function and destruction of corpora lutea are essential features of normal reproduction. Although the formation of corpora lutea from follicles is largely dependent on pituitary gonadotrophins, the process of luteolysis is locally regulated and poorly understood. The corpus luteum consists of several steroidogenic and nonsteroidogenic cell types that interact with each other in a paracrine manner. Under cell culture conditions, large luteal cells that stem from follicular granulosa cells can be identified easily under the microscope and collected individually for single cell RT-PCR. As each of the 120 large luteal cells express the gene encoding 3 beta-hydroxysteroid dehydrogenase, it appears that all large luteal cells are steroidogenic. Large luteal cells also express the oestrogen receptor gene and as they are known to produce oestradiol, it can be concluded that the steroid acts in an auto- or intracrine manner in large luteal cells. Since we showed previously that oestradiol stimulates progesterone release under in vitro and in vivo conditions, it can be concluded that the steroid is an important intraluteally acting luteotrophic signal. At the time of luteal regression, macrophages invade the corpora lutea and their cytokine products, particularly tumour necrosis factor alpha (TNF alpha), appear to be involved in reduced steroid secretion. Indeed, TNF alpha inhibits production of progesterone and oestradiol from cultivated luteal cells. In sows, oestradiol is a strong luteotrophic factor and the production of oestradiol and of its receptor is downregulated by TNF alpha. Thereby, TNF alpha not only exerts direct luteolytic effects but also prevents the luteotrophic effects of oestradiol. Hence, it has an anti-luteotrophic action. In most species, functional luteolysis is accompanied by morphological regression of the corpus luteum. This structural luteolysis also appears to involve TNF alpha, as we have shown in pigs that expression of TNF alpha gene is high during luteolysis. Furthermore, TNF alpha stimulates programmed cell death (apoptosis) in luteal cells kept under culture conditions.
黄体的形成、正常功能及退化是正常生殖的基本特征。尽管卵泡形成黄体很大程度上依赖于垂体促性腺激素，但黄体退化过程是局部调节的，且人们对此了解甚少。黄体由几种以旁分泌方式相互作用的类固醇生成细胞和非类固醇生成细胞类型组成。在细胞培养条件下，源于卵泡颗粒细胞的大黄体细胞在显微镜下很容易识别，并且可以单独收集用于单细胞逆转录聚合酶链反应（RT-PCR）。由于120个大黄体细胞中的每一个都表达编码3β-羟基类固醇脱氢酶的基因，似乎所有大黄体细胞都是类固醇生成细胞。大黄体细胞还表达雌激素受体基因，并且由于已知它们会产生雌二醇，可以得出结论，该类固醇在大黄体细胞中以自分泌或胞内分泌方式起作用。由于我们之前表明雌二醇在体外和体内条件下都会刺激孕酮释放，因此可以得出结论，该类固醇是一种重要的黄体内部起作用的促黄体生成信号。在黄体退化时，巨噬细胞侵入黄体，其细胞因子产物，特别是肿瘤坏死因子α（TNFα），似乎与类固醇分泌减少有关。事实上，TNFα抑制培养的黄体细胞中孕酮和雌二醇的产生。在母猪中，雌二醇是一种强大的促黄体生成因子，而TNFα会下调雌二醇及其受体的产生。因此，TNFα不仅发挥直接的黄体溶解作用，还会阻止雌二醇的促黄体生成作用。因此，它具有抗促黄体生成作用。在大多数物种中，功能性黄体退化伴随着黄体的形态学退化。这种结构性黄体退化似乎也涉及TNFα，正如我们在猪身上所表明的，TNFα基因在黄体退化期间表达很高。此外，TNFα会刺激培养条件下黄体细胞的程序性细胞死亡（凋亡）。
