Soodak L K, MacDonald G J, Behrman H R
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
Endocrinology. 1988 Jan;122(1):187-93. doi: 10.1210/endo-122-1-187.
An elevation of ATP levels in luteal cells markedly enhances their response to gonadotropin. In contrast, depletion of ATP in all cells leads to a series of interrelated events that produces irreversible cell injury. Since the corpus luteum has a transient existence, functional regression and involution of this gland play a fundamental role in the regulation of reproduction. The objective of the present studies was to evaluate whether the luteal ATP content may be regulated in an endocrine fashion and whether luteolysis may be linked to depletion of ATP in the corpus luteum in vivo. The present studies show that removal of the pituitary, maintenance of luteal function in hypophysectomized rats with PRL, or acute treatment with prostaglandin F2 alpha had no effect on luteal ATP levels. However, LH produced a rapid and marked decrease in adenine nucleotide levels in both intact and hypophysectomized PRL-replaced rats, whereas GTP levels were unaffected. In pituitary-intact rats, this same effect of LH occurred within 5 min, was maximal (40% depletion) within 30 min, and was sustained for many hours. Depletion of ATP by LH was dose dependent and evident with low doses of LH. In addition, a decrease in luteal ATP levels was seen during functional luteolysis in the rat, which was directly related to a rise in the serum levels of LH, but not FSH. In contrast, LH had no effect on ATP depletion in isolated cells prepared from the total luteinized ovary, or in enriched preparations of luteal cells. Thus, the depletion of ATP by LH in vivo appears to be mediated by intraovarian agents of unknown nature. We suggest that the rise in LH levels that follows functional luteolysis, due to reduced negative feedback by progesterone, produces a rapid decrease in luteal ATP levels which induces irreversible cell damage and, ultimately, involution of the corpus luteum. This effect would, presumably, be exacerbated as LH levels rise to maximum at ovulation or until LH receptors become down-regulated.
黄体细胞中ATP水平的升高显著增强了它们对促性腺激素的反应。相反，所有细胞中ATP的耗竭会导致一系列相互关联的事件，从而产生不可逆的细胞损伤。由于黄体具有短暂的存在期，该腺体的功能衰退和退化在生殖调节中起着重要作用。本研究的目的是评估黄体中的ATP含量是否可以通过内分泌方式进行调节，以及黄体溶解是否可能与体内黄体中ATP的耗竭有关。本研究表明，切除垂体、用催乳素维持垂体切除大鼠的黄体功能或用前列腺素F2α进行急性治疗对黄体ATP水平均无影响。然而，促黄体生成素（LH）使完整和垂体切除并用催乳素替代的大鼠的腺嘌呤核苷酸水平迅速且显著降低，而鸟苷三磷酸（GTP）水平不受影响。在垂体完整的大鼠中，LH的这种相同作用在5分钟内出现，30分钟内达到最大值（耗竭40%），并持续数小时。LH引起的ATP耗竭呈剂量依赖性，低剂量的LH即可产生明显效果。此外，在大鼠功能性黄体溶解过程中观察到黄体ATP水平下降，这与血清LH水平升高直接相关，但与促卵泡生成素（FSH）无关。相反，LH对从完全黄体化卵巢制备的分离细胞或黄体细胞富集制剂中的ATP耗竭没有影响。因此，LH在体内引起的ATP耗竭似乎是由性质不明的卵巢内因子介导的。我们认为，由于孕酮负反馈减少，功能性黄体溶解后LH水平的升高会使黄体ATP水平迅速下降，从而导致不可逆的细胞损伤，并最终导致黄体退化。据推测，随着LH水平在排卵时升至最高或直到LH受体下调，这种作用会加剧。
