Steffensen Knut R, Robertson Kirsten, Gustafsson Jan-Ake, Andersen Claus Yding
Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Sweden.
Mol Cell Endocrinol. 2006 Aug 15;256(1-2):9-16. doi: 10.1016/j.mce.2006.03.044. Epub 2006 Aug 8.
Cholesterol precursors act as activators of the nuclear hormone receptor, liver X receptor (LXR). One of these LXR-activating ligands is meiosis activating sterol (MAS), which also induces resumption of meiosis in oocytes from mice in vitro. Whether LXR participates in the regulation of oocyte maturation and whether the expression of either one of the two paralogues of LXR (alpha and beta) affect fertility of mice has, however, not yet been clarified. Female mice lacking Lxra, Lxrb or both genes (Lxra(-/-), Lxrb(-/-) and Lxrab(-/-), respectively) conceive less frequently and have significantly fewer pups per litter as compared to wild type mice. Both Lxra and Lxrb mRNA were found to be expressed in mouse oocytes. The relative expression of, in particular, Lxrb was almost two orders of magnitude higher than in liver, brain and testis. A water-soluble LXR agonist caused naked oocytes, but not cumulus enclosed oocytes (CEO), from wild type mice to resume meiosis significantly more often than control oocytes. Follicle stimulating hormone (FSH) is a potent stimulator of meiosis in CEO from wild type mice, but was without effect in mice lacking both Lxr genes. Zymosterol, a MAS active substance, induced resumption of meiosis in oocytes from Lxrab(-/-) mice, but significantly less effectively than in oocytes from wild type mice. Taken together, LXRs seem to affect ovarian function, suggesting specific roles of cholesterol precursors in regulation of female reproduction.
胆固醇前体作为核激素受体——肝脏X受体（LXR）的激活剂。这些LXR激活配体之一是减数分裂激活甾醇（MAS），它在体外也能诱导小鼠卵母细胞恢复减数分裂。然而，LXR是否参与卵母细胞成熟的调节，以及LXR的两个旁系同源物（α和β）之一的表达是否影响小鼠的生育能力，尚未得到阐明。与野生型小鼠相比，缺乏Lxra、Lxrb或这两个基因（分别为Lxra(-/-)、Lxrb(-/-)和Lxrab(-/-)）的雌性小鼠受孕频率较低，每窝幼崽数量也明显较少。发现Lxra和Lxrb mRNA均在小鼠卵母细胞中表达。特别是Lxrb的相对表达量比肝脏、大脑和睾丸中的表达量高近两个数量级。一种水溶性LXR激动剂使野生型小鼠的裸卵母细胞比对照卵母细胞更频繁地恢复减数分裂，但对卵丘包被卵母细胞（CEO）无效。促卵泡激素（FSH）是野生型小鼠CEO减数分裂的有效刺激剂，但对缺乏两个Lxr基因的小鼠无效。酵母甾醇是一种MAS活性物质，可诱导Lxrab(-/-)小鼠的卵母细胞恢复减数分裂，但效果明显低于野生型小鼠的卵母细胞。综上所述，LXR似乎会影响卵巢功能，提示胆固醇前体在调节雌性生殖中具有特定作用。
