Larner J M, Pahuja S L, Shackleton C H, McMurray W J, Giordano G, Hochberg R B
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 065510.
J Biol Chem. 1993 Jul 5;268(19):13893-9.
The estradiol-fatty acid esters are highly potent and long-lived estrogens that were first isolated and identified from in vitro biosynthetic experiments (Mellon-Nussbaum S., Ponticorvo, L., Schatz, F., and Hochberg, R. B. (1982) J. Biol. Chem. 257, 5678-5684). Other studies have indicated that these esters exist endogenously, but the evidence is indirect, resting solely on the presence of a nonpolar saponifiable metabolite. Although there are similar reports of other naturally occurring fatty acid esters of biologically active steroid hormones, likewise, none has been isolated and characterized. In this study we have found that follicular fluid from the ovaries of women stimulated with gonadotrophins contains relatively large amounts of a nonpolar saponifiable derivative of estradiol (approximately 10(-7)M), which we presumed to be fatty acid esters. Using a combination of chromatographic techniques we isolated these estradiol metabolites and identified them by mass spectral analysis. They are a mixture of five different estradiol-17 fatty acid esters. The amount of each present was determined by separating the esters by reversed phase high performance liquid chromatography and then quantifying each peak by radioimmunoassay and UV absorption. The esters of estradiol are predominantly unsaturated, with linoleate the most abundant comprising 43% of the total. The other esters are: palmitate (20%), arachidonate (19%), oleate (14%), and stearate (4%). Thus these studies conclusively demonstrate the existence of these unusually powerful estrogens.
雌二醇脂肪酸酯是高效且长效的雌激素，最初是从体外生物合成实验中分离并鉴定出来的（梅隆 - 努斯鲍姆S.、庞蒂科沃、L.、沙茨、F.和霍奇伯格、R.B.（1982年）《生物化学杂志》257卷，5678 - 5684页）。其他研究表明这些酯类内源性存在，但证据是间接的，仅基于一种非极性可皂化代谢物的存在。尽管有关于生物活性甾体激素的其他天然存在的脂肪酸酯的类似报道，但同样，没有一种被分离和表征。在本研究中，我们发现用促性腺激素刺激的女性卵巢卵泡液中含有相对大量的雌二醇非极性可皂化衍生物（约10⁻⁷M），我们推测其为脂肪酸酯。我们使用多种色谱技术的组合分离了这些雌二醇代谢物，并通过质谱分析对其进行了鉴定。它们是五种不同的雌二醇 - 17脂肪酸酯的混合物。通过反相高效液相色谱分离这些酯，然后通过放射免疫测定和紫外吸收对每个峰进行定量，从而确定每种酯的含量。雌二醇酯主要是不饱和的，其中亚油酸酯含量最高，占总量的43%。其他酯类为：棕榈酸酯（20%）、花生四烯酸酯（19%）、油酸酯（14%）和硬脂酸酯（4%）。因此，这些研究确凿地证明了这些异常强大的雌激素的存在。
