The isolation and characterization of estradiol-fatty acid esters in human ovarian follicular fluid. Identification of an endogenous long-lived and potent family of estrogens.
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.
Larner
J M
JM
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 065510.
Pahuja
S L
SL
Shackleton
C H
CH
McMurray
W J
WJ
Giordano
G
G
Hochberg
R B
RB
D016718:Arachidonic Acid / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004952:Esters; D004958:Estradiol / Q000737:chemistry / Q000302:isolation & purification*; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification*; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry*; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000032:analysis; D019301:Oleic Acid; D009829:Oleic Acids / Q000032:analysis; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000032:analysis; D011863:Radioimmunoassay; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013229:Stearic Acids / Q000032:analysis
D004952:Esters; D005227:Fatty Acids; D008041:Linoleic Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D013229:Stearic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; D019308:Palmitic Acid; C031183:stearic acid; D004958:Estradiol; D019787:Linoleic Acid