Intestinal oleoyl-estrone esterase activity in the Wistar rat

Abstract

Low-dose oral oleoyl-estrone (OE) (i.e. in dairy products) is hydrolysed to estrone, which promotes growth and fat deposition. However, pharmacological doses of OE are absorbed largely intact and elicit fat losses. Thus, in order to find out how the intestine handles OE, esterase activity (at pH 5, 7 or 8) was measured in rat stomach, duodenum, jejunum, ileum, cecum, large intestine, and liver using OE as substrate. There were no sex-related differences. Pure pancreatic cholesterol-ester esterase hydrolysed OE even in the absence of taurocholate. The differences in the pH-related activity distribution pattern and selective inhibition and taurocholate dependence show that, in addition to the luminal (i.e. pancreatic) cholesterol-ester esterase, other esterases hydrolyse OE; these combined activities may be sufficient to rapidly dispose of pharmacological doses of OE. Female rats received a tritium-labeled OE gavage; the luminal and tissue label content were measured up to 24 h. The high retention of label in the stomach suggest that this may be a significant site of absorption. The rapid decrease of label in intestinal lumen (and rat tissues) shortly after the administration, hint at rapid absorption and disposal. In conclusion, the high OE-esterase activity and early absorption of OE are indicative of upper gastro-intestinal tract absorption skipping most of the medium-tract esterases.

Oleoyl‐Estrone

“…After an oral load of labelled OE, there is a rapid surge of label in plasma, peaking at a few hours after gavage . This is in agreement with OE being largely taken up in the upper intestine and, especially, the stomach, that in the rat retains label for more than 12 hr . The intestines, essentially jejunum and ileum, contain esterases able to hydrolyze OE.…”

“…Injection of liposomes loaded with OE in vivo result in the appearance of massive amounts of estrone in plasma (a problem circumvented by oral administration), consequence of the massive hydrolysis of the real OE in tissues . In addition, as indicated above, cholesterol–ester esterase also easily hydrolyzes OE . In plasma, however, W is maintained at levels up to 100 nM range and free estrone is kept at less than one hundredth of that, suggesting that, also in vivo, it is well “protected” from ubiquitous esterases.…”

“…Oleoyl‐estrone can be hydrolyzed by a number of intestinal and cellular aryl‐esterases . Cholesterol–ester esterases break up OE with efficiency comparable to that of their breakup of oleoyl‐cholesterol; nevertheless, OE hydrolysis is not dependent on taurocholate as is the hydrolysis of cholesterol–esters …”

“…In addition, pancreatic secretions contain OE‐hydrolyzing cholesterol–ester esterase. The liver also contains powerful aryl‐esterases that break down OE . The combined hydrolyzing power of these enzymes is difficult to associate with most of the OE being absorbed or processed in a way different from free estrone, i.e.…”

Oleoyl-estrone is a precursor of an estrone-derived ponderostat signal

“…[33] or oral [34] administration of labelled OE resulted in an increase of circulating label in plasma. The esterified estrone content of plasma in OE-laden rats also dramatically increased [35].…”