Intestinal handling of an oral oleoyl-estrone gavage by the rat.
Adult Zucker lean (Fa/?) female rats received a single 250 nmol oral gavage of 3H-labelled oleoylestrone in 0.2 ml of sunflower oil. After one hour, samples of arterial, portal and suprahepatic blood, and lymph were obtained and fractioned to determine the amount of radioactivity present in the form of free estrone, acyl-estrone and hydrophilic estrone esters in the blood of each vessel. Lipoprotein fractions (chylomicra + VLDL, LDL, HDL and lipoprotein-depleted plasma) were also analysed as well as the distribution of absorbed 3H-estrone in the intestine, specific organs and carcass. About one third of the oleoyl-estrone dose recovered was found in the tissues, mainly in the blood, the rest remaining relatively untouched in the intestinal content. High hypothalamic estrone uptake (compared with the rest of the brain) was observed. Data from non-radioactive estrone measurements showed a similar pattern of absorption and tissue distribution to that obtained by 3H-estrone tracking alone. In both cases, most of the estrone present in the intestinal lumen was absorbed as intact oleoyl-estrone, but a significant part was absorbed as free estrone. There is a net transfer of 3H-estrone into portal blood HDL, and part of the 3H-estrone is also loaded into lymph-carried chylomicra. A large share of free estrone is filtered by the liver, but most of the acyl-estrone absorbed passes unaltered. The oral administration of oleoyl-estrone results in significant absorption of the unaltered molecule, which is transferred to lymph-carried chylomicra and also directly to plasma HDLs. It may be inferred that the HDL fraction contains the physiological carrier of oleoyl-estrone in its role of ponderostat signal.
Esteve
M
M
Centre Especial de Recerca en Nutrició i Ciència dels Aliments, Facultat de Biologia, Universitat de Barcelona, Spain.
Savall
P
P
Blay
M T
MT
Fernández-López
J A
JA
Remesar
X
X
Alemany
M
M
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045166:Estradiol Congeners / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004970:Estrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005766:Gastrointestinal Contents / Q000737:chemistry; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D008074:Lipoproteins / Q000097:blood; D009829:Oleic Acids / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D011924:Rats, Zucker; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D019440:Anti-Obesity Agents; D045166:Estradiol Congeners; D008074:Lipoproteins; D009829:Oleic Acids; D020845:Selective Estrogen Receptor Modulators; D004970:Estrone; C108709:oleoyl-estrone