A Novel Type of Estrogen Metabolite: Steroid Dimers of Estradiol and Estrone?
Notice bibliographique
Résumé
Extensive metabolism of endogenous estrogens to polar and non-polar metabolites occurs in various tissues besides the major contribution from the liver. Novel non-polar estrogens have been noted following incubation of estradiol (E2) with human liver microsomes; two of them were identified, surprisingly, as diaryl ether dimers of E2. Furthermore, their formation was catalyzed by certain human cytochrome P450 isoforms in the presence of NADPH as co-factor. Their production in vivo and potential biological functions have not been reported, to our knowledge. In studies on estrogen metabolism in reproductive and other tissues in several species we have encountered non-polar metabolites that have remained unidentified. They were less polar than methoxyestrogens on chromatography. Using radiolabeled estrogens as substrates in mammary tissues from adult nulliparous mice, we investigated the possibility that the non-polar metabolites were estrogen dimers. Tritium-labeled E2 and estrone (E1) were used in short-term incubations (1-4h); steroids were recovered from media by solid-phase extraction, as unconjugated and conjugated fractions. Profiles for the unconjugated fractions were obtained by HPLC (acetonitrile:water). Saponification of non-polar metabolites was done with an internal standard of estradiol stearate, followed by HPLC, to eliminate any fatty-acid esters of estrogens. Major amounts of non-polar metabolites were formed in all instances with both substrates; however, saponification yielded no estrogens except from the standard, E2 stearate. Strong acid treatment similarly did not alter the retention time of the non-polar material on subsequent HPLC, suggesting the presence of a very stable metabolite. Subsequently, we have applied the above methodology in a series of examinations of radioactive estrogen metabolites formed with tissues from the reproductive system (vas deferens, cauda epididymis, seminal vesicles and prostate from the boar and stallion; bilaminar and trilaminar equine trophoblast) and non-reproductive tissues (canine skeletal muscle and bone; porcine liver). In all instances the very non-polar metabolites were major products of the incubation and had characteristics that match those of dimers of E2 or E1. The widespread occurrence of a novel form of estrogen metabolite has been raised by these findings and current studies are underway to provide definitive proof of the dimer form and to establish the full identity of these compounds. Their possible biological significance as major metabolites of E2 and E1 will then be a subject for future investigation in both reproductive and non-reproductive systems. This research was supported by NSERC (Canada). (poster)
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».