Estradiol Regulates Gonadotropin-Releasing Hormone (GnRH) and its Receptor Gene Expression and Antagonizes the Growth Inhibitory Effects of GnRH in Human Ovarian Surface Epithelial and Ovarian Cancer Cells<sup>1</sup>
Notice bibliographique
Résumé
In the present study, we investigated the expression of estrogen receptors (ERalpha and ERbeta) in human ovarian surface epithelial (hOSE) cells and the ovarian cancer cell line, OVCAR-3, and provided novel evidence that estrogen may have a growth regulatory effect in these cells. Expression levels of ERalpha messenger RNA (mRNA) were 1.5-fold higher in OVCAR-3 cells than in hOSE cells, as revealed by semiquantitative RT-PCR and Southern blot analysis. A significant increase (3.3-fold) in ERss mRNA levels was observed in OVCAR-3 cells compared with hOSE cells. In parallel with mRNA levels, expression levels of ERalpha and ERbeta proteins were also higher in OVCAR-3 cells compared with hOSE cells. We recently proposed that GnRH and its receptor may have an autocrine role in hOSE and ovarian cancer cells. To determine whether estrogen regulates GnRH and GnRH receptor (GnRHR), hOSE and OVCAR-3 cells were treated with various concentrations of 17beta-estradiol for 24 h. Expression levels of GnRH and GnRHR mRNA were examined using quantitative and competitive RT-PCR, respectively. Treatment with 17beta-estradiol induced a significant down-regulation of GnRH mRNA in OVCAR-3 cells, but not in hOSE cells and of GnRHR mRNA in both hOSE and OVCAR-3 cells. Tamoxifen, an estrogen antagonist, prevented the effects of 17ssestradiol, suggesting that estradiol action is mediated via the ER. Finally, the effect of estrogen on the growth of hOSE and OVCAR-3 cells was investigated. The cells were treated with various concentrations of 17ss-estradiol, and the proliferative index of cells was measured using [(3)H]thymidine incorporation and DNA fluorometric assays. 17beta-Estradiol stimulated the growth of OVCAR-3 cells in a dose- and time-dependent manner. In contrast, 17beta-estradiol failed to stimulate the growth of hOSE cells. As estrogen down-regulated GnRH and GnRHR mRNA, we investigated whether estrogen treatment blocks the growth inhibitory effect of a GnRH agonist in OVCAR-3 and hOSE cells. Cells were treated with 17beta-estradiol (10(-7) M) together with (D-Ala(6))-GnRH (10(-7) M), and the proliferative index of cells was measured. Pre- or cotreatment of cells with 17beta-estradiol significantly attenuated the growth inhibitory effect of the GnRH agonist in OVCAR-3 cells, whereas no effect of 17ss-estradiol treatment was observed in hOSE cells. To our knowledge, these results provide the first demonstration of a potential interaction between the estradiol/ER and GnRH/GnRHR systems, which may be important in the growth regulation of normal and neoplastic hOSE cells.
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 ».