Regulation of expression of the retinoic acid metabolizing enzyme CYP26A1 in uteri of ovariectomized mice after treatment with ovarian steroid hormones.
The retinoic acid (RA) synthesizing enzymes, retinaldehyde dehydrogenases (RALDH), are expressed in specific spatial and temporal patterns in uterine tissues during estrous cycle and early pregnancy in mice. Expression of RALDH1 and 2 has been shown to be induced by estrogen treatment within the uterus. In this study, we determined the influence of progesterone and 17-ss-estradiol on the uterine expression of the RA-metabolizing enzyme CYP26A1 after specific time intervals (1, 4, 24, and 48 hr after treatment of ovariectomized mice). In a following experiment, we investigated the influence of gestagen (promegestone 0.3 mg/kg body weight), estrogen (estradiol 3 microg/kg), their combination, as well as the antagonizing anti-progesterone hormone (RU 486 10 mg/kg) on the uterine expression of CYP26A1. Expression of CYP26A1 was localized using in situ hybridization and quantified using RT-PCR. CYP26A1 mRNA expression was strongly--although transiently--induced in uterine endometrial epithelial and glandular cells after administration of gestagen or the combination of gestagen + estrogen, but not by estrogen alone. These observations were confirmed by semi-quantitative RT-PCR experiments on whole uteri. Thus, we show that the expression of CYP26A1 in endometrial epithelial cells is regulated by progesterone and not significantly influenced by co-administration of estrogen. These data indicate an additional level of hormonal control of endogenous RA levels in the mouse uterus, where its synthesis would rely on estrogen-dependent expression of RALDH enzymes, whereas its active metabolism would be triggered by progesterone-induced CYP26A1 expression.
Fritzsche
Britta
B
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
Vermot
Julien
J
Neumann
Ulrike
U
Schmidt
Anja
A
Schweigert
Florian J
FJ
Dollé
Pascal
P
Rühl
Ralph
R
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D051379:Mice; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D004967:Estrogens; D012333:RNA, Messenger; D011374:Progesterone; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase