Regulation of expression of the retinoic acid metabolizing enzyme CYP26A1 in uteri of ovariectomized mice after treatment with ovarian steroid hormones
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Regulation of expression of the retinoic acid metabolizing enzyme CYP26A1 in uteri of ovariectomized mice after treatment with ovarian steroid hormones. / Fritzsche, Britta; Vermot, Julien; Neumann, Ulrike; Schmidt, Anja; Schweigert, Florian J; Dollé, Pascal; Rühl, Ralph.
In: MOL REPROD DEV, Vol. 74, No. 2, 02.2007, p. 258-64.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research
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TY - JOUR
T1 - Regulation of expression of the retinoic acid metabolizing enzyme CYP26A1 in uteri of ovariectomized mice after treatment with ovarian steroid hormones
AU - Fritzsche, Britta
AU - Vermot, Julien
AU - Neumann, Ulrike
AU - Schmidt, Anja
AU - Schweigert, Florian J
AU - Dollé, Pascal
AU - Rühl, Ralph
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
KW - Animals
KW - Cytochrome P-450 Enzyme System
KW - Endometrium
KW - Epithelial Cells
KW - Estrogens
KW - Female
KW - Gene Expression Regulation, Enzymologic
KW - In Situ Hybridization
KW - Mice
KW - Ovariectomy
KW - Pregnancy
KW - Progesterone
KW - RNA, Messenger
KW - Retinoic Acid 4-Hydroxylase
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Transcription, Genetic
KW - Tretinoin
KW - Uterus
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/mrd.20526
DO - 10.1002/mrd.20526
M3 - SCORING: Journal article
C2 - 16955405
VL - 74
SP - 258
EP - 264
IS - 2
ER -