Transcriptional activation of the membrane-bound progesterone receptor (mPR) by dioxin, in endocrine-responsive tissues.
We originally identified the membrane-bound progesterone receptor (mPR) using a screening for genes differentially expressed in liver of rats exposed to dioxin. Recent findings have suggested a role for the mPR in sperm cells, ovary, and brain; however, its mechanisms of action are largely unknown. In this study, we examined the expression pattern of the mPR in liver of rats exposed to dioxin and identified possible mechanisms of its regulation. We observed that mPR expression was induced by dioxin, but was also dependent on the hormonal responsiveness of the tissue. In particular, in male, but not female liver, dioxin induced the expression of the mPR. However, in control, untreated female liver the level of mPR transcript was higher than in control males. Moreover, in breast cancer cells MCF-7 dioxin induced mPR expression. Promoter studies using the luciferase assay indicated that a fragment of approximately 350 bp of the mPR promoter was able to induce luciferase activity in the presence of dioxin, suggesting that the presumptive XREs sites contained in this mPR promoter region are responsive to dioxin. Analysis of mPR protein level confirmed the results observed at the RNA level, both in rat liver and MCF-7 cells. Taken together, these observations suggest the existence of a novel cross-talk between steroid and aromatic hydrocarbon receptors (AhR), and underline the importance of the mPR as a mediator of physiologic effects of the sex hormones.
Selmin
Ornella
O
Department of Veterinary Sciences and Microbiology, University of Arizona, Tucson, AZ 87524, USA. selmin@u.arizona.edu
Thorne
Patricia A
PA
Blachere
Francoise M
FM
Johnson
Paula D
PD
Romagnolo
Donato F
DF
D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004147:Dioxins / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000502:physiology; D020218:Response Elements / Q000235:genetics; D012737:Sex Factors; D015533:Transcriptional Activation
D004147:Dioxins; D004967:Estrogens; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D019363:Cytochrome P-450 CYP1A1