Abstract
It has been suggested that cellular retinoic acid-binding protein (II) (CRABP(II)) may have a role in the movement of retinoic acid (RA) to its nuclear receptors, thereby enhancing the action of RA in the cells in which it is expressed. RA has also been shown to increase expression of CRABP(II). Previous work from our laboratory has shown that 17 beta-estradiol (E2) administration to prepubertal female rats leads to acquisition of the ability of the lining epithelium to synthesize RA as well as to express CRABP(II). To determine whether this appearance of CRABP(II) was dependent on the production of RA, both E2 and RA were administered to ovariectomized rats. E2 administration induced expression of the CRABP(II) gene in the uterus within 4 h, and this induction was not inhibited by prior administration of puromycin, indicating that the induction was direct. In contrast, RA caused no change in CRABP(II) message level, even at times as late as 48 h after administration. Isolation and analysis of 4.5 kb of the 5'-flanking region of the gene revealed no apparent E2-response element. Using this portion of the gene to drive expression of the luciferase gene in transfected cells allowed identification of a region containing an imperfect estrogen-response element and estrogen-response element half-site, necessary for E2-driven induction. A possible Sp1 binding site in the 5'-flanking region of the CRABP(II) gene was also required for this induction. The ability of E2 to induce expression of CRABP(II) suggests that it can enhance the activity of RA, directly affecting expression of retinoid-responsive genes.
Highlights
The numerous sites of action of retinoic acid, e.g. from reproductive organs to the respiratory system, suggest that there will be several different factors that regulate its synthesis
Recent studies by others have demonstrated an ability of the RA1⁄7CRABP(II) complex to translocate to the nucleus and mediate a direct transfer of retinoic acid (RA) to RARs, an ability not shared by the closely related protein CRABP [6, 7]
In the work presented here, the demonstration that E2 directly induced the expression of CRABP(II) indicates that the effects of E2 on a particular tissue/cell may well result in the induction or modulation of expression of RA-responsive genes, in addition to E2-responsive genes
Summary
This article must be hereby marked “advertisement” in accordance with 18 U.S.C. The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY226560. Animals and Tissue Collection—Female ovariectomized SpragueDawley rats (180 –200 g) were purchased from Harlan Sprague-Dawley Inc. Rats were divided into six groups, each with at least three animals, and injected intraperitoneally with corn oil, puromycin (10 mg/rat), E2 (10 g/rat), puromycin plus E2, RA (500 g/rat), or puromycin plus RA, respectively. Puromycin was injected 30 min before injection with E2 or RA, for those experimental groups. After 4 h, uteri were harvested from the animals for RNA assay; wt, wild type. This paper is available on line at http://www.jbc.org
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