Cellular retinoid binding proteins and nuclear retinoic acid receptors in endometrial epithelial cells

Abstract

Retinoic acid, one of the most potent of the naturally occurring retinoids (retinol and derivatives), is required in vivo for the maintenance of epithelial cell growth. This study describes the pattern of expression of nuclear retinoic acid receptors (RARs and RXRs), and cellular binding proteins for retinol and retinoic acid (CRBP I, CRABP I and II), in endometrial epithelial cells. The effects of retinoic acid on the expression of these receptors in endometrial epithelial cells have also been studied and compared with its effects in endometrial stromal cells. Messenger RNA for RAR-alpha, RAR-beta, RAR-gamma, RXR-alpha, CRBP I and CRABP II was detected by Northern blotting of total RNA extracted from cultured epithelial cells. In comparison with stromal cell RNA that was used as an internal standard, CRBP I appeared to be more abundant in epithelial cells, whereas CRABP II appeared to be more abundant in the stromal cells. This implies that the intracellular concentration of retinoic acid may be maintained at higher levels in epithelial cells compared to stromal cells. In addition, the response of the two cell types to retinoic acid differs: RAR-beta is induced in stromal cells treated with all-trans retinoic acid but not in epithelial cells. From these data we suggest that retinoid physiology differs between endometrial epithelial and stromal cells. Furthermore, by analogy with other studies, we propose that retinoic acid may be maintained at a higher intracellular concentration in endometrial epithelial cells to facilitate differentiation to a glandular phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular retinol binding protein-1 expression in endometrial hyperplasia and carcinoma: diagnostic and possible therapeutic implications

“…6,7,14 Our present data did not allow to explain why CRBP-1 expression is increased in atypical hyperplasia compared to proliferative endometrial epithelium. Nevertheless, some considerations can be made.…”

“…13 In the endometrium, transcript analysis documents significant levels of CRBP-1 throughout the menstrual cycle, whereas those of CRBP-2 vary and possibly mediate the effects of ovarian steroids. 14,15 The availability of a specific antibody 16 allowed to establish that a CRBP-1 positive immunodetection is characteristic of endometrial decidual type stromal cells. 17 Endometrial cancer represents the eighth commonest cause of death from cancer in the female population.…”

Dietary carotenoids in normal and pathological tissues of corpus uteri.

“…CRABP I and II facilitate the mobilisation of retinol from retinyl esters and also the metabolism of retinol to retinoic acid. This proteins could also play a role in the transfer of retinoic acid to the nucleus [17]. In women, the mean CRABP concentration in endometrial carcinomas represents an approximately 4-fold increase over the mean concentration in the normal endometrium and CRBP concentrations tend to be reduced [18].…”

High levels of cellular retinol binding protein-1 expression in leiomyosarcoma: possible implications for diagnostic evaluation

“…Bioavailability of retinol is regulated by the presence of specific cytoplasmic receptors; among these, cellular-retinol binding proteins 1 and 2 (CRBP-1 and -2) are members of the fatty acid-binding proteins (FABP)/CRBP family and have distinct physiologic roles [3,27]. In the endometrium, epithelial and stromal cells express significant levels of mRNA for CRBP-1 throughout the menstrual cycle, whereas levels of CRBP-2 vary and mediate the menstrual cycle effects of ovarian steroids [23,38]. CRBP-1 expression probably reflects the cell requirement for retinol and its active metabolites [5,27].…”