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To assess the effect of retinoids on prostatic ductal branching morphogenesis, anterior prostates from newborn rats were cultured under serum-free conditions for 6 days in the presence of testosterone (10(-8) mM) plus 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (at-RA), or N-4-hydroxyphenyl-retinamide (4-HPR). Measures of morphologic complexity were computed and compared between specimens of different treatment groups.Prostatic ductal growth and branching were inhibited in a dose-dependent fashion by both 13-cis-RA and at-RA, but not by 4-HPR. This inhibitory effect of 13-cis-RA was reversible, as the prostatic ducts resumed branching and growth after removal of retinoic acid from the culture medium. Using reverse transcription polymerase chain reaction, we then investigated the expression of nuclear receptor genes for retinoic acid.This showed the presence of RAR-beta and RAR-gamma in the 0-day prostate, suggesting that the effects of these retinoids on ductal morphogenesis may be via these receptors. |
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