POSTNATAL RAT LUNG RETINOIC ACID RECEPTOR (RAR) MESSENGER-RNA EXPRESSION AND EFFECTS OF DEXAMETHASONE ON RAR-BETA MESSENGER-RNA

Retinoids exert multiple effects upon lung differentiation and growth. Although the mechanisms invoked are presently poorly understood, incr easing evidence points to a central role of nuclear retinoic acid rece ptors (RAR). The purpose of this study was to determine RAR mRNA expre ssion profile during postnatal alveolarization, compared with the expr ession in prenatal and adult rat lung, and to describe the effects of dexamethasone (DEX) and oxygen on postnatal lung RAR gene expression. fetal RNA was isolated from lungs of Sprague-Dawley rats on prenatal d ay 19, on postnatal days 1, 3, 7, 10, and 14 of life, and from adults. One subgroup of littermate pups was treated with DEX daily for 3 or 7 days. In a second experiment, rats were exposed to room air or to 95% oxygen for 72 hours, and received either DEX or saline. Northern hybr idization showed that the levels of all RAR subtypes in fetal lung wer e 45% or less of levels at postnatal day 1. The 3.7 kb RAR alpha trans cript levels were lower than day 1 on days 10 and 14 (relative to day 1, day 10 = 0.54 +/- 0.05; day 14 = 0.54 +/- 0.08), but there was no c hange in a 2.7 kb RAR alpha transcript over this time period. By contr ast, RAR beta mRNA levels were significantly higher at days 3, 10, and 14 compared with day 1 (day 3 = 1.79 +/- 0.19; day 10 = 1.41 +/- 0.14 ; day 14 = 1.53 +/- 0.05). Similarly, RAR gamma mRNA expresison levels were higher on day 10 (1.45 +/- 0.09), but by day 14 there was no dif ference from day 1. Adult lung 3.7 kb RAR alpha, 2.7 kb RAR alpha, and RAR gamma were lower than day 1, but RAR beta was significantly great er (3.7 alpha = 0.52 +/- 0.05; 2.7 alpha = 0.49 +/- 0.26; gamma = 0.74 +/- 0.06; beta = 1.63 +/- 0.22). Treatment with DEX prevented the ris e in RAR beta mRNA occurring on day 3 and significantly lowered (0.65 +/- 0.06) the amount of RAR beta mRNA in day 7 lung. Exposure of rat p ups to oxygen caused an increase in RAR beta mRNA (1.21 +/- 0.03). DEX treatment again decreased RAR beta mRNA in both control (0.55 +/- 0.0 6) and oxygen-exposed pups (0.67 +/- 0.12). In addition, 2.7 kb RAR al pha mRNA was decreased with the combination of DEX and oxygen exposure (0.63 +/- 0.06). The differential gene expression profiles and the re sponse to DEX and oxygen of the various members of the RAR family sugg est that each subtype may have a specific role during the period of al veolarization in rat lung. (C) 1995 Wiley-Liss, Inc.