RETINOIDS, RETINOIC ACID RECEPTORS, AND CYTOPLASMIC RETINOID-BINDING PROTEINS IN PERINATAL RAT LUNG FIBROBLASTS

The early postnatal life of most mammals marks a period of extensive e nlargement of the alveolar surface area and increase in the elastin co ntent of the lung. The factors that regulate the onset and abatement o f this burst of elastin synthesis have not been identified. Previous s tudies of lipid-laden rat pulmonary interstitial fibroblasts (LIF) hav e shown that their elastin synthesis is increased in vitro by retinoic acid (RA). We hypothesized that temporal changes in the endogenous RA content of LIF may correlate with changes in elastin synthesis by the se cells. LIF were isolated from the lungs of rats at gestational day 19 and postnatal days 2, 4, 8, and 12 and their retinoid contents were quantitated. Retinyl esters were highest at gestational day 19 (2.9 /- 0.6 pmol/10(6) cells, means +/- SE) and decreased to 1.6 +/- 0.2 pm ol by postnatal day 2 (P < 0.05). This decrease in retinyl esters was accompanied by an increase in retinol from 0.4 +/- 0.1 to 2.0 +/- 0.6 pmol/10(6) cells (P < 0.05). RA increased in LIF from 0.07 +/- 0.04 pm ol/10(6) cells at gestational day 19 to 0.29 +/- 0.05 pmol/10(6) cells at postnatal day 2 (P < 0.05) and increased in whole lung tissue from 0.07 +/- 0.04 to 0.29 +/- 0.05 nmol/g, over the same interval. The in crease in RA content was accompanied by an increase in RA receptor (RA R)-beta and -gamma mRNAs. The steady-state mRNA level of cellular reti nol binding protein (CRBP) was high in LIF, relative to whole lung tis sue at day 2. Cellular RA binding protein (CRABP) mRNA rose fourfold f rom day 2 to day 8 and then fell by day 12. In summary, RA, RAR, and C RBP mRNA in LIF are highest before the period of maximal elastin synth esis, which occurs at postnatal days 8 and 12. These findings are cons istent with the hypothesis that endogenous RA could contribute to the postnatal increase in elastin production by pulmonary fibroblasts.