Transient elevation of messenger RNA encoding gastrin-releasing peptide, a putative pulmonary growth factor in human fetal lung.

Abstract

Gastrin-releasing peptide (GRP), the mammalian homologue of the amphibian peptide bombesin, is present in pulmonary neuroendocrine cells and appears to be a growth factor for both normal and neoplastic pulmonary cells. Previously we have reported the cloning of the messenger RNAs (mRNAs) and gene that encode human GRP. We now report that GRP mRNAs are markedly elevated in human fetal lung during the canalicular phase of pulmonary development (from -16 to 30 wk gestation). By RNA blot and in situ hybridization analyses, GRP mRNAs were first detectable in fetal lung at 9-10 wk, plateaued at levels 25-fold higher than in adult lungs from 16 to -30 wk and then declined to near adult levels by 34 wk gestation. By contrast, GRP peptide levels remain elevated until several months after birth. Consistent with this, in situ hybridization and immunohistochemical studies showed that GRP mRNA and peptide consistently colocalized in early gestation lung but that in neonatal lung, many cells that contained GRP peptide no longer contained GRP mRNA. The transient expression of high levels of GRP mRNAs during an -12-wk phase of fetal lung development suggests that the secretion of GRP or its COOH-terminal peptides from pulmonary neuroendocrine cells may play a role in normal lung development.

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

“…That CD10/NEP inhibition similarly stimulates e 18 fetal lung growth and maturation is consistent with these observations. CD10/NEP inhibition has the greatest effects on fetal lung growth and maturation during the time frame in which endogenous fetal lung CD1O/NEP transcript levels are most abundant (-e [16][17][18]. Although SCH32615 administration in utero from e 12-14 had little effect on e 14 lung growth, significantly greater effects were seen at e 16-18. Similarly, SCH32615 administration from e 15-17 markedly enhanced e 18 fetal lung development.…”

“…In recent studies, these peptides were also shown to stimulate the proliferation and maturation of normal fetal lung. Gastrin-releasing peptide (GRP; mammalian bombesin) transcripts and immunoreactivity were detectable in pulmonary neuroendocrine cells of human fetal lung as early as 8 wk gestation, with peak transcript levels occurring at midgestation ( 17). In murine fetal lung, maximal GRP expression occurred on embryonic days 17 and 18 (e 17-18).…”

“…Gastrin-releasing peptide (GRP; mammalian bombesin) transcripts and immunoreactivity were detectable in pulmonary neuroendocrine cells of human fetal lung as early as 8 wk gestation, with peak transcript levels occurring at midgestation ( 17). In murine fetal lung, maximal GRP expression occurred on embryonic days 17 and 18 (e 17-18). Exogenous bombesin administered to pregnant mice during this time period stimulated the proliferation and maturation of fetal lung as assessed by functional, biochemical, and ultrastructural analyses.…”

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

“…BLP have also been implicated in normal fetal lung development (28,29). GRP mRNAs were first detected in human fetal lung at 9-10 wk gestation, peaked at 16-30 wk at levels 25-fold higher than in adult lungs, and subsequently declined to near adult levels by 34 wk gestation (28).…”

Tissue-specific regulation of gastrin-releasing peptide synthesis, storage and secretion by oestrogen and progesterone

“…Traditionally, GRP is known for the ability to stimulate the release of gastrin and other gastrointestinal hormones in the gut (see Bunnett 1994 for a review). GRP is also found in the brain (Lynn et al 1996), in pulmonary endocrine cells of the foetal lung (Spindel et al 1987) and is produced by a variety of human tumours (Preston et al 1996). Mitogenic effects of GRPlike peptides have been demonstrated for a number of different cell types, including Swiss 3T3 fibroblast cells (Zachary & Rozengurt 1985), ovine foetal chondrocytes (Hill & McDonald 1992) and human endometrial stromal cells in culture (Endo et al 1991).…”