Pulmonary neuroendocrine cells in nitrofen-induced diaphragmatic hernia and the effect of prenatal glucocorticoids.
The high mortality associated with congenital diaphragmatic hernia (CDH) is due to pulmonary hypoplasia and hypertension, structural and functional abnormalities which can to some extent be ameliorated by prenatal administration of glucocorticoids. In the hypoplastic, hypertensive lungs of neonatal rats in which CDH has been induced by nitrofen, those pulmonary neuroendocrine cells (PNCs) containing calcitonin gene-related peptide (CGRP) increase in number, and it has been suggested that this might be due to inhibition of secretion of the peptide, the consequent decrease in its vasodilatory effects contributing to the hypertension. Whether this increase affects the entire population of PNCs, however, and how these cells are affected by administration of prenatal glucocorticoids, is unknown. As revealed by immunolabelling for protein gene product (PGP) 9.5, a general marker of NCs and expressed per cm2 tissue section, the total PNC population in rats with nitrofen-induced CDH was significantly greater than in controls receiving only olive oil (672 vs 375/cm2, P = 0.03) and was further increased (824 per cm2) in animals treated prenatally with dexamethasone (n = 8 in all groups). The increase in the total PNC population in rats with CDH is similar in magnitude to that described for the CGRP-containing subpopulation. Since the major role of the products of PNCs is now thought to be the regulation of development of pulmonary tissues and their response to injury, it is probable that the expansion of their population in the abnormal lungs associated with CDH is an adaptive response to pulmonary maldevelopment, a response possibly augmented by exogenous corticosteroids.
Gosney
J R
JR
Department of Pathology, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, England.
Okoye
B O
BO
Lloyd
D A
DA
Losty
P D
PD
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006548:Hernia, Diaphragmatic / Q000139:chemically induced; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000166:cytology / Q000196:embryology*; D009490:Neurosecretory Systems / Q000166:cytology* / Q000196:embryology; D010647:Phenyl Ethers; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D010647:Phenyl Ethers; D003907:Dexamethasone; D015740:Calcitonin Gene-Related Peptide; C007350:nitrofen