Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia.
Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions. In this study, ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH). Additionally, the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested. In normal lungs, ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age. In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls. Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups. Furthermore, the growth hormone, secretagogue receptor (GHSR1a), could not be amplified from human or rat fetal lungs by RT-PCR. In conclusion, of all the lungs studied so far, the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin. Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia, most likely through a GHSR1a-independent pathway.
Santos
Marta
M
Life and Health Sciences Research Institute, University of Minho, Portugal.
Bastos
Pedro
P
Gonzaga
Silvia
S
Roriz
José-Mário
JM
Baptista
Maria J
MJ
Nogueira-Silva
Cristina
C
Melo-Rocha
Gustavo
G
Henriques-Coelho
Tiago
T
Roncon-Albuquerque
Roberto
R
Leite-Moreira
Adelino F
AF
De Krijger
Ronald R
RR
Tibboel
Dick
D
Rottier
Robbert
R
Correia-Pinto
Jorge
J
D000818:Animals; D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology; D005865:Gestational Age; D054439:Ghrelin; D006540:Herbicides / Q000633:toxicity*; D006548:Hernia, Diaphragmatic / Q000139:chemically induced; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D017403:In Situ Hybridization; D008168:Lung / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D036361:Peptide Hormones / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D010647:Phenyl Ethers / Q000633:toxicity*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D054440:Receptors, Ghrelin
D054439:Ghrelin; D006540:Herbicides; D036361:Peptide Hormones; D010647:Phenyl Ethers; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C007350:nitrofen