Developmental regulation of the lung in preparation for life after birth: hormonal and nutritional manipulation of local glucocorticoid action and uncoupling protein-2.
Glucocorticoid action has a major role in regulating fetal and postnatal lung development, although its impact on mitochondrial development is less well understood. Critically, the consequences of any change in glucocorticoid action and mitochondrial function in early life may not be limited to the postnatal period, but may extend into later life. This paper focuses on more recent findings on the impact of ontogeny, fetal cortisol status, maternal nutrient restriction and postnatal leptin administration on mitochondrial uncoupling protein (UCP)-2, glucocorticoid receptor (GR) and 11 beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) isoform abundance in the lung. For example, in sheep, GR and 11betaHSD1 mRNA are maximal at 140 days' gestation (term approximately 147 days), while UCP2 mRNA peaks at 1 day after birth and then decreases with advancing age. In the fetus, chronic umbilical cord compression enhances the abundance of these genes, an outcome that can also be produced after birth following chronic, but not acute, leptin administration. Irrespective of the timing of maternal nutrient restriction in pregnancy, glucocorticoid sensitivity and UCP2 abundance are both upregulated in the lungs of the resulting offspring. In conclusion, prenatal and postnatal endocrine challenges have distinct effects on mitochondrial development in the lung resulting from changes in glucocorticoid action, which can persist into later life. As a consequence, changes in glucocorticoid sensitivity and mitochondrial protein abundance have the potential to be used to identify those at greatest risk of developing later lung disease.
Gnanalingham
M G
MG
Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham NG7 2UH, UK.
Mostyn
A
A
Gardner
D S
DS
Stephenson
T
T
Symonds
M E
ME
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D005938:Glucocorticoids / Q000378:metabolism*; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D012756:Sheep; D000071246:Uncoupling Protein 2
D005938:Glucocorticoids; D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071246:Uncoupling Protein 2