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Perinatal expression of IGFBPs in rat lung and its hormonal regulation in fetal lung explants
J K van de Wetering1, R H Elfring, M A Oosterlaken-Dijksterhuis
1Laboratory of Veterinary Biochemistry, Utrecht University, The Netherlands.
Insights
Lung development involves insulin-like growth factor (IGF) binding proteins (IGFBPs). Glucocorticoids regulate IGFBP expression in fetal rat lungs, suggesting a role in lung development and glucocorticoid action.
Area of Science:
- Endocrinology
- Developmental Biology
- Molecular Biology
Background:
- Insulin-like growth factor (IGF) binding proteins (IGFBPs) play crucial roles in regulating IGF bioavailability.
- Understanding IGFBP regulation is key to deciphering lung development and glucocorticoid effects.
Purpose of the Study:
- To investigate the developmental expression patterns of IGFBP mRNAs in perinatal rat lungs.
- To examine the influence of hormones, specifically glucocorticoids, on IGFBP expression in fetal lung explants.
Main Methods:
- Measurement of IGFBP mRNA abundance in perinatal rat lungs.
- Analysis of IGFBP mRNA levels in hormone-free fetal rat lung explant cultures.
- Assessment of the effects of dexamethasone and 3,3',5-triiodothyronine on IGFBP expression in explants.
Main Results:
- IGFBP-2 to -5 mRNA levels in explants mimicked in vivo developmental patterns.
- IGFBP-6 mRNA showed a different pattern in vitro compared to in vivo.
- Dexamethasone decreased IGFBP-2 to -5 mRNA abundance and IGFBP-3 and -4 protein production, but increased IGFBP-6 mRNA.
- 3,3',5-triiodothyronine had no significant effect on IGFBP expression.
Conclusions:
- Glucocorticoids likely regulate the developmental expression of specific IGFBPs in the lung.
- The IGF system may mediate some physiological effects of glucocorticoids on lung development.
- Explant cultures effectively model in vivo developmental regulation for most IGFBPs, with exceptions for IGFBP-6.
Abstract:
To gain more insight into the regulation of the expression of insulin-like growth factor (IGF) binding proteins (IGFBPs) in the lung, the developmental patterns of the abundance of the mRNAs encoding IGFBPs were measured in the perinatal rat lung and in explant cultures of fetal rat lung. In hormone-free explant cultures, the levels of the mRNAs encoding IGFBP-2 through -5 changed with a pattern similar to that occurring in vivo (although in the case of IGFBP-3 to -5 at a faster rate), indicating that the developmental regulation of the expression of these IGFBPs in perinatal lung is mimicked in the explants. For the IGFBP-6 mRNA level, the pattern in vitro differed from that in vivo. In the explant cultures, dexamethasone decreased the production of IGFBP-3 and -4 and decreased the abundance of the mRNAs encoding IGFBP-2 to -5 but increased the abundance of IGFBP-6 mRNA. These observations indicate that glucocorticoids may be involved in the developmental regulation of the expression of these components of the IGF system and that the IGF system may be involved in the physiological effects of glucocorticoids on lung development. No appreciable effects of 3,3',5-triiodothyronine on the expression of the IGFBPs were observed.