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Elevated FGF21 leads to attenuated postnatal linear growth in preterm infants through GH resistance in chondrocytes.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2014 Nov; Vol. 99 (11), pp. E2198-206. Date of Electronic Publication: 2014 Aug 19. - Publication Year :
- 2014
-
Abstract
- Context: The hormone fibroblast growth factor 21 (FGF21) is a key metabolic regulator in the adaptation to fasting. In food-restricted mice, inhibition of skeletal growth is mediated by the antagonistic effect of FGF21 on GH action in the liver and growth plate.<br />Objective: The objective of the study was to assess the role of FGF21 in growth regulation in humans using postnatal growth failure of very preterm infants as a model.<br />Design: FGF21 levels were measured serially in very preterm infants, and their linear growth evaluated from birth to term-equivalent age. Primary chondrocytes obtained from pediatric donors were used to test whether FGF21 can directly interfere with GH signaling.<br />Results: A negative association (β -.415, P < .005, linear regression model) of FGF21 levels with the change in SD score for length was found. In primary chondrocytes, FGF21 upregulated basal and GH-induced SOCS2 expression and inhibited GH-induced signal transducer and activator of transcription 5 (STAT5) phosphorylation as well as GH-induced COLII and ALP expression. Finally, FGF21 inhibited GH-induced IGF-1 expression and cell proliferation, indicating GH resistance. However, FGF21 did not affect IGF-1-induced cell proliferation.<br />Conclusions: Elevated FGF21 serum levels during the first weeks of life are independently associated with postnatal growth failure in preterm infants. Furthermore, our data provide mechanistic insights into GH resistance secondary to prematurity and may offer an explanation for the growth failure commonly seen in chronic conditions of childhood.
- Subjects :
- Cells, Cultured
Chondrocytes cytology
Chondrocytes drug effects
Female
Fibroblast Growth Factors pharmacology
Growth Disorders blood
Humans
Infant
Infant, Premature blood
Male
Signal Transduction drug effects
Signal Transduction physiology
Chondrocytes metabolism
Fibroblast Growth Factors blood
Growth Disorders metabolism
Human Growth Hormone metabolism
Infant, Premature growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 99
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 25137423
- Full Text :
- https://doi.org/10.1210/jc.2014-1566