Presented at the Neonatal Society 2002 Spring Meeting.

Hyatt M, Bispham J, Walker D, Stephenson T, Symonds ME

Academic Division of Child Health, School of Human Development, University Hospital, Nottingham NG9 2UH.

Introduction: GH, PRL and IGF-I receptors are all members of the class 1 cytokine superfamily and may perform critical roles in regulating fetal development and postnatal growth (1,2). The onset of GH dependant growth, a major adaptation after birth when growth is no longer dependant on insulin is thought to be established in early neonatal life. The extent to which GH, PRL and IGF-I receptors interact postnatally to regulate growth and the onset of GH dependency is unknown.

Methods: Livers were sampled from late (140 days) gestation fetuses (term = 148 days) and lambs at 1 day, 1 month and 6 months after birth (n = 3-5 per time point). Total RNA was prepared, reverse transcribed and abundance of GH, PRL and IGF-I receptors were measured by polymerase chain reaction (PCR) of reverse transcribed (RT) product using primers specific for each receptor. Genomic DNA contamination was prevented, as all PCR products spanned at least one intron-exon boundary. Results are given as means with their standard errors in arbitrary units as a ratio of the housekeeping gene 18S.

Results: Hepatic IGF-I receptor mRNA abundance peaked at birth (66.3 ± 16.5 a.u), followed by a down-regulation up to 6 months of age (1 month 33.1 ± 7.8 a.u; 6 months 10.1 ± 1.8 a.u (p<0.05)). PRL receptor abundance also peaked at birth, substantially decreasing by 6 months of age. In contrast there was no change in GH receptor abundance up to 6 months of age (birth 38.6 ± 7.2 a.u; 6 months 41.7 ± 9.7 a.u).

Conclusion: The loss of IGF-I and PRL receptors up to 6 months of age in the absence of any change in GH receptor mRNA indicates that the loss of these receptors may be more important in determining the onset of GH dependant growth than alterations in GH receptor per se.

References
1. Bole-Feysot C., Goffin V., Edery M., Binart J., Damotte D., Lucas B.K., Binart N., Kelly P.A. Endocr. Rev. 1999; 19, 225-268.
2. Ormandy C.J., Camus A., Barra J., Damotte D., Lucas B.K., Buteau H., Edery M., Brousse N., Babinet C., Binart N., Kelly P.A. Genes Dev. 1997; 11, 167-178.