Growth hormone and nutrition interact to regulate expressions of kidney IGF-I and IGFBP mRNAs

Abstract

The effects of growth hormone (GH) and fasting on renal insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBP)-1, -2, -3, -4, -5 were examined in spontaneous dwarf rats (SDR) which have a complete and specific lack of GH among pituitary hormones. Renal expression of the mRNA which encodes IGF-I was reduced in these rats, and IGFBP-1 and IGFBP-4 were found to be elevated. Administration of GH restored expression of IGF-I and IGFBP-1 mRNA, suggesting that GH is, among other pituitary hormones, more specifically associated with renal expression of these genes. The elevation in the IGFBP-4 mRNA level, however, was not attenuated by GH administration, indicating that this hormone may not be directly related to the regulation of expression of this gene. Fasting for 48 hours resulted in a reduction of IGF-I mRNA and an increase in IGFBP-1 mRNA in SDRs as well as in normal rats, suggesting that a cause other than a reduced serum GH is responsible for these fasting-induced changes. Fasting resulted in little change in levels of other IGFBP-2, -3, -4, -5 mRNAs. When these results were compared with those obtained using liver, IGFBP mRNA expression was shown to be regulated differently in different tissues. Based on our finding that IGFBP-1 modulates the mitogenic action of IGF-I, a full understanding of nutrition-related growth processes in the kidney must take this relationship into consideration as well as that which exists between GH and IGF-I.