GROWTH-HORMONE AND NUTRITION INTERACT TO REGULATE EXPRESSIONS OF KIDNEY IGF-I AND IGFBP MESSENGER-RNAS

The effects of growth hormone (GH) and fasting on renal insulin-like g rowth factor-I (IGF-I) and IGF-binding proteins (IGFBP)-1, -2, -3, -4, -5 were examined in spontaneous dwarf rats (SDR) which have a complet e and specific lack of GH among pituitary hormones. Renal expression o f 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 e xpression of IGF-I and IGFBP-1 mRNA, suggesting that GH is, among othe r pituitary hormones, more specifically associated with renal expressi on of these genes. The elevation in the IGFBP-4 mRNA level, however, w as not attenuated by GH administration, indicating that this hormone m ay not be directly related to the regulation of expression of this gen e. Fasting for 48 hours resulted in a reduction of IGF-I mRNA and an i ncrease 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 fa sting-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 reg ulated differently in different tissues. Based on our finding that IGF BP-1 modulates the mitogenic action of TGF-I, a full understanding of nutrition-related growth processes in the kidney must take this relati onship into consideration as well as that which exists between GH and IGF-I.