Endocrinology, Vol 130, 3237-3245, Copyright © 1992 by Endocrine Society

ARTICLES

Anatomical relationships in the patterns of insulin-like growth factor (IGF)-I, IGF binding protein-1, and IGF-I receptor gene expression in the rat kidney

E Chin, J Zhou and C Bondy
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

The rat kidney is both a target of circulating insulin-like growth factor-I (IGF-I) and a site of local IGF-I production. In order to identify which renal structures produce IGF-I and the functionally related IGF binding protein 1 (IGFBP-1), and which structures are potential sites of circulating or endogenous renal IGF action, we have employed in situ hybridization to localize IGF-I, IGFBP-1, and IGF-I receptor messenger RNAs (mRNAs) in the rat kidney. The effects of hypophysectomy (Hx) and GH replacement on renal IGF-I, IGFBP-1, and IGF- I receptor gene expression have also been evaluated. IGF-I and IGFBP-1 mRNAs are both localized in the epithelial cells of medullary thick ascending limbs (TALs) of Henle's loops in the normal rat kidney. IGF-I receptor mRNA is also abundant in TALs, but, in addition, is distributed throughout the distal nephron and collecting duct, and in the glomerulus, with lowest levels found in proximal tubules. Hx and GH treatment had complex effects on patterns of renal IGF-I and IGFBP-1 gene expression. In general, Hx resulted in decreased IGF-I and increased IGFBP-1 mRNA levels, and GH treatment produced the opposite effects, while IGF-I receptor mRNA levels were not significantly effected by either treatment. However, the most dramatic effect produced by the interruption of the pituitary-renal axis was the demonstration of reciprocal changes in IGF-I vs. IGFBP-1 gene expression in individual kidneys and even in individual nephrons, suggesting a local interaction between IGF-I and IGFBP-1 in the regulation of their respective mRNA levels. Functional implications issuing from these anatomical relationships in renal patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression are that IGF-I, if secreted into the tubular lumen, possibly carried or modulated by IGFBP-1, may act on luminal TAL and downstream receptor sites. The specific physiological role of IGF-I produced in TALs is open to speculation. Glomerular IGF-I receptor sites, based on their localization upstream and distant from local sources of IGF-I production, are predicted to be targets for circulating IGFs.

This article has been cited by other articles:

				H. Dimke, A. Flyvbjerg, S. Bourgeois, K. Thomsen, J. Frokiaer, P. Houillier, S. Nielsen, and S. Frische Acute growth hormone administration induces antidiuretic and antinatriuretic effects and increases phosphorylation of NKCC2 Am J Physiol Renal Physiol, February 1, 2007; 292(2): F723 - F735. [Abstract] [Full Text] [PDF]

				B. F. Schrijvers, A. S. De Vriese, and A. Flyvbjerg From Hyperglycemia to Diabetic Kidney Disease: The Role of Metabolic, Hemodynamic, Intracellular Factors and Growth Factors/Cytokines Endocr. Rev., December 1, 2004; 25(6): 971 - 1010. [Abstract] [Full Text] [PDF]

				Y. Wei, Y.-J. Chen, D. Li, R. Gu, and W.-H. Wang Dual effect of insulin-like growth factor on the apical 70-pS K channel in the thick ascending limb of rat kidney Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1258 - C1263. [Abstract] [Full Text] [PDF]

				Z. Symon, S. Fuchs, Y. Agmon, O. Weiss, I. Nephesh, R. Moshe, M. Brezis, A. Flyvbjerg, and I. Raz The endogenous insulin-like growth factor system in radiocontrast nephropathy Am J Physiol Renal Physiol, March 1, 1998; 274(3): F490 - F497. [Abstract] [Full Text] [PDF]

				A. Piron, I. Leonard, D. Nonclercq, G. Toubeau, P. Falmagne, J.-A. Heuson-Stiennon, and G. Laurent In vitro demonstration of a mitogenic activity in renal tissue extracts during regenerative hyperplasia Am J Physiol Renal Physiol, February 1, 1998; 274(2): F348 - F357. [Abstract] [Full Text] [PDF]

				B. Moreno, J. C. Rodriguez-Manzaneque, A. Perez-Castillo, and A. Santos Thyroid Hormone Controls the Expression of Insulin-Like Growth Factor I Receptor Gene at Different Levels in Lung and Heart of Developing and Adult Rats Endocrinology, March 1, 1997; 138(3): 1194 - 1203. [Abstract] [Full Text] [PDF]