The insulin receptor-related receptor (IRR) demonstrates striking structural homology to the insulin receptor (IR) and insulin-like growth factor-I receptor (IGFR), suggesting that IRR is a member of the IR family. However, the endogenous ligand and biological role for this “orphan” receptor are unknown. To identify potential sites of action for the IRR, in situ hybridization was employed to reveal cellular patterns of IRR gene expression in the developing and adult rat and in the adult human kidney. From embryonic days 15-20, IRR mRNA is most abundant in sensory neurons of the trigeminal and dorsal root ganglia and, to a lesser extent, neurons of the autonomic system. IRR gene expression diminishes in the majority of sensory neurons postnatally, but remains abundant in a subpopulation of adult rat trigeminal and dorsal root ganglion neurons. IRR mRNA is localized in peripheral autonomic ganglia localized in the adrenal medulla and renal hilum in the adult. From birth to maturity, IRR mRNA is abundant in renal epithelial cells focally localized in the distal tubule in both rat and human kidney. The specificity of this pattern of IRR gene expression was demonstrated by hybridization of serial tissue sections with two different nonoverlapping cRNA probes. Nonspecific signal, as measured by IRR sense probe hybridization, was negligible. This highly restricted pattern of IRR gene expression is in marked contrast to the very widespread pattern of gene expression demonstrated by the IR and IGFR. This study showed that IRR, IR, and IGFR mRNAs were colocalized in some sensory neurons, suggesting the possibility for hybrid receptor formation in these cells. In summary, IRR gene expression is focally localized in sensory and autonomic neurons and renal distal tubule cells. These observations suggest that the IRR, in contrast to the related IR and IGFR, serves a narrow cell-specific role.
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